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July 16, 2004, a devastating fire engulfed a private school in Kumbakonam ,Tamilnadu. Over 90 children lost their lives and scores suffered burn injury. Doctors in hospitals turned to collagen membrane, developed by the Central Leather Research Institute to treat the injured children, showing thereby the long distance traversed by this premier Institute diversifying its areas of research from leather to skin.
The skin is often known as "the largest organ in the human body". It plays several important functions including thermo-regulation and protection of internal organs from vagaries of external environment. It derives its unique and special properties from its architectural beauty and structural integrity while maintaining the barrier between internal organs and external environment.
Structural biology and applications of skin have remained an important research area in Central Leather Research Institute (CLRI) since its inception. During the 1950’s, the structure of the main protein contained in skin, namely collagen, was an area of intense research. Prof. G.N. Ramachandran and his group in the University of Madras chose to work out the structure of collagen. CLRI provided him with the requisite sample of collagen in the pure form. The structure of collagen, which later came to be known as Madras Triple Helical Structure, was mentioned on August 7, 1954, a few months after the report of double helix structure of DNA by G.N. Ramachandran.
CLRI, in the early years of collagen research during 1960s and 70’s, made important contributions in recognizing new cross-links and in understanding of nutrition induced disorders of the connective tissues. Structural changes in collagen under conditions of arthritis and myocardial infarction were reported. New experimental techniques in unraveling the matrix structure of skin and collagenous tissues were developed. With this CLRI emerged as an important centre in fundamental research in collagen.
Skin is susceptible to different types of trauma or external injury on the one hand and to many genetic and mal-nutrition induced disorders on the other. Wound in skin alters the normal architecture of the skin and its function. In some cases abnormal scars are formed. Restoration to the normal architecture and function is promoted by healing. Wound healing requires regeneration of the lost tissue. Hastening of healing of wound calls for clever manipulation of cell biology of the skin. Healing of wounds in human skin after the incidence of trauma by burns or other types of injury has attracted the attention of CLRI.
Keloid, a skin disorder resulting from over growth of the tissue, affects generally women with coloured skins. Hypertrophic scars and keloids influence the physical and mental states of the affected person. Molecular mechanism in scar formation has been probed with a view to promote a suitable therapeutic intervention. A therapeutic insight in the management of keloid has been established in collaboration with the plastic surgeons.
Wound healing involves different phases namely inflammation, proliferation, remodeling and re-epithelialization. A balanced equilibrium of these processes is essential for successful wound healing. Modulators of the various phases of wound healing have been identified and applied successfully in promoting wound healing on human subjects.
The efficacy of frog skin in wound healing in human skin has already been demonstrated. A phospholipid contained in frog skin is a potent anti-inflammatory agent while the protein fractions from frog skins exhibit anti-microbial action against pathogenic and non-pathogenic bacteria.
Traditional wisdom advises the use of several natural products in health care. The efficacy of botanicals in skincare and wound healing have been investigated with success. