Procter Gamble Company Merger Case Study

Procter Gamble Company Merger Case Study The project deals with the analysis of mergers and acquisitions in an FMCG sector. Products which have a quick turnover, and relatively low cost are known as Fast Moving Consumer Goods (FMCG). FMCG products are those that get replaced within a year. A merger is the combining of two or more companies, generally by offering the stockholders of one company securities in the acquiring company in exchange for the surrender of their stock. This project deals with the merger of Procter Gamble and Gillette, acquisition of Balsaras hygiene and home product by Dabur and Acquisition of Nihar brand from HLL by Marico. The methodology deals with the various ways in which the data for this project was collected. Due to the limited scope of information and time constraints, secondary and not primary data sources has been used including journals, articles, reference sites, etc. The project guide proved very vital in the successful completion of my report. The next section deals with the individual introduction of both companies involved in the process of merger. It further includes the different terms of the merger and various synergies created through the merger. Furthermore the next section deals with scenario after the merger and analysis of financial statements of acquiring company post merger. Building a brand from scratch in the FMCG space can be quite an expensive exercise. Mature categories such as personal care or household products are already dominated by one or two strong incumbents and wresting market share away from them is quite a challenge. With growth rates in markets such as skin care, hair care and household products suddenly moving into high gear, companies also cannot afford to lose time on the trial-and-error method that usually accompanies new launches. Given this scenario, domestic players seem to view brand acquisitions and mergers as the quickest way to step into new categories and acquire a well-rounded product basket, without squandering their surpluses on brand-building expenses. Market shares apart, many of the buyouts have been motivated by the need to acquire better distribution reach whether within India or overseas. Introduction I. MERGER A merger is the combining of two or more companies, generally by offering the stockholders of one company securities in the acquiring company in exchange for the surrender of their stock. A merger occurs when two or more companies combines and the resulting firm maintains the identity of one of the firms. One or more companies may merge with an existing company or they may merge to form a new company. Usually the assets and liabilities of the smaller firms are merged into those of larger firms. Merger may take two forms- Merger through absorption Merger through consolidation. Absorption: Absorption is a combination of two or more companies into an existing company. All companies except one lose their identity in a merger through absorption. Consolidation: A consolidation is a combination if two or more combines into a new company. In this form of merger all companies are legally dissolved and a new entity is created. In consolidation the acquired company transfers its assets, liabilities and share of the acquiring company for cash or exchange of assets. II. ACQUISITION A fundamental characteristic of merger is that the acquiring company takes over the ownership of other companies and combines their operations with its own operations. An acquisition may be defined as an act of acquiring effective control by one company over the assets or management of another company without any combination of companies. III. TAKEOVER A takeover may also be defined as obtaining control over management of a company by another company.Merger of Procter Gamble Company and Gillette CompanyAbout the merging companies: Procter Gamble Procter Gamble Company is asoap opera. PG was named 2008 Advertiser of the Year by Cannes International Advertising Festival. Effective July 1, 2007, the companys operations are categorized into three Global Business Units with each Global Business Unit divided into Business Segments according to the companys March 2009 earnings release. Beauty Care Beauty segment Grooming segment Household Care Baby Care and Family Care segment Fabric Care and Home Care segment Health and Well-Being Health Care segment Snacks, Coffee, and Pet Care segment PG has gone into an aggressive mode. It has launched two new variants on 2nd Dec 2009, one in the detergent segment, which is called Tide Naturals and also another one in skin care segment under the Olay brand. Gillette Company The Gillette Company is a globally focused consumer products marketer that seeks competitive advantage in quality, value-added personal care and personal use products. It is the world leader in the mens grooming product category as well as in certain womens grooming products. Although more than half of company profits are still derived from shaving equipmentthe area in which the company startedGillette has also attained the top spots worldwide in writing instruments (Paper Mate, Parker, and Waterman brands) and correction products (Liquid Paper), toothbrushes and other oral care products (Oral-B), and alkaline batteries (Duracell products, which generate almost one-fourth of company profits). Gillette maintains 64 manufacturing facilities in 27 countries, and its products are sold in more than 200 countries and territories, with more than 60 percent of sales occurring outside the United States. The Merger: On October 1, 2005, Procter Gamble finalized its purchase of The Gillette Company. As a result of this merger, the Gillette Company no longer exists. Its last day of market trading symbol G on theOral-B, among others, which have also been maintained by PG. The Terms of the Merger: Date of merger: The merger came into effect from July 1st, 2007. The new company formed : The Gillette Companys assets were initially incorporated into a PG unit known internally as Global Gillette. In July 2007, Global Gillette was dissolved and incorporated into Procter Gambles other two main divisions, Procter Gamble Beauty and Procter Gamble Household Care. Gillettes brands and products were divided between the two accordingly. The Share Swap Ratio : Under the deal announced, Procter Gamble will pay 0.975 share of its common stock for each share of Gillette common stock. On Wall Street, shares in Gillette closed up nearly 13%, while PG slid 2.1% after the announcement. The Management: Gillettes chief executive James Kilts is to join the board of the merged company, becoming PG vice chairman, while PG chief executive A.G. Lafley will remain chief executive of the merged company. Examining the merger: Type of merger: Procter Gamble being number one in consumer products went into acquiring and merging with other companies like, Germanys Wella AG hair care line in 2003 and it also acquired Clairol for its hair-care lines and Iams Co. for its pet foods. The merger in question; between Procter Gamble and Gillette is thus a merger where the acquiring company is expanding in size of operations and also product offerings. This is thus a horizontal merger. Operational Synergies of the merger: The merger of the two companies will create the worlds largest consumer products conglomerate. Both companies are strong, diversified companies, so one wonders what uncaptured synergies there could be here. PG is adept at taking innovations from one product and transferring it to another product, so there may be opportunities to improve existing Gillette products. In addition, the companies are stating that the merger will give them more negotiating power with the most powerful buyer of consumer products. The deal would give the company even more control over shelf space at the nations retailers and grocers, real estate that is at a premium. Executives at the companies said they believe theyll both be able to grow faster together than separately, with PG opening doors for Gillette in markets such as China and Japan while Gillette bringing PG some product segments that are growing faster than the companys overall current portfolio of products.The merger will make PG the worlds biggest household goods maker, pushing Unilever into second place Financial Synergies: The merger would create a company with revenues of more than Rs.2700 billion that would have even greater clout against mass-market retailers like Wal-Mart Stores Inc., which have been pressuring consumer product suppliers to keep costs low. Because of expectations from the deal, PG raised the annual revenue growth outlook to 5 to 7 percent, rather than its earlier target of 4 to 6 percent. The companies said they expected cost savings and synergies of about Rs.630 billion to Rs.720 billion US over three years. PG and Gillettes combined market capitalization of about Rs 8325 billion US, would be by far the largest in the FMCG sector. HR Synergies: As part of the cost-cutting that would follow the deal, the merger would result in the elimination of about 6,000 jobs, or 4 percent of the combined work force of about 140,000. It said most of the cuts would come from eliminating management overlaps and consolidation of business support functions. Gillettes chief executive James Kilts is to join the board of the merged company, becoming PG vice chairman, while PG chief executive A.G. Lafley will remain chief executive of the merged company. Scenario Post Merger: Procter Gamble is the worlds largest producer of household and personal products by revenue, with its products reaching 4 billion people worldwide and its product line includes 23 brands across beauty, healthcare, and food including Tide detergent, Pampers diapers, and Gillette razors, that generate over $1 billion in revenue annually, with the companys total revenue at Rs.3555 billion in 2009.In 2005, PG expanded its portfolio to include razors and blades as well as batteries with its acquisition of the Gillette Company.The companys 2010 first quarter net income fell 1% to Rs.148.95 billion (Rs.46.35 per share) as higher prices offset lower sales volumes and foreign exchange effects, beating analyst expectations of Rs.43.65 per share. Revenue fell 6% to Rs.891.45 billion, though organic sales rose 2%. One of the key areas of growth for the company is in emerging markets worldwide. Sales in developing nations have increased steadily from 20% of total revenue in 2002 to 32% in 2009.PG already owns large and growing market share in countries includingglobal economic downturn, PG has announced it will focus its growth strategy on emerging markets, opening almost all of its 20 new manufacturing facilities outside its established markets. Procter Gamble attempts to maintain its competitive edge by focusing on product innovation. To this end, PG spends almost twice as much on research and development spending Rs.90 billion in 2009 as its closest competitor, Unilever, spent about Rs.58.5 billion USD in 2008.Through itsConnect + Developinitiative, PG looks to bring in new product ideas from outside the company. Connect + Develop has led to the development of 42% of new PG products in recent years. In fiscal 2009, PGs Net sales fell 3% to Rs.3555 billion driven by a 3% decline in unit volume and a 4% decline in net sales from the rising US dollar. Organic sales, a closely watched figure which excludes the impact of acquisitions, divestitures, andforeign exchange, increased 2%, which is below its target organic sales range of 4-6%.Earnings for fiscal 2009 increased 11% to Rs.603 billion. In July 2009, CEO A.G. Lafley stepped down from his post after 29 years with Proctor Gamble.He was succeeded by current COO Bob McDonald.The company expects sales to be up 0 to 3% in fiscal 2010,with sales back up in the fall of 2009, fed by price cuts, new products, and value-focused promotions. PG divides its business into three Global Business Units (GBUs) that develop and produce products and its corporate group which handles the operation and administration of the company. Beauty (33% of 2009 sales, 36% of 2009 net income): The Beauty GBU includes all hair and skin products, medications, razors, electric shavers, and batteries. This business unit includes several product lines acquired when the PG bought consumer products company Gillette in 2005. Proctor Gambles global market share in blades and razors is 70%, primarily centered on its Mach3, Fusion, Venus, and Gillette brands.In June 2009, PG further expanded its mens grooming business with the acquisition of the high-end shaving company The Art of Shaving and the mens skin care line Zirh. Health and Well-Being (21% of 2009 sales, 24% of 2009 net income): The Health and Well-Being GBU provide oral care, feminine health, pharmaceuticals, snacks, coffee, and pet care products. In oral care, the company has the number two market share position at 20% globally.In potato chips, the companys Pringles brand holds a market share of approximately 10%. Household Care (46.8% of 2009 sales, 43% of 2009 net income): The Household Care GBU manufactures a wide range of products from laundry detergent to diapers. The companys baby care market share in 2008 was 29%. Business Growth and Divestitures Folgers Sale On June 4, 2008, PG sold its Folgers coffee unit toJ.M. Smucker Companyfor Rs.132.75 billion.As part of the deal, PG shareholders will receive a 53.5 percent stake in Smuckers and the company will assume Rs.15750 million of Folgers debt. Gillette Acquisition Procter Gamble acquired Gillette in 2005 for over Rs.2250 billion in its largest acquisition to date. In 2004, the last full year before the acquisition, Gillette generated over Rs.450 billion in sales, about Rs.270 billion of which came from razors and Duracell and Braun products and the remainder sourced from the Oral-B brand, which was moved into the Health Well-Being segment. A key piece of the acquisition beyond Gillettes product lines was its distribution network and supply chain. Gillettes distribution network and supply chain in emerging markets had been extremely successful for Gillette and, once acquired, has worked to complement PGs own distribution network. Sale of Pharmaceutical Unit In 2009 PG sold its pharmaceutical unit to Warner Chilcott Plc for Rs.139.5 billion in cash.The company expects to book a 43 cent per share earnings boost in Q2 of fiscal 2010 as a result of the sale.The deal allows PG to focus on its personal care, beauty, and household product divisions. In 2006, the company started winding down its discover-phase pharmaceutical products in favor of licensing late-stage compounds, and announced in 2008 it would exit the drug industry entirely. PG 2008 Net sales by Geographic Region(Post merger) PG has a well-established market presence in developed countries such as the United States and Western Europe and is looking to its presence in emerging markets. In fiscal 2009, 32% of total net sales came from developing nations,a figure that has increased steadily from 2002 when sales in developing nations accounted for only about 20% of total revenue (approximately Rs.360 billion). In China and Russia, PGs market share has been consistently increasing in the past five years as Procter Gamble has put an increased emphasis on establishing its products in those markets. In 2008, the companys distribution network reached 800 million people in China and 80% of the population in Russia. PG has created products designed specifically to target developing nations. The average Mexican spends about Rs.9000 a year on PG products, Chinese per-capita spending is only about Rs.135 and India per-capita spending Rs.45.Increasing sales in China and India to the levels in Mexico would add Rs.1800 billion in sales to the companys overall revenue. Research Development focuses both inside and outside the company In 2009, PG spent approximately Rs.91.8 billion on Research Development, nearly Rs.45 billion more than its closest competitor, Unilever.The two most important factors in PGs innovation process are its practice of consumer demand research and its Connect and Develop RD structure. First, when entering new markets, PG sets up in-home visits with consumers in order to fully understand the needs and desires consumers have for household and personal products. This way, PG gets directly to its customers and is able to cater to their needs. PG also incorporates consumers input into the RD process through its Connect and Develop initiative. Through Connect and Develop PG has an online interface set up where people can submit product ideas and provide input on topics that PG places on the web-portal. PG staff then sorts through the ideas and work with the most promising ones. This process is not responsible for the entire RD that PG does, but approximately 42% of new products in the last sev eral years were influenced by or originated from Connect and Develop. Tide Stain Release, a stain-removing detergent released in July 2009, has garnered 10% market share in the US as of November 2009.The Bounce Dryer Bar, an automatic laundry freshener released in August 2009, has captured 7% of the North American fabric sheet market as of November 2009. Commodity Prices A diversified consumer products manufacturer, PG depends heavily on a wide basket of global commodities for manufacturing its goods, the prices for which have risen nearly 50% since 2002. Nearly half of the companys cost of goods is directly related to commodity goods. The company has increased prices due to higher costs of oil and other raw materials. In its conference call, the company stated that it expected raw material costs to increase Rs.135 billion in 2009.The company has raised prices on Cascade dishwashing detergent, Iams pet food, and Gillette razors to counter the increasing cost of oil in the first half of 2008.PG instituted broad price adjustments in Q1 2010 to close widening price gaps in several businessesincluding North American laundry, tissue, andtowel, and several Eastern European markets. Competition Procter Gamble provides the broadest and biggest portfolio of products in the household and personal care industry with 24 billion-dollar brands. PG generates 43% more revenue than its closest competitor,LOreal, and Reckitt Benckiser. Here are somekey factsabout the two firms. Cincinnati-based Procter Gamble was established in 1837 and made its name selling soap and candles to U.S. government soldiers during the civil war. Boston-based Gillette spends around Rs.2700 million annually on advertising. In May the razor-maker paid a reported 40 million pounds (Rs.3393 million) to sign international soccer star David Beckham to a three-year deal as its global face. Procter Gamble employs a workforce of 110,000 worldwide and has a market capitalization of Rs.6345 billion. Gillette employs 29,400 employees worldwide and has a market capitalization of Rs.2025 billion. Gillettes profit beat market expectations last October after Hurricane Ivan spurred the buying of Duracell batteries. Limitations: Due to lack of data the financial statements analysis of Procter Gamble was not carried out. Conclusion Thus the acquisition and integration of Gillette was the largest and most successful in the history of Procter Gamble. PG acquired Gillette, which is best known for its shaving products, in 2005 for Rs.2565 billion. The merger between Procter Gamble and Gillette is a horizontal merger where the acquiring company is expanding in size of operations and also product offerings. The merger created various synergies like financial, operation and human resource synergies. After the merger Procter Gamble integrated systems in 26 countries, spanning five geographic regions, representing about 20% of sales. Gillette is a catalyst that makes PG a better brand-builder and a stronger innovation leader. There is no doubt that PG and Gillette are stronger together than alone, and both the companies together can deliver accelerated growth targets over the balance of the decade. Acquisition of Balsarashygiene and home product by Dabur About the merging companies: Dabur Company Dabur India Limitedis the fourth largest FMCG Company in India and Dabur had a turnover of approximately Rs.2,834 Crore Market Capitalisation of over Rs 10,000 Crore, with brands like Dabur Amla, Dabur Chyawanprash, Vatika, Hajmola and Real. The company has kept an eye on new generations of customers with a range of products that cater to a modern lifestyle, while managing not to alienate earlier generations of loyal customers. Dabur has global presence in 50 countries; products are available in the markets of Middle East, South-East Asia, Africa, the European Union andAmerica. Dabur is an investor friendly brand as its financial performance shows. The companys growth rate rose from 10% to 40%. The expected growth rate for two years was two-fold. Theres a great sense of responsibility for investors funds on view. This is a direct extension of Daburs philosophy of taking care of its constituents and it adds to the sense of trust for the brand overall. The company, through Dabur Pharma Ltd. does toxicology tests and markets ayurvedic medicines in a scientific manner. They have researched new medicines which will find use in O.T. all over the country therein opening a new market. Dabur Foods, a subsidiary of Dabur India is expecting to grow at 25%. Its brands of juices, namely, Real and Active, together make it the market leader in the Fruit Juice Category. Dabur Ranked AmongIndias Most Trusted Brands of 2007 By Economic Times-Brand Equity. Products of Dabur Ø Under health care products it has brands like Hajmola, Pudin Hara, Dabur Chyawanprash, Glucose D, Dabur Lal tail,etc. Ø In home care range consist of product like Odinil,Odomos,odopic,etc. Ø Under personal care range it has product like Vatika,Gulabri,Dabur Red Toothpaste,etc. Ø In food range it has brands like Real Active ,HOMMADE-range of ready made pastes, soups, coconut milk tomato puree Ø Dabur has guar gum plant,a natural gum used in foods industrial applications. Ø Dabur also produces ayurvedic medicines. Balsara Company The Balsara Group manufactures and markets its products, in India and Internationally. The Group has a domestic annual sales turnover of Indian Rs. 2 billion, and a rapidly growing international sales turnover of Indian Rs. 350 million. The Group is professionally managed, with manufacturing, sales, distribution and administrative facilities located throughout India, in addition to its international operations. In the Indian market, 60% of the Balsara Groups sales turnover of Indian Rs. 2 billion comes from Personal Hygiene Products (Promise, Babool and Meswak oral care ranges) and 40% is derived from Household Products (Odomos insect repellents, Odonil Air Fresheners, Sani Fresh toilet cleaners and Odopic dish washing products). Balsara has a wide national sales and distribution system that makes products available in 10, 54,000 retail outlets. The system is supported by a distribution network of 4 Zonal Offices, 13 Branches, 24 Regional Warehouses, and 1700 Distributors in 1500 towns. The mission of the Balsara Group of Companies is to be a leading provider of superior quality personal and household products, ingredients and packaging materials to consumers and customers on the Indian sub-continent and throughout the world. The Acquisition: On January 27, 2005 Dabur India today announced the acquisition of Balsara Hygeine and Home Care businesses for Rs. 143 crores and said it would look at more buyouts to capitalise on the consolidation in the sector. The company board of Dabur approved the acquisition of controlling stake in three Balsara group companies Balsara Hygiene Products, Balsara Home Products and Besta Cosmectics. With the acquisition of the Rs. 143-crore Balsara Group in an all cash deal, Dabur India will have oral care brands such as Promise, Babool, Meswak; mosquito repellents such as Odomos and household products such as Odonil and Odopic under its fold. Dabur India will acquire the entire promoters stake in the three companies 99.4 per cent in Balsara Hygiene, 100 per cent in Balsara Home Products and 97.9 per cent in Besta Cosmetics. The Terms of the Acquisition: Date of the acquisition: The merger came into effect from 1st April 2006. The new company formed : According to the deal Dabur will take full control of Balsaras entire brand portfolio which consists of oral care brands like Promise, Babool, Meswak; mosquito repellants like Odomos and household products like Odonil, Odopic. The deal also includes takeover of Balsaras operations consisting of three manufacturing facilities at Kanpur, Silvassa and Baddi and about 600 employees. Dabur India will also acquire the entire promoters stake in the three companies 99.4 per cent in Balsara Hygiene, 100 per cent in Balsara Home Products and 97.9 per cent in Besta Cosmetics. The Share Swap Ratio : Under the deal announced, Dabur India Ltd will acquire Balsaras hygiene and home product businesses in an Rs 143 crore all-cash deal. While Rs 120 crore will be funded through internal accruals, the balance Rs 23 crore will be raised through debt. Examining the Acquisition: Type of merger: The Rs 1,300-crore fast-moving consumer goods major Dabur India acquired Mum Procter Gamble Company Merger Case Study Procter Gamble Company Merger Case Study The project deals with the analysis of mergers and acquisitions in an FMCG sector. Products which have a quick turnover, and relatively low cost are known as Fast Moving Consumer Goods (FMCG). FMCG products are those that get replaced within a year. A merger is the combining of two or more companies, generally by offering the stockholders of one company securities in the acquiring company in exchange for the surrender of their stock. This project deals with the merger of Procter Gamble and Gillette, acquisition of Balsaras hygiene and home product by Dabur and Acquisition of Nihar brand from HLL by Marico. The methodology deals with the various ways in which the data for this project was collected. Due to the limited scope of information and time constraints, secondary and not primary data sources has been used including journals, articles, reference sites, etc. The project guide proved very vital in the successful completion of my report. The next section deals with the individual introduction of both companies involved in the process of merger. It further includes the different terms of the merger and various synergies created through the merger. Furthermore the next section deals with scenario after the merger and analysis of financial statements of acquiring company post merger. Building a brand from scratch in the FMCG space can be quite an expensive exercise. Mature categories such as personal care or household products are already dominated by one or two strong incumbents and wresting market share away from them is quite a challenge. With growth rates in markets such as skin care, hair care and household products suddenly moving into high gear, companies also cannot afford to lose time on the trial-and-error method that usually accompanies new launches. Given this scenario, domestic players seem to view brand acquisitions and mergers as the quickest way to step into new categories and acquire a well-rounded product basket, without squandering their surpluses on brand-building expenses. Market shares apart, many of the buyouts have been motivated by the need to acquire better distribution reach whether within India or overseas. Introduction I. MERGER A merger is the combining of two or more companies, generally by offering the stockholders of one company securities in the acquiring company in exchange for the surrender of their stock. A merger occurs when two or more companies combines and the resulting firm maintains the identity of one of the firms. One or more companies may merge with an existing company or they may merge to form a new company. Usually the assets and liabilities of the smaller firms are merged into those of larger firms. Merger may take two forms- Merger through absorption Merger through consolidation. Absorption: Absorption is a combination of two or more companies into an existing company. All companies except one lose their identity in a merger through absorption. Consolidation: A consolidation is a combination if two or more combines into a new company. In this form of merger all companies are legally dissolved and a new entity is created. In consolidation the acquired company transfers its assets, liabilities and share of the acquiring company for cash or exchange of assets. II. ACQUISITION A fundamental characteristic of merger is that the acquiring company takes over the ownership of other companies and combines their operations with its own operations. An acquisition may be defined as an act of acquiring effective control by one company over the assets or management of another company without any combination of companies. III. TAKEOVER A takeover may also be defined as obtaining control over management of a company by another company.Merger of Procter Gamble Company and Gillette CompanyAbout the merging companies: Procter Gamble Procter Gamble Company is asoap opera. PG was named 2008 Advertiser of the Year by Cannes International Advertising Festival. Effective July 1, 2007, the companys operations are categorized into three Global Business Units with each Global Business Unit divided into Business Segments according to the companys March 2009 earnings release. Beauty Care Beauty segment Grooming segment Household Care Baby Care and Family Care segment Fabric Care and Home Care segment Health and Well-Being Health Care segment Snacks, Coffee, and Pet Care segment PG has gone into an aggressive mode. It has launched two new variants on 2nd Dec 2009, one in the detergent segment, which is called Tide Naturals and also another one in skin care segment under the Olay brand. Gillette Company The Gillette Company is a globally focused consumer products marketer that seeks competitive advantage in quality, value-added personal care and personal use products. It is the world leader in the mens grooming product category as well as in certain womens grooming products. Although more than half of company profits are still derived from shaving equipmentthe area in which the company startedGillette has also attained the top spots worldwide in writing instruments (Paper Mate, Parker, and Waterman brands) and correction products (Liquid Paper), toothbrushes and other oral care products (Oral-B), and alkaline batteries (Duracell products, which generate almost one-fourth of company profits). Gillette maintains 64 manufacturing facilities in 27 countries, and its products are sold in more than 200 countries and territories, with more than 60 percent of sales occurring outside the United States. The Merger: On October 1, 2005, Procter Gamble finalized its purchase of The Gillette Company. As a result of this merger, the Gillette Company no longer exists. Its last day of market trading symbol G on theOral-B, among others, which have also been maintained by PG. The Terms of the Merger: Date of merger: The merger came into effect from July 1st, 2007. The new company formed : The Gillette Companys assets were initially incorporated into a PG unit known internally as Global Gillette. In July 2007, Global Gillette was dissolved and incorporated into Procter Gambles other two main divisions, Procter Gamble Beauty and Procter Gamble Household Care. Gillettes brands and products were divided between the two accordingly. The Share Swap Ratio : Under the deal announced, Procter Gamble will pay 0.975 share of its common stock for each share of Gillette common stock. On Wall Street, shares in Gillette closed up nearly 13%, while PG slid 2.1% after the announcement. The Management: Gillettes chief executive James Kilts is to join the board of the merged company, becoming PG vice chairman, while PG chief executive A.G. Lafley will remain chief executive of the merged company. Examining the merger: Type of merger: Procter Gamble being number one in consumer products went into acquiring and merging with other companies like, Germanys Wella AG hair care line in 2003 and it also acquired Clairol for its hair-care lines and Iams Co. for its pet foods. The merger in question; between Procter Gamble and Gillette is thus a merger where the acquiring company is expanding in size of operations and also product offerings. This is thus a horizontal merger. Operational Synergies of the merger: The merger of the two companies will create the worlds largest consumer products conglomerate. Both companies are strong, diversified companies, so one wonders what uncaptured synergies there could be here. PG is adept at taking innovations from one product and transferring it to another product, so there may be opportunities to improve existing Gillette products. In addition, the companies are stating that the merger will give them more negotiating power with the most powerful buyer of consumer products. The deal would give the company even more control over shelf space at the nations retailers and grocers, real estate that is at a premium. Executives at the companies said they believe theyll both be able to grow faster together than separately, with PG opening doors for Gillette in markets such as China and Japan while Gillette bringing PG some product segments that are growing faster than the companys overall current portfolio of products.The merger will make PG the worlds biggest household goods maker, pushing Unilever into second place Financial Synergies: The merger would create a company with revenues of more than Rs.2700 billion that would have even greater clout against mass-market retailers like Wal-Mart Stores Inc., which have been pressuring consumer product suppliers to keep costs low. Because of expectations from the deal, PG raised the annual revenue growth outlook to 5 to 7 percent, rather than its earlier target of 4 to 6 percent. The companies said they expected cost savings and synergies of about Rs.630 billion to Rs.720 billion US over three years. PG and Gillettes combined market capitalization of about Rs 8325 billion US, would be by far the largest in the FMCG sector. HR Synergies: As part of the cost-cutting that would follow the deal, the merger would result in the elimination of about 6,000 jobs, or 4 percent of the combined work force of about 140,000. It said most of the cuts would come from eliminating management overlaps and consolidation of business support functions. Gillettes chief executive James Kilts is to join the board of the merged company, becoming PG vice chairman, while PG chief executive A.G. Lafley will remain chief executive of the merged company. Scenario Post Merger: Procter Gamble is the worlds largest producer of household and personal products by revenue, with its products reaching 4 billion people worldwide and its product line includes 23 brands across beauty, healthcare, and food including Tide detergent, Pampers diapers, and Gillette razors, that generate over $1 billion in revenue annually, with the companys total revenue at Rs.3555 billion in 2009.In 2005, PG expanded its portfolio to include razors and blades as well as batteries with its acquisition of the Gillette Company.The companys 2010 first quarter net income fell 1% to Rs.148.95 billion (Rs.46.35 per share) as higher prices offset lower sales volumes and foreign exchange effects, beating analyst expectations of Rs.43.65 per share. Revenue fell 6% to Rs.891.45 billion, though organic sales rose 2%. One of the key areas of growth for the company is in emerging markets worldwide. Sales in developing nations have increased steadily from 20% of total revenue in 2002 to 32% in 2009.PG already owns large and growing market share in countries includingglobal economic downturn, PG has announced it will focus its growth strategy on emerging markets, opening almost all of its 20 new manufacturing facilities outside its established markets. Procter Gamble attempts to maintain its competitive edge by focusing on product innovation. To this end, PG spends almost twice as much on research and development spending Rs.90 billion in 2009 as its closest competitor, Unilever, spent about Rs.58.5 billion USD in 2008.Through itsConnect + Developinitiative, PG looks to bring in new product ideas from outside the company. Connect + Develop has led to the development of 42% of new PG products in recent years. In fiscal 2009, PGs Net sales fell 3% to Rs.3555 billion driven by a 3% decline in unit volume and a 4% decline in net sales from the rising US dollar. Organic sales, a closely watched figure which excludes the impact of acquisitions, divestitures, andforeign exchange, increased 2%, which is below its target organic sales range of 4-6%.Earnings for fiscal 2009 increased 11% to Rs.603 billion. In July 2009, CEO A.G. Lafley stepped down from his post after 29 years with Proctor Gamble.He was succeeded by current COO Bob McDonald.The company expects sales to be up 0 to 3% in fiscal 2010,with sales back up in the fall of 2009, fed by price cuts, new products, and value-focused promotions. PG divides its business into three Global Business Units (GBUs) that develop and produce products and its corporate group which handles the operation and administration of the company. Beauty (33% of 2009 sales, 36% of 2009 net income): The Beauty GBU includes all hair and skin products, medications, razors, electric shavers, and batteries. This business unit includes several product lines acquired when the PG bought consumer products company Gillette in 2005. Proctor Gambles global market share in blades and razors is 70%, primarily centered on its Mach3, Fusion, Venus, and Gillette brands.In June 2009, PG further expanded its mens grooming business with the acquisition of the high-end shaving company The Art of Shaving and the mens skin care line Zirh. Health and Well-Being (21% of 2009 sales, 24% of 2009 net income): The Health and Well-Being GBU provide oral care, feminine health, pharmaceuticals, snacks, coffee, and pet care products. In oral care, the company has the number two market share position at 20% globally.In potato chips, the companys Pringles brand holds a market share of approximately 10%. Household Care (46.8% of 2009 sales, 43% of 2009 net income): The Household Care GBU manufactures a wide range of products from laundry detergent to diapers. The companys baby care market share in 2008 was 29%. Business Growth and Divestitures Folgers Sale On June 4, 2008, PG sold its Folgers coffee unit toJ.M. Smucker Companyfor Rs.132.75 billion.As part of the deal, PG shareholders will receive a 53.5 percent stake in Smuckers and the company will assume Rs.15750 million of Folgers debt. Gillette Acquisition Procter Gamble acquired Gillette in 2005 for over Rs.2250 billion in its largest acquisition to date. In 2004, the last full year before the acquisition, Gillette generated over Rs.450 billion in sales, about Rs.270 billion of which came from razors and Duracell and Braun products and the remainder sourced from the Oral-B brand, which was moved into the Health Well-Being segment. A key piece of the acquisition beyond Gillettes product lines was its distribution network and supply chain. Gillettes distribution network and supply chain in emerging markets had been extremely successful for Gillette and, once acquired, has worked to complement PGs own distribution network. Sale of Pharmaceutical Unit In 2009 PG sold its pharmaceutical unit to Warner Chilcott Plc for Rs.139.5 billion in cash.The company expects to book a 43 cent per share earnings boost in Q2 of fiscal 2010 as a result of the sale.The deal allows PG to focus on its personal care, beauty, and household product divisions. In 2006, the company started winding down its discover-phase pharmaceutical products in favor of licensing late-stage compounds, and announced in 2008 it would exit the drug industry entirely. PG 2008 Net sales by Geographic Region(Post merger) PG has a well-established market presence in developed countries such as the United States and Western Europe and is looking to its presence in emerging markets. In fiscal 2009, 32% of total net sales came from developing nations,a figure that has increased steadily from 2002 when sales in developing nations accounted for only about 20% of total revenue (approximately Rs.360 billion). In China and Russia, PGs market share has been consistently increasing in the past five years as Procter Gamble has put an increased emphasis on establishing its products in those markets. In 2008, the companys distribution network reached 800 million people in China and 80% of the population in Russia. PG has created products designed specifically to target developing nations. The average Mexican spends about Rs.9000 a year on PG products, Chinese per-capita spending is only about Rs.135 and India per-capita spending Rs.45.Increasing sales in China and India to the levels in Mexico would add Rs.1800 billion in sales to the companys overall revenue. Research Development focuses both inside and outside the company In 2009, PG spent approximately Rs.91.8 billion on Research Development, nearly Rs.45 billion more than its closest competitor, Unilever.The two most important factors in PGs innovation process are its practice of consumer demand research and its Connect and Develop RD structure. First, when entering new markets, PG sets up in-home visits with consumers in order to fully understand the needs and desires consumers have for household and personal products. This way, PG gets directly to its customers and is able to cater to their needs. PG also incorporates consumers input into the RD process through its Connect and Develop initiative. Through Connect and Develop PG has an online interface set up where people can submit product ideas and provide input on topics that PG places on the web-portal. PG staff then sorts through the ideas and work with the most promising ones. This process is not responsible for the entire RD that PG does, but approximately 42% of new products in the last sev eral years were influenced by or originated from Connect and Develop. Tide Stain Release, a stain-removing detergent released in July 2009, has garnered 10% market share in the US as of November 2009.The Bounce Dryer Bar, an automatic laundry freshener released in August 2009, has captured 7% of the North American fabric sheet market as of November 2009. Commodity Prices A diversified consumer products manufacturer, PG depends heavily on a wide basket of global commodities for manufacturing its goods, the prices for which have risen nearly 50% since 2002. Nearly half of the companys cost of goods is directly related to commodity goods. The company has increased prices due to higher costs of oil and other raw materials. In its conference call, the company stated that it expected raw material costs to increase Rs.135 billion in 2009.The company has raised prices on Cascade dishwashing detergent, Iams pet food, and Gillette razors to counter the increasing cost of oil in the first half of 2008.PG instituted broad price adjustments in Q1 2010 to close widening price gaps in several businessesincluding North American laundry, tissue, andtowel, and several Eastern European markets. Competition Procter Gamble provides the broadest and biggest portfolio of products in the household and personal care industry with 24 billion-dollar brands. PG generates 43% more revenue than its closest competitor,LOreal, and Reckitt Benckiser. Here are somekey factsabout the two firms. Cincinnati-based Procter Gamble was established in 1837 and made its name selling soap and candles to U.S. government soldiers during the civil war. Boston-based Gillette spends around Rs.2700 million annually on advertising. In May the razor-maker paid a reported 40 million pounds (Rs.3393 million) to sign international soccer star David Beckham to a three-year deal as its global face. Procter Gamble employs a workforce of 110,000 worldwide and has a market capitalization of Rs.6345 billion. Gillette employs 29,400 employees worldwide and has a market capitalization of Rs.2025 billion. Gillettes profit beat market expectations last October after Hurricane Ivan spurred the buying of Duracell batteries. Limitations: Due to lack of data the financial statements analysis of Procter Gamble was not carried out. Conclusion Thus the acquisition and integration of Gillette was the largest and most successful in the history of Procter Gamble. PG acquired Gillette, which is best known for its shaving products, in 2005 for Rs.2565 billion. The merger between Procter Gamble and Gillette is a horizontal merger where the acquiring company is expanding in size of operations and also product offerings. The merger created various synergies like financial, operation and human resource synergies. After the merger Procter Gamble integrated systems in 26 countries, spanning five geographic regions, representing about 20% of sales. Gillette is a catalyst that makes PG a better brand-builder and a stronger innovation leader. There is no doubt that PG and Gillette are stronger together than alone, and both the companies together can deliver accelerated growth targets over the balance of the decade. Acquisition of Balsarashygiene and home product by Dabur About the merging companies: Dabur Company Dabur India Limitedis the fourth largest FMCG Company in India and Dabur had a turnover of approximately Rs.2,834 Crore Market Capitalisation of over Rs 10,000 Crore, with brands like Dabur Amla, Dabur Chyawanprash, Vatika, Hajmola and Real. The company has kept an eye on new generations of customers with a range of products that cater to a modern lifestyle, while managing not to alienate earlier generations of loyal customers. Dabur has global presence in 50 countries; products are available in the markets of Middle East, South-East Asia, Africa, the European Union andAmerica. Dabur is an investor friendly brand as its financial performance shows. The companys growth rate rose from 10% to 40%. The expected growth rate for two years was two-fold. Theres a great sense of responsibility for investors funds on view. This is a direct extension of Daburs philosophy of taking care of its constituents and it adds to the sense of trust for the brand overall. The company, through Dabur Pharma Ltd. does toxicology tests and markets ayurvedic medicines in a scientific manner. They have researched new medicines which will find use in O.T. all over the country therein opening a new market. Dabur Foods, a subsidiary of Dabur India is expecting to grow at 25%. Its brands of juices, namely, Real and Active, together make it the market leader in the Fruit Juice Category. Dabur Ranked AmongIndias Most Trusted Brands of 2007 By Economic Times-Brand Equity. Products of Dabur Ø Under health care products it has brands like Hajmola, Pudin Hara, Dabur Chyawanprash, Glucose D, Dabur Lal tail,etc. Ø In home care range consist of product like Odinil,Odomos,odopic,etc. Ø Under personal care range it has product like Vatika,Gulabri,Dabur Red Toothpaste,etc. Ø In food range it has brands like Real Active ,HOMMADE-range of ready made pastes, soups, coconut milk tomato puree Ø Dabur has guar gum plant,a natural gum used in foods industrial applications. Ø Dabur also produces ayurvedic medicines. Balsara Company The Balsara Group manufactures and markets its products, in India and Internationally. The Group has a domestic annual sales turnover of Indian Rs. 2 billion, and a rapidly growing international sales turnover of Indian Rs. 350 million. The Group is professionally managed, with manufacturing, sales, distribution and administrative facilities located throughout India, in addition to its international operations. In the Indian market, 60% of the Balsara Groups sales turnover of Indian Rs. 2 billion comes from Personal Hygiene Products (Promise, Babool and Meswak oral care ranges) and 40% is derived from Household Products (Odomos insect repellents, Odonil Air Fresheners, Sani Fresh toilet cleaners and Odopic dish washing products). Balsara has a wide national sales and distribution system that makes products available in 10, 54,000 retail outlets. The system is supported by a distribution network of 4 Zonal Offices, 13 Branches, 24 Regional Warehouses, and 1700 Distributors in 1500 towns. The mission of the Balsara Group of Companies is to be a leading provider of superior quality personal and household products, ingredients and packaging materials to consumers and customers on the Indian sub-continent and throughout the world. The Acquisition: On January 27, 2005 Dabur India today announced the acquisition of Balsara Hygeine and Home Care businesses for Rs. 143 crores and said it would look at more buyouts to capitalise on the consolidation in the sector. The company board of Dabur approved the acquisition of controlling stake in three Balsara group companies Balsara Hygiene Products, Balsara Home Products and Besta Cosmectics. With the acquisition of the Rs. 143-crore Balsara Group in an all cash deal, Dabur India will have oral care brands such as Promise, Babool, Meswak; mosquito repellents such as Odomos and household products such as Odonil and Odopic under its fold. Dabur India will acquire the entire promoters stake in the three companies 99.4 per cent in Balsara Hygiene, 100 per cent in Balsara Home Products and 97.9 per cent in Besta Cosmetics. The Terms of the Acquisition: Date of the acquisition: The merger came into effect from 1st April 2006. The new company formed : According to the deal Dabur will take full control of Balsaras entire brand portfolio which consists of oral care brands like Promise, Babool, Meswak; mosquito repellants like Odomos and household products like Odonil, Odopic. The deal also includes takeover of Balsaras operations consisting of three manufacturing facilities at Kanpur, Silvassa and Baddi and about 600 employees. Dabur India will also acquire the entire promoters stake in the three companies 99.4 per cent in Balsara Hygiene, 100 per cent in Balsara Home Products and 97.9 per cent in Besta Cosmetics. The Share Swap Ratio : Under the deal announced, Dabur India Ltd will acquire Balsaras hygiene and home product businesses in an Rs 143 crore all-cash deal. While Rs 120 crore will be funded through internal accruals, the balance Rs 23 crore will be raised through debt. Examining the Acquisition: Type of merger: The Rs 1,300-crore fast-moving consumer goods major Dabur India acquired Mum

Hydrogels for Wound Healing Applications

Hydrogels for Wound Healing Applications Abstract This chapter discusses about the hydrogels both natural and synthetic that can be used for wound healing applications. Also it discusses briefly about the various novel techniques that have been developed recently. Keywords: Hydrogels; Chitosan, Antimicrobial; Grafting; Blending; Wound dressing; Wound healing; Gene therapy, Stem cell therapy, Skin Engineering, pH and Thermosensitive polymers. 1 Introduction Healthcare is an essential aspect of human survival. So many biopolymers have generated interest in a number of biomedical applications. Wound management is one such area where management of cuts, ulcers, and sores needs dressings which help in promoting rapid wound healing in order to obtain both functional and cosmetic results. [45] There are different kinds of wound management products: staples or sutures, dressings or bandages, surgical sealants and adhesives, skin substitutes, and other biomaterials. [51] Human skin provides an effective barrier to microbial penetration and subsequent infection. However, once the wound has been developed in this barrier, the infection chances increases. In case of chronic wounds, the colonization and infection potential increases as the result of the presence of avascular eschar which provides an environment for the uninhibited growth of microorganisms. [89] The rate of infection is related to the type of wound, general wound care, and local health of the patient. [88, 90] For avoiding infection, good clinical practices are needed. The management of chronic wounds is a very costly practice and it also places an enormous drain on healthcare resources; studies have calculated the cost of wounds to the NHS to be about  £1bn a year. [166] So for lowering this cost such wound management products are needed that are more economical and effective. Out of all the above wound management products, here in this chapter we will discuss more about the wound dressings that will provide an optimal healing environment to the wound. A dressing is an adjunct used by a person for application to a wound in order to promote healing and/or prevent further harm. It is designed to be in direct contact with the wound, so it is different from the bandage in the manner that bandages are normally used to hold dressing in place. A wound is a break in the epithelial integrity of the skin and may be accompanied by disruption of the structure and function of underlying normal tissue. Wounds can be divided into four categories based on their appearance and stage of healing: Necrotic, sloughing, granulating and epithelializing wounds. [87] Wounds cause discomfort and are more prone to infection and other troublesome complications. [75] Some diseases like diabetes, ischaemia and conditions like malnourishment, ageing, local infection, local tissue damage due to burn leads to delay in wound healing. Infection is a major complication of burn injury and is responsible for 50-75% of hospital deaths. [76] Human skin has one of the greatest capacities to regenerate itself amongst all of the tissues in our body. It constantly replaces old cells with new cells, enabling it to repair itself when damaged. Wound healing is a complex-physiologic process, which consists of three overlapping phases: inflammatory, proliferative and remodeling phases. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors. During the inflammation process, neutrophils are the first leukocytes which come at the site of injury to rid it from bacterial contamination. Then, the monocytes and their conversion to macrophages initiate tissue repair by releasing a number of biologically active substances and growth factors that are necessary for the initi ation of tissue formation process. In the third process, fibroblasts proliferate and migrate into the wound space and started the deposition of the loose extracellular matrix. Endothelial cells grow into a wound simultaneously with fibroblasts and undergo angiogenesis. Finally, tissue remodeling takes place to reconstruct the basement membrane by the differentiation of keratinocytes as well as the formation of follicle cells. [43, 49, 50] A scar is an essential part of this natural healing process following any type of damage to the skin. This can occur after a surgical incision or the healing of a wound. As your body makes an effort to close an open wound and protect itself from infection, it replaces injured skin tissue with rapidly generated scar tissue. Scarring is slight when the damaged outer layer of skin is healed by rebuilt tissue. When we damage the thick layer of tissue beneath the skin, rebuilding is more complicated. Our bodies lay down collagen fibers (a protein which is naturally produced by the body) and this usually results in a highly obvious scar. A permanent reminder of the injury is left behind. So, a dressing that can induce scarless healing is needed. Historically, a dressing was usually a piece of material, sometimes cloth, but the use of cobwebs, dung, leaves and honey has also been described. However, modern dressings include gauzes, semipermeable films, low adherent dressings, gels, foams, hydrocolloids, alginates, hydrogels and polysaccharide pastes. Wound dressings are passive, active or interactive. Passive dressings simply provide cover while active or interactive dressings are capable of modifying the physiology of the wound environment. Interactive dressings include hydrocolloids, hydrogels, alginates, foam dressings and antimicrobial dressings. [17, 20, 85] Traditionally dry wound dressings are considered to be good for healing wounds i.e. the wound should be covered with gauze or left open. But it has been observed by Winter [191] that when wound is left open to air without any dressing, a scab i.e. a dry covering covers the wound and decreases the rate of epithelialization. On the other hand, if moist dressing is used in place of dry dressings scab will not form and rate of healing increases as moist dressings provide low oxygen tension which helps in wound healing, these dressings not only keep cells viable which enables them to release growth factors while maintaining contact between them and the healing tissues, but may also modulate or stimulate their proliferation, these dressings decrease the pain at rest, during ambulation and during dressing changes also moist environment allows rapid and efficient delivery of any added antimicrobial agent thus prevent the wound from infection. So, the dressings that create and maintain a mois t environment, however, are now considered to provide the optimal conditions for wound healing. 2 Requirements of an ideal wound care system These characteristics should be present in the ideal wound care system (a) it should be capable of maintaining a high humidity at the wound site, (b) it should be non-toxic, (c) non-allergenic, (d) it can be removed without causing trauma to the wound, (e) it should pe impermeable to bacteria, (f) Thermally insulating, (g) it should be soft to touch, (h) it should allow proper gaseous exchange, (i) it should be free from particulate and toxic product, (j) promote tissue reconstruction processes and (k) it should be cost effective. [20, 165, 177] Out of all the dressings hydrocolloids, alginates and hydrogels each one has its own advantages and limitations but hydrogels are best and have all the characteristics that are needed in an ideal wound dressing. All the above mentioned characteristics can be achieved in hydrogel wound dressings. 3 Hydrogels for Wound Healing Applications Hydrogels are natural or synthetic cross-linked polymers used in a variety of medical and biomedical applications. Hydrogels consist of a matrix of insoluble polymers with up to 96% water content enabling them to donate water molecules to the wound surface and to maintain a moist environment at the wound bed. They are used in the construction of contact lenses, drug-delivery vehicles, wound dressings and as physiological electrodes or sensors. [17] Examples of hydrogel include Aquaform, Intrasite, GranuGel, Nu-Gel, Purilon, Sterigel. These also have the ability to absorb a degree of wound exudate. They transmit moisture vapour and oxygen, but their bacterial and fluid permeability is dependent on the type of secondary dressing used. [20] Hydrogels swell or shrink in aqueous solutions due to the association, dissociation and binding of various ions to polymer chains. These systems may swell in water until an equilibrium state is reached and retain their original shape. The interactions responsible for water sorption by hydrogels include the process of hydration, which is connected to the presence of such chemical groups as -OH, -COOH, -CONH2, -CONH-, and -SO3H and the existence of capillary areas and differences in osmotic pressure. The forces that make hydrogel dissolution impossible are presence of covalent bonds between individual polymer chains, hydrophobic and electrostatic interactions. [46] These are hydrophilic polymer networks which may absorb from 10-20% (an arbitrary lower limit) up to thousands of times their dry weight in water. These may be chemically stable or they may degrade and dissolve. They are called ‘reversible, or ‘physical gels when the networks are held together by molecular entanglements, and/or secondary forces including ionic, H-bonding or hydrophobic forces. [13, 14, 15] Hydrogels are called ‘permanent or ‘chemicalgels when they are covalently-crosslinked networks as shown in 1. Hydrogels can be made by irradiation, freeze-thawing or chemical methods. Out of all the methods, irradiation is considered as a suitable tool for the formation of hydrogels as in this method there is easy control of processing, no need of adding initiators or cross-linkers which are harmful, and have the possibility of formation and sterilization in one step. But as everything has its own advantages and disadvantages this method also has a disadvantage which is hydrogels formed by this method have poor mechanical strength. Nowadays, Freeze thawing technique is generally used to prepare hydrogels having good strength, stability and no crosslinkers and initiators. But the main disadvantage is that the prepared hydrogels have opaque appearance and limited swelling and thermal stability. [120] In comparison to the traditional gauze therapy the application of a hydrogel seems to significantly stimulate wound healing. [11] Various natural and synthetic polymers having good biocompatibility are used to develop hydrogel wound dressing. These polymers include natural polymers such as alginate, chitosan, gelatin and collagen and synthetic polymers such as polyurethane, poly(ethylene glycol), polycaprolactone, poly vinyl pyrrolidone, poly(lactide-co-glycolide), polyacrylonitrile , poly(amino acid), etc. Table 1 below shows different hydrophilic polymers used to synthesize hydrogel matrices. Table 1 Hydrophilic polymers used to synthesize hydrogel matrices. [13] Hydrogels may be classified as homopolymer hydrogels, copolymer hydrogels, multipolymer hydrogels, and interpenetrating polymeric hydrogels. Homopolymer hydrogels are crosslinked networks of one type of hydrophilic monomer unit, whereas copolymer hydrogels are produced by the crosslinking of two comonomer units, one of which must be hydrophilic. Multipolymer hydrogels are produced by the crosslinking of more than three monomers. Finally, interpenetrating polymeric hydrogels are produced by the swelling of a first network in a monomer and the reaction of the latter to form a second intermeshing network structure. [46, 47] Also, it has been shown that the blending of a natural polymer with a synthetic polymer seems to be a good method for obtaining materials having required mechanical and thermal properties in comparison to pure components. It is also a simple method by which suitable shapes such as films, sponges and hydrogels can be obtained easily to realize a variety of biomedical devices. 2 shows healing is faster with the hydrogel dressing than with the gauze dressing. Wound area covered by hydrogel decreases faster with increasing healing period. On the contrary, the wound covered by gauze dressing reduces by only half a percent even after 14 days. [192] 3.1 Natural Hydrogels Natural polymers, such as chitin, chitosan, alginate, collagen, elastin, genipin, gelatin, cellulose etc. have been used for dressing wounds because they play an important role in the healing process. [47] Chitosan is a partially deacetylated form of chitin. Chitin as BeschitinÃ’, Unitika, is also commercially available as dressing in Japan. [28] But as far as chitosan is concerned it is biocompatible, biodegradable, haemostatic, fungistatic [54] and non-toxic and can be successfully used as gels, films, fibres etc. This polymer also show antibacterial properties and possess good wound healing properties. [60, 61, 62] It has many applications as wound dressing, drug delivery device and as scaffold for tissue engineering. [63, 64] Some of the examples of wound dressings are given below which use chitosan as one of the biomaterial. Asymmetric chitosan membranes have been developed by using immersion-precipitation phase-inversion method. [123, 124, 125] These asymmetric chitosan membranes are homogeneous and have porous structure. This membrane was prepared by preheating casted chitosan solution in oven for different time periods for dry phase separation and then immersed in to coagulant tank for wet phase separation and were subsequently freeze-dried. The skin layer acts as the rate controlling barrier for the release of drug and the porous layer provide mechanical support to the skin layer. The water vapor transmission rate, gas permeability, PBS solution absorption, in-vitro degradation, cell culture, bacterial penetration and wound healing test of this dressing were carried out. These membranes are effective in controlling evaporative water loss, showed excellent oxygen permeability and also antibacterial in nature. These are also found to be an urgent hemostat. In another study, silver sulphadiazine was inc orporated as an antimicrobial agent to this asymmetric dressing. The release behaviour of both silver and sulphadiazine ions were studied and found to be significantly different from one another. Silver ions displayed a slow release behavior while sulphadiazine ions exhibited burst effect on first day of the drug release and then slowly tapered off. It is because of the interaction of silver with amino group of chitosan leading to its slow release throughout whereas, as the sulphadiazine ions were free to diffuse through the membrane to reach the wound site thus they showed a burst release. The membranes were further found effective against P. aerugniosa and S. aureus. In one of the papers, novel wound dressings were formed that composed of chitosan film and Minocycline Hydrochloride (MH) and commercial polyurethane film (Tegaderm) as a backing. It is also a useful formulation for the treatment of severe burn wounds. Water vapor and oxygen can permeate the Tegaderm film but water cannot. The tegaderm film support the polymer membrane. [126] In one of the studies, a silver nanocrystalline chitosan (SNC) wound dressing composed of nano-silver and chitosan was constructed by self-assembly and nanotechnology and used for treating deep partial-thickness wounds. In this, sterility and pyrogen testing were performed to ensure biosafety. These dressings promote wound healing and combat infection, and also decrease the risk of silver absorption in comparison with silver sulphadiazine (SSD) dressings. [127] There is also one more method of forming wound dressing composed of chitosan i.e. the formation of polyelectrolyte complex of gum kondagogu (GKG) and chitosan. This complex is formed by the electrostatic interaction between carboxyl group of gum and amine group of chitosan. This method is more advantageous as it avoids the use of organic solvents, chemical crosslinking agents and thus reduces the toxicity and undesirable side effects. In this, diclofenac sodium is used as model drug. The diclofenac loaded complex of gum kondagogu/ chitosan shows drug release which changes with change in pH. The drug release was higher at pH 6.8 as compared to pH 1.2, due to higher swelling of complex at higher pH. This holds a great potential as a natural polymer based delivery device for controlled delivery of drugs like diclofenac sodium for two reasons: (i) to reduce dosing frequency and (ii) lower the gastric toxicity. [152] Semi-interpenetrating polymer networks (SIPNs) composed of chitosan (CS) and poloxamer were prepared in order to improve the mechanical strength of CS. The WVTR was found to be 2508.2 ±65.7 gm−2 day−1, i.e. these can maintain a moist environment at wound site which enhance epithelial cell migration. Also, the in vitro assessment of SIPNs showed proper biodegradation and low cytotoxicity and in vivo is carried out on experimental full thickness wounds in a mouse model and found that the wounds covered with these were completely filled with new epithelium without any significant adverse reactions after 3 weeks. In one of the papers, a kind of surgical wound dressing, the chitosan-gelatin sponge wound dressing (CGSWD) having good antibacterial property is prepared. The in vitro test showed that the antibacterial effect of CGSWD on E. coli K88 is better than that of penicillin, and the effect on S. aureus is also better than that of cefradine. [137] One more wound dressing consists of two separate layers were prepared in which the upper layer is a swellable hydrogel material which can absorb exudates and also serve as mechanical and microbial barrier while lower layer is a chitosan acetate foam incorporated with the anti-microbial agent chlorherxidine gluconate. [183] The antimicrobial activity is checked by the Bauer-Kirby Disk Diffusion Test, inhibition zones can be clearly seen around the discs of chitosan acetate foams incorporated with chlorhexidine gluconate, in culture plates inoculated with either Gram-negative or positive bacteria showing that the dressing is antimicrobial in nature. Blending is a convenient and effective method to improve physical and mechanical properties of hydrogels. So modification of chitosan is done by blending with other polymers like cellulose. [178] In this, E. coli and S. aureus were used as the test bacteria to examine the antibacterial properties of chitosan, cellulose and chitosan/cellulose blends. The numbers of colony of these bacteria formed on the test membranes are shown in s 5 and 6. It was noted that the numbers of colony of all test bacteria formed on the chitosan/cellulose blend membranes were decreased with the increase of chitosan concentration. These blends are more effective against E. coli than that of S. aureus, as indicated by the lower colony unit. Thus these dressings are suitable to use as an antimicrobial wound dressing. Chitosan due to its structural properties has the ability to heal wounds without scar formation. [198] Since chitosan is composed of D-glucosamine, which is also the component present in the disaccharide subunits of hyaluronic acid, chitosan tries to structurally mimic hyaluronic acid and exerts similar effects. [197] It has been known that the fetal wound healing takes place without fibrosis or scar formation due to the presence of hyaluronic acid. [199] In one of the studies, Chitosan as a semi-permeable biological dressing maintains a moist environment and prevent the wound site from dehydration and contamination. In addition, digital colour separation analysis of donor site scars demonstrated an earlier return to normal skin colour at chitosan-treated areas as shown in 7. [196] Collagen is also a biopolymer that is used as a polymer for making wound dressing and drug delivery devices as it is biocompatible and biocompatibility of a material applied to wound tissue is a prerequisite for optimal wound environment and facilitation of the healing processes. A new collagen dressing with gentamycin or amikacin was prepared in one of the research work and these follow the basic requirement of antibacterial bandages. The dressing is composed of two collagen biomaterials—membrane and sponge—both possessing good tissue biocompatibility. These dressing released antibiotics slowly and show the antibacterial treatment in experimentally infected superficial wounds in mice. Thus, it can be used for the treatment of infected wounds in humans. [26] As discussed previously that both chitosan and collagen are excellent materials that can be used as wound dressing materials. So it has been seen that if both are used simultaneously then what will be the effect. It is found that the wound dressings composed of chitosan crosslinked collagen sponge (CCCS) enhance the diabetic wound healing. Collagen crosslinked with chitosan showed several advantages required for wound dressing, including the uniform and porous ultrastructure, less water imbibition, small interval porosity, and high resistance to collagenase digestion and slow release of FGF from CCCS/FGF. [138] Following moist healing concept, alginates which are able to absorb exudates from wound have become one of the most important materials for wound management. [52, 53, 54, 55, 56] In this particular field, the properties of alginate fibers are unparalleled in many respects. Alginate based products form a gel and effective in removing out of the wound on the contrary to traditional cotton and viscose fibres, which can entrap in the wound developing discomfort during dressing removal. [55] Also, the alginate fibres are non-toxic, non-carcinogenic, non-allergic, haemostatic, biocompatible, of reasonable strength, capable of being sterilized and easily processable. Sorbsanâ„ ¢ was first commercialized in 1981 and after that there were many dressings launched. The alginate fibers can be converted into wound dressings by using a number of textile processes. Because of its simplicity and also the high absorbency of the product, nonwoven is the main form of alginate wound dressings. [19] The antimicrobial action of alginate dressing can be seen as in 8 which shows the antimicrobial action of silver containing alginate fibers against E. Coli. There was 100% reduction in bacteria count within 5 hr after the fibers were placed in contact with solutions containing the bacteria. Sorbsan alginate fibers showed some antimicrobial activity while AquacelTM (made of carboxymethyl cellulose), does not show any antimicrobial effect. [18] Gelatin widely found in nature and is the major constituent of skin, bones, and connective tissue. Gelatin can easily be obtained by a controlled hydrolysis of the fibrous insoluble protein, collagen. [195] This is also used in number of biomedical applications like wound dressings. Hydrogel wound dressing from gelatin, oxidized alginate and borax were prepared and the composite matrix promotes wound healing because of alginate, has haemostatic effect of gelatin and is antiseptic because of borax. The water vapour transmission rate (WVTR) of the hydrogel was calculated and found to be 2686 ±124 g/m2/day indicating that this hydrogel can maintain a proper fluid balance at the wound site which helps in cell migration. 2 shows the loss of water vapour with time through the hydrogel when placed in a moisture rich environment. [119] Genipin has been used to crosslink chitosan membranes to control swelling ratio and mechanical properties. It increased its ultimate tensile strength but significantly reduced its strain-at-fracture and swelling ratio. It had significantly less cytotoxicity for human fibroblasts and slower degradation rate compared to the glutaraldehyde-crosslinked membrane. This genipin crosslinked chitosan membrane can be successfully used as a wound dressing. [132] Bacterial cellulose is a natural polymer consisting of microfibrils containing glucan chains bound together by hydrogen bonds. Bacterial cellulose with chitosan combines properties such as bioactivity, biocompatibility, and biodegradability of the two biopolymers and form an ideal material for dressing wounds. [66, 67] These are antibacterial and scar preventive in nature too. Since natural polymers have been considered limited in their applications for wound-dressing materials as their low mechanical properties and shortage of processing. So we move towards the synthetic polymers that can be used for wound healing applications. 3.2 Synthetic Hydrogels Synthetic polymers are also being used successfully in biomedical applications as one of the materials because of their wide range of mechanical properties, suitability for easily forming into a variety of different shapes, and low production costs. In an ideal dressing both the characteristics i.e. antimicrobial ability and moist healing environment should be present, so in order to prevent the wound from dehydration and bacterial penetration a new dressing composed of polyurethane is designed in such a way that the upper layer of the dressing is microporous (pore size Polyvinyl pyrrolidone (PVP) is one of the most widely used synthetic polymers in medicine because of its solubility in water and its extremely low cytotoxicity. Hydrogels prepared by radiation crosslinking of an aqueous solution of polyvinyl pyrrolidone (PVP) have been used as wound dressing. [21] These are biocompatible, reduces pain, easily replacable, permeable to oxygen, maintain moist environment at the wound site. Polyvinyl alcohol (PVA) is a well-known polymer because it is biocompatible and have required mechanical properties and polyethylene oxide (PEO) is a hydrophilic semicrystalline polyether which is biocompatible, non toxic, non polar, non antigenic and non immunogenic and is highly desirable in most biomedical applications requiring contact with physiological fluids. A hydrogel composed of PEO for wound dressing is prepared and PVA is added to give toughness to the hydrogel by electron beam irradiation and found that these hydrogels showed satisfactory properties for wound dressing that has been evaluated by creating wound on the back of the marmots. [157] The hydrogel gives a wet environment to wounds which causes faster healing compared with the gauze dressing with a dry environment. The weight of the hydrogel increases quickly at the earlier stages, up to 4 days, due to absorption of effusion produced from the wound as shown in Table 2. After that, the production of effusion from the wound ceases and the weight of the hydrogel decreases due to evaporation of the water in the hydrogel. This means that the healing of wound proceeds smoothly with time. The hydrogel can be peeled off easily from the wound at the time of removal. Table 2 Absorption of effusion from wound of dressing during healing. [157] The toughness of PEO hydrogel is improved by the addition of PVA and tensile strength is measured and found that as shown in 10 and 11, the tensile strength and elongation decrease with increasing dose because of the increase of crosslinking. Various synthetic polymers as discussed above are used for wound dressing applications. But the major problem with these materials is their biocompatibility characteristics are often unsatisfactory and their interaction with living tissues is a major problem. So a combination of both natural and synthetic polymers is the better option to make a hydrogel having biocompatibility and desired mechanical strength. 3.3 Blended hydrogels Since both the natural and synthetic polymers have their own advantages and disadvantages so a combination of natural and synthetic polymers can endow the optimal properties necessary for wound repair. [47] The combination of natural and synthetic polymers is used in the biomedical, bioengineering and biotechnology field nowadays because of their great potential. A blended hydrogel composed of polyvinyl alcohol/polyvinyl pyrrolidone and charcoal were prepared by single ‘‘freezing and thawing or two-step ‘‘freezing and thawing and ÃŽ ³-ray irradiation and applied as wound dressing. It is found that the absorption of S. aureus and P. aeruginosa by charcoal/PVA/PVP hydrogels was larger than those by PVA/PVP hydrogels, this is due to the absorption and attachment capability of bacteria by charcoal, this can be shown in 12 given below. [22] The most classical way of fabricating a CS based wound dressing has been to design an asymmetric composite structure. In this method, the Cotton fabric was coated with chitosan (CS) and polyethylene glycol (PEG) followed by freeze-drying. The outer dense layer helps in preventing the microbial passage across the dressing and provides a rate controlling barrier for water vapor permeation, while the inner porous layer provides a high surface area for the exudates absorption. For the absorption of wound exudates porosity is the prime requirement in a dressing. It has been found that these dressings have the porosity 54-70% and the pore size was in the range of 75-120 µm. [45] The increase in the PEG content in the blend composition led to an enhanced destabilization of pores, leading to an increase in the pore size with elongated morphology. There seems to be phase separation between the two components which is an important factor for the observed behavior of the porous structure. Cot ton fabric has been used as the support layer for the CS-PEG layer and leads to very thin and light weight structures. The structure of the dressing has been designed in such a way that it leads to the high porosity of the bulk structure. The thickness of CS coating plays an important role in the development of the porosity on the surface. The influence of the CS thickness on the surface morphology is presented in 13 given below. PEG addition to CS makes significant alteration in the surface morphology of this CS-PEG/cotton membrane (freeze-dried), henceforth known as CPC membrane. There is a distinct trend in the loss of inherent elongated porous structure in membranes and formation of the partially collapsed porosity takes place due to the PEG addition. This suggests that a very limited interaction between CS and PEG exists which is reflected in the observed surface morphology. It has been observed that higher the amount of PEG, the higher is the pore destabilization leading to larger pores. This is evident from the morphology of the CPC membrane at 50% PEG-20 content as shown in 14.45 On the above matrix, the addition of PVP and drug followed by coating on the cotton fabric and freeze drying of the coated matrix is also done. It has been found that the drug Hydrogels for Wound Healing Applications Hydrogels for Wound Healing Applications Abstract This chapter discusses about the hydrogels both natural and synthetic that can be used for wound healing applications. Also it discusses briefly about the various novel techniques that have been developed recently. Keywords: Hydrogels; Chitosan, Antimicrobial; Grafting; Blending; Wound dressing; Wound healing; Gene therapy, Stem cell therapy, Skin Engineering, pH and Thermosensitive polymers. 1 Introduction Healthcare is an essential aspect of human survival. So many biopolymers have generated interest in a number of biomedical applications. Wound management is one such area where management of cuts, ulcers, and sores needs dressings which help in promoting rapid wound healing in order to obtain both functional and cosmetic results. [45] There are different kinds of wound management products: staples or sutures, dressings or bandages, surgical sealants and adhesives, skin substitutes, and other biomaterials. [51] Human skin provides an effective barrier to microbial penetration and subsequent infection. However, once the wound has been developed in this barrier, the infection chances increases. In case of chronic wounds, the colonization and infection potential increases as the result of the presence of avascular eschar which provides an environment for the uninhibited growth of microorganisms. [89] The rate of infection is related to the type of wound, general wound care, and local health of the patient. [88, 90] For avoiding infection, good clinical practices are needed. The management of chronic wounds is a very costly practice and it also places an enormous drain on healthcare resources; studies have calculated the cost of wounds to the NHS to be about  £1bn a year. [166] So for lowering this cost such wound management products are needed that are more economical and effective. Out of all the above wound management products, here in this chapter we will discuss more about the wound dressings that will provide an optimal healing environment to the wound. A dressing is an adjunct used by a person for application to a wound in order to promote healing and/or prevent further harm. It is designed to be in direct contact with the wound, so it is different from the bandage in the manner that bandages are normally used to hold dressing in place. A wound is a break in the epithelial integrity of the skin and may be accompanied by disruption of the structure and function of underlying normal tissue. Wounds can be divided into four categories based on their appearance and stage of healing: Necrotic, sloughing, granulating and epithelializing wounds. [87] Wounds cause discomfort and are more prone to infection and other troublesome complications. [75] Some diseases like diabetes, ischaemia and conditions like malnourishment, ageing, local infection, local tissue damage due to burn leads to delay in wound healing. Infection is a major complication of burn injury and is responsible for 50-75% of hospital deaths. [76] Human skin has one of the greatest capacities to regenerate itself amongst all of the tissues in our body. It constantly replaces old cells with new cells, enabling it to repair itself when damaged. Wound healing is a complex-physiologic process, which consists of three overlapping phases: inflammatory, proliferative and remodeling phases. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors. During the inflammation process, neutrophils are the first leukocytes which come at the site of injury to rid it from bacterial contamination. Then, the monocytes and their conversion to macrophages initiate tissue repair by releasing a number of biologically active substances and growth factors that are necessary for the initi ation of tissue formation process. In the third process, fibroblasts proliferate and migrate into the wound space and started the deposition of the loose extracellular matrix. Endothelial cells grow into a wound simultaneously with fibroblasts and undergo angiogenesis. Finally, tissue remodeling takes place to reconstruct the basement membrane by the differentiation of keratinocytes as well as the formation of follicle cells. [43, 49, 50] A scar is an essential part of this natural healing process following any type of damage to the skin. This can occur after a surgical incision or the healing of a wound. As your body makes an effort to close an open wound and protect itself from infection, it replaces injured skin tissue with rapidly generated scar tissue. Scarring is slight when the damaged outer layer of skin is healed by rebuilt tissue. When we damage the thick layer of tissue beneath the skin, rebuilding is more complicated. Our bodies lay down collagen fibers (a protein which is naturally produced by the body) and this usually results in a highly obvious scar. A permanent reminder of the injury is left behind. So, a dressing that can induce scarless healing is needed. Historically, a dressing was usually a piece of material, sometimes cloth, but the use of cobwebs, dung, leaves and honey has also been described. However, modern dressings include gauzes, semipermeable films, low adherent dressings, gels, foams, hydrocolloids, alginates, hydrogels and polysaccharide pastes. Wound dressings are passive, active or interactive. Passive dressings simply provide cover while active or interactive dressings are capable of modifying the physiology of the wound environment. Interactive dressings include hydrocolloids, hydrogels, alginates, foam dressings and antimicrobial dressings. [17, 20, 85] Traditionally dry wound dressings are considered to be good for healing wounds i.e. the wound should be covered with gauze or left open. But it has been observed by Winter [191] that when wound is left open to air without any dressing, a scab i.e. a dry covering covers the wound and decreases the rate of epithelialization. On the other hand, if moist dressing is used in place of dry dressings scab will not form and rate of healing increases as moist dressings provide low oxygen tension which helps in wound healing, these dressings not only keep cells viable which enables them to release growth factors while maintaining contact between them and the healing tissues, but may also modulate or stimulate their proliferation, these dressings decrease the pain at rest, during ambulation and during dressing changes also moist environment allows rapid and efficient delivery of any added antimicrobial agent thus prevent the wound from infection. So, the dressings that create and maintain a mois t environment, however, are now considered to provide the optimal conditions for wound healing. 2 Requirements of an ideal wound care system These characteristics should be present in the ideal wound care system (a) it should be capable of maintaining a high humidity at the wound site, (b) it should be non-toxic, (c) non-allergenic, (d) it can be removed without causing trauma to the wound, (e) it should pe impermeable to bacteria, (f) Thermally insulating, (g) it should be soft to touch, (h) it should allow proper gaseous exchange, (i) it should be free from particulate and toxic product, (j) promote tissue reconstruction processes and (k) it should be cost effective. [20, 165, 177] Out of all the dressings hydrocolloids, alginates and hydrogels each one has its own advantages and limitations but hydrogels are best and have all the characteristics that are needed in an ideal wound dressing. All the above mentioned characteristics can be achieved in hydrogel wound dressings. 3 Hydrogels for Wound Healing Applications Hydrogels are natural or synthetic cross-linked polymers used in a variety of medical and biomedical applications. Hydrogels consist of a matrix of insoluble polymers with up to 96% water content enabling them to donate water molecules to the wound surface and to maintain a moist environment at the wound bed. They are used in the construction of contact lenses, drug-delivery vehicles, wound dressings and as physiological electrodes or sensors. [17] Examples of hydrogel include Aquaform, Intrasite, GranuGel, Nu-Gel, Purilon, Sterigel. These also have the ability to absorb a degree of wound exudate. They transmit moisture vapour and oxygen, but their bacterial and fluid permeability is dependent on the type of secondary dressing used. [20] Hydrogels swell or shrink in aqueous solutions due to the association, dissociation and binding of various ions to polymer chains. These systems may swell in water until an equilibrium state is reached and retain their original shape. The interactions responsible for water sorption by hydrogels include the process of hydration, which is connected to the presence of such chemical groups as -OH, -COOH, -CONH2, -CONH-, and -SO3H and the existence of capillary areas and differences in osmotic pressure. The forces that make hydrogel dissolution impossible are presence of covalent bonds between individual polymer chains, hydrophobic and electrostatic interactions. [46] These are hydrophilic polymer networks which may absorb from 10-20% (an arbitrary lower limit) up to thousands of times their dry weight in water. These may be chemically stable or they may degrade and dissolve. They are called ‘reversible, or ‘physical gels when the networks are held together by molecular entanglements, and/or secondary forces including ionic, H-bonding or hydrophobic forces. [13, 14, 15] Hydrogels are called ‘permanent or ‘chemicalgels when they are covalently-crosslinked networks as shown in 1. Hydrogels can be made by irradiation, freeze-thawing or chemical methods. Out of all the methods, irradiation is considered as a suitable tool for the formation of hydrogels as in this method there is easy control of processing, no need of adding initiators or cross-linkers which are harmful, and have the possibility of formation and sterilization in one step. But as everything has its own advantages and disadvantages this method also has a disadvantage which is hydrogels formed by this method have poor mechanical strength. Nowadays, Freeze thawing technique is generally used to prepare hydrogels having good strength, stability and no crosslinkers and initiators. But the main disadvantage is that the prepared hydrogels have opaque appearance and limited swelling and thermal stability. [120] In comparison to the traditional gauze therapy the application of a hydrogel seems to significantly stimulate wound healing. [11] Various natural and synthetic polymers having good biocompatibility are used to develop hydrogel wound dressing. These polymers include natural polymers such as alginate, chitosan, gelatin and collagen and synthetic polymers such as polyurethane, poly(ethylene glycol), polycaprolactone, poly vinyl pyrrolidone, poly(lactide-co-glycolide), polyacrylonitrile , poly(amino acid), etc. Table 1 below shows different hydrophilic polymers used to synthesize hydrogel matrices. Table 1 Hydrophilic polymers used to synthesize hydrogel matrices. [13] Hydrogels may be classified as homopolymer hydrogels, copolymer hydrogels, multipolymer hydrogels, and interpenetrating polymeric hydrogels. Homopolymer hydrogels are crosslinked networks of one type of hydrophilic monomer unit, whereas copolymer hydrogels are produced by the crosslinking of two comonomer units, one of which must be hydrophilic. Multipolymer hydrogels are produced by the crosslinking of more than three monomers. Finally, interpenetrating polymeric hydrogels are produced by the swelling of a first network in a monomer and the reaction of the latter to form a second intermeshing network structure. [46, 47] Also, it has been shown that the blending of a natural polymer with a synthetic polymer seems to be a good method for obtaining materials having required mechanical and thermal properties in comparison to pure components. It is also a simple method by which suitable shapes such as films, sponges and hydrogels can be obtained easily to realize a variety of biomedical devices. 2 shows healing is faster with the hydrogel dressing than with the gauze dressing. Wound area covered by hydrogel decreases faster with increasing healing period. On the contrary, the wound covered by gauze dressing reduces by only half a percent even after 14 days. [192] 3.1 Natural Hydrogels Natural polymers, such as chitin, chitosan, alginate, collagen, elastin, genipin, gelatin, cellulose etc. have been used for dressing wounds because they play an important role in the healing process. [47] Chitosan is a partially deacetylated form of chitin. Chitin as BeschitinÃ’, Unitika, is also commercially available as dressing in Japan. [28] But as far as chitosan is concerned it is biocompatible, biodegradable, haemostatic, fungistatic [54] and non-toxic and can be successfully used as gels, films, fibres etc. This polymer also show antibacterial properties and possess good wound healing properties. [60, 61, 62] It has many applications as wound dressing, drug delivery device and as scaffold for tissue engineering. [63, 64] Some of the examples of wound dressings are given below which use chitosan as one of the biomaterial. Asymmetric chitosan membranes have been developed by using immersion-precipitation phase-inversion method. [123, 124, 125] These asymmetric chitosan membranes are homogeneous and have porous structure. This membrane was prepared by preheating casted chitosan solution in oven for different time periods for dry phase separation and then immersed in to coagulant tank for wet phase separation and were subsequently freeze-dried. The skin layer acts as the rate controlling barrier for the release of drug and the porous layer provide mechanical support to the skin layer. The water vapor transmission rate, gas permeability, PBS solution absorption, in-vitro degradation, cell culture, bacterial penetration and wound healing test of this dressing were carried out. These membranes are effective in controlling evaporative water loss, showed excellent oxygen permeability and also antibacterial in nature. These are also found to be an urgent hemostat. In another study, silver sulphadiazine was inc orporated as an antimicrobial agent to this asymmetric dressing. The release behaviour of both silver and sulphadiazine ions were studied and found to be significantly different from one another. Silver ions displayed a slow release behavior while sulphadiazine ions exhibited burst effect on first day of the drug release and then slowly tapered off. It is because of the interaction of silver with amino group of chitosan leading to its slow release throughout whereas, as the sulphadiazine ions were free to diffuse through the membrane to reach the wound site thus they showed a burst release. The membranes were further found effective against P. aerugniosa and S. aureus. In one of the papers, novel wound dressings were formed that composed of chitosan film and Minocycline Hydrochloride (MH) and commercial polyurethane film (Tegaderm) as a backing. It is also a useful formulation for the treatment of severe burn wounds. Water vapor and oxygen can permeate the Tegaderm film but water cannot. The tegaderm film support the polymer membrane. [126] In one of the studies, a silver nanocrystalline chitosan (SNC) wound dressing composed of nano-silver and chitosan was constructed by self-assembly and nanotechnology and used for treating deep partial-thickness wounds. In this, sterility and pyrogen testing were performed to ensure biosafety. These dressings promote wound healing and combat infection, and also decrease the risk of silver absorption in comparison with silver sulphadiazine (SSD) dressings. [127] There is also one more method of forming wound dressing composed of chitosan i.e. the formation of polyelectrolyte complex of gum kondagogu (GKG) and chitosan. This complex is formed by the electrostatic interaction between carboxyl group of gum and amine group of chitosan. This method is more advantageous as it avoids the use of organic solvents, chemical crosslinking agents and thus reduces the toxicity and undesirable side effects. In this, diclofenac sodium is used as model drug. The diclofenac loaded complex of gum kondagogu/ chitosan shows drug release which changes with change in pH. The drug release was higher at pH 6.8 as compared to pH 1.2, due to higher swelling of complex at higher pH. This holds a great potential as a natural polymer based delivery device for controlled delivery of drugs like diclofenac sodium for two reasons: (i) to reduce dosing frequency and (ii) lower the gastric toxicity. [152] Semi-interpenetrating polymer networks (SIPNs) composed of chitosan (CS) and poloxamer were prepared in order to improve the mechanical strength of CS. The WVTR was found to be 2508.2 ±65.7 gm−2 day−1, i.e. these can maintain a moist environment at wound site which enhance epithelial cell migration. Also, the in vitro assessment of SIPNs showed proper biodegradation and low cytotoxicity and in vivo is carried out on experimental full thickness wounds in a mouse model and found that the wounds covered with these were completely filled with new epithelium without any significant adverse reactions after 3 weeks. In one of the papers, a kind of surgical wound dressing, the chitosan-gelatin sponge wound dressing (CGSWD) having good antibacterial property is prepared. The in vitro test showed that the antibacterial effect of CGSWD on E. coli K88 is better than that of penicillin, and the effect on S. aureus is also better than that of cefradine. [137] One more wound dressing consists of two separate layers were prepared in which the upper layer is a swellable hydrogel material which can absorb exudates and also serve as mechanical and microbial barrier while lower layer is a chitosan acetate foam incorporated with the anti-microbial agent chlorherxidine gluconate. [183] The antimicrobial activity is checked by the Bauer-Kirby Disk Diffusion Test, inhibition zones can be clearly seen around the discs of chitosan acetate foams incorporated with chlorhexidine gluconate, in culture plates inoculated with either Gram-negative or positive bacteria showing that the dressing is antimicrobial in nature. Blending is a convenient and effective method to improve physical and mechanical properties of hydrogels. So modification of chitosan is done by blending with other polymers like cellulose. [178] In this, E. coli and S. aureus were used as the test bacteria to examine the antibacterial properties of chitosan, cellulose and chitosan/cellulose blends. The numbers of colony of these bacteria formed on the test membranes are shown in s 5 and 6. It was noted that the numbers of colony of all test bacteria formed on the chitosan/cellulose blend membranes were decreased with the increase of chitosan concentration. These blends are more effective against E. coli than that of S. aureus, as indicated by the lower colony unit. Thus these dressings are suitable to use as an antimicrobial wound dressing. Chitosan due to its structural properties has the ability to heal wounds without scar formation. [198] Since chitosan is composed of D-glucosamine, which is also the component present in the disaccharide subunits of hyaluronic acid, chitosan tries to structurally mimic hyaluronic acid and exerts similar effects. [197] It has been known that the fetal wound healing takes place without fibrosis or scar formation due to the presence of hyaluronic acid. [199] In one of the studies, Chitosan as a semi-permeable biological dressing maintains a moist environment and prevent the wound site from dehydration and contamination. In addition, digital colour separation analysis of donor site scars demonstrated an earlier return to normal skin colour at chitosan-treated areas as shown in 7. [196] Collagen is also a biopolymer that is used as a polymer for making wound dressing and drug delivery devices as it is biocompatible and biocompatibility of a material applied to wound tissue is a prerequisite for optimal wound environment and facilitation of the healing processes. A new collagen dressing with gentamycin or amikacin was prepared in one of the research work and these follow the basic requirement of antibacterial bandages. The dressing is composed of two collagen biomaterials—membrane and sponge—both possessing good tissue biocompatibility. These dressing released antibiotics slowly and show the antibacterial treatment in experimentally infected superficial wounds in mice. Thus, it can be used for the treatment of infected wounds in humans. [26] As discussed previously that both chitosan and collagen are excellent materials that can be used as wound dressing materials. So it has been seen that if both are used simultaneously then what will be the effect. It is found that the wound dressings composed of chitosan crosslinked collagen sponge (CCCS) enhance the diabetic wound healing. Collagen crosslinked with chitosan showed several advantages required for wound dressing, including the uniform and porous ultrastructure, less water imbibition, small interval porosity, and high resistance to collagenase digestion and slow release of FGF from CCCS/FGF. [138] Following moist healing concept, alginates which are able to absorb exudates from wound have become one of the most important materials for wound management. [52, 53, 54, 55, 56] In this particular field, the properties of alginate fibers are unparalleled in many respects. Alginate based products form a gel and effective in removing out of the wound on the contrary to traditional cotton and viscose fibres, which can entrap in the wound developing discomfort during dressing removal. [55] Also, the alginate fibres are non-toxic, non-carcinogenic, non-allergic, haemostatic, biocompatible, of reasonable strength, capable of being sterilized and easily processable. Sorbsanâ„ ¢ was first commercialized in 1981 and after that there were many dressings launched. The alginate fibers can be converted into wound dressings by using a number of textile processes. Because of its simplicity and also the high absorbency of the product, nonwoven is the main form of alginate wound dressings. [19] The antimicrobial action of alginate dressing can be seen as in 8 which shows the antimicrobial action of silver containing alginate fibers against E. Coli. There was 100% reduction in bacteria count within 5 hr after the fibers were placed in contact with solutions containing the bacteria. Sorbsan alginate fibers showed some antimicrobial activity while AquacelTM (made of carboxymethyl cellulose), does not show any antimicrobial effect. [18] Gelatin widely found in nature and is the major constituent of skin, bones, and connective tissue. Gelatin can easily be obtained by a controlled hydrolysis of the fibrous insoluble protein, collagen. [195] This is also used in number of biomedical applications like wound dressings. Hydrogel wound dressing from gelatin, oxidized alginate and borax were prepared and the composite matrix promotes wound healing because of alginate, has haemostatic effect of gelatin and is antiseptic because of borax. The water vapour transmission rate (WVTR) of the hydrogel was calculated and found to be 2686 ±124 g/m2/day indicating that this hydrogel can maintain a proper fluid balance at the wound site which helps in cell migration. 2 shows the loss of water vapour with time through the hydrogel when placed in a moisture rich environment. [119] Genipin has been used to crosslink chitosan membranes to control swelling ratio and mechanical properties. It increased its ultimate tensile strength but significantly reduced its strain-at-fracture and swelling ratio. It had significantly less cytotoxicity for human fibroblasts and slower degradation rate compared to the glutaraldehyde-crosslinked membrane. This genipin crosslinked chitosan membrane can be successfully used as a wound dressing. [132] Bacterial cellulose is a natural polymer consisting of microfibrils containing glucan chains bound together by hydrogen bonds. Bacterial cellulose with chitosan combines properties such as bioactivity, biocompatibility, and biodegradability of the two biopolymers and form an ideal material for dressing wounds. [66, 67] These are antibacterial and scar preventive in nature too. Since natural polymers have been considered limited in their applications for wound-dressing materials as their low mechanical properties and shortage of processing. So we move towards the synthetic polymers that can be used for wound healing applications. 3.2 Synthetic Hydrogels Synthetic polymers are also being used successfully in biomedical applications as one of the materials because of their wide range of mechanical properties, suitability for easily forming into a variety of different shapes, and low production costs. In an ideal dressing both the characteristics i.e. antimicrobial ability and moist healing environment should be present, so in order to prevent the wound from dehydration and bacterial penetration a new dressing composed of polyurethane is designed in such a way that the upper layer of the dressing is microporous (pore size Polyvinyl pyrrolidone (PVP) is one of the most widely used synthetic polymers in medicine because of its solubility in water and its extremely low cytotoxicity. Hydrogels prepared by radiation crosslinking of an aqueous solution of polyvinyl pyrrolidone (PVP) have been used as wound dressing. [21] These are biocompatible, reduces pain, easily replacable, permeable to oxygen, maintain moist environment at the wound site. Polyvinyl alcohol (PVA) is a well-known polymer because it is biocompatible and have required mechanical properties and polyethylene oxide (PEO) is a hydrophilic semicrystalline polyether which is biocompatible, non toxic, non polar, non antigenic and non immunogenic and is highly desirable in most biomedical applications requiring contact with physiological fluids. A hydrogel composed of PEO for wound dressing is prepared and PVA is added to give toughness to the hydrogel by electron beam irradiation and found that these hydrogels showed satisfactory properties for wound dressing that has been evaluated by creating wound on the back of the marmots. [157] The hydrogel gives a wet environment to wounds which causes faster healing compared with the gauze dressing with a dry environment. The weight of the hydrogel increases quickly at the earlier stages, up to 4 days, due to absorption of effusion produced from the wound as shown in Table 2. After that, the production of effusion from the wound ceases and the weight of the hydrogel decreases due to evaporation of the water in the hydrogel. This means that the healing of wound proceeds smoothly with time. The hydrogel can be peeled off easily from the wound at the time of removal. Table 2 Absorption of effusion from wound of dressing during healing. [157] The toughness of PEO hydrogel is improved by the addition of PVA and tensile strength is measured and found that as shown in 10 and 11, the tensile strength and elongation decrease with increasing dose because of the increase of crosslinking. Various synthetic polymers as discussed above are used for wound dressing applications. But the major problem with these materials is their biocompatibility characteristics are often unsatisfactory and their interaction with living tissues is a major problem. So a combination of both natural and synthetic polymers is the better option to make a hydrogel having biocompatibility and desired mechanical strength. 3.3 Blended hydrogels Since both the natural and synthetic polymers have their own advantages and disadvantages so a combination of natural and synthetic polymers can endow the optimal properties necessary for wound repair. [47] The combination of natural and synthetic polymers is used in the biomedical, bioengineering and biotechnology field nowadays because of their great potential. A blended hydrogel composed of polyvinyl alcohol/polyvinyl pyrrolidone and charcoal were prepared by single ‘‘freezing and thawing or two-step ‘‘freezing and thawing and ÃŽ ³-ray irradiation and applied as wound dressing. It is found that the absorption of S. aureus and P. aeruginosa by charcoal/PVA/PVP hydrogels was larger than those by PVA/PVP hydrogels, this is due to the absorption and attachment capability of bacteria by charcoal, this can be shown in 12 given below. [22] The most classical way of fabricating a CS based wound dressing has been to design an asymmetric composite structure. In this method, the Cotton fabric was coated with chitosan (CS) and polyethylene glycol (PEG) followed by freeze-drying. The outer dense layer helps in preventing the microbial passage across the dressing and provides a rate controlling barrier for water vapor permeation, while the inner porous layer provides a high surface area for the exudates absorption. For the absorption of wound exudates porosity is the prime requirement in a dressing. It has been found that these dressings have the porosity 54-70% and the pore size was in the range of 75-120 µm. [45] The increase in the PEG content in the blend composition led to an enhanced destabilization of pores, leading to an increase in the pore size with elongated morphology. There seems to be phase separation between the two components which is an important factor for the observed behavior of the porous structure. Cot ton fabric has been used as the support layer for the CS-PEG layer and leads to very thin and light weight structures. The structure of the dressing has been designed in such a way that it leads to the high porosity of the bulk structure. The thickness of CS coating plays an important role in the development of the porosity on the surface. The influence of the CS thickness on the surface morphology is presented in 13 given below. PEG addition to CS makes significant alteration in the surface morphology of this CS-PEG/cotton membrane (freeze-dried), henceforth known as CPC membrane. There is a distinct trend in the loss of inherent elongated porous structure in membranes and formation of the partially collapsed porosity takes place due to the PEG addition. This suggests that a very limited interaction between CS and PEG exists which is reflected in the observed surface morphology. It has been observed that higher the amount of PEG, the higher is the pore destabilization leading to larger pores. This is evident from the morphology of the CPC membrane at 50% PEG-20 content as shown in 14.45 On the above matrix, the addition of PVP and drug followed by coating on the cotton fabric and freeze drying of the coated matrix is also done. It has been found that the drug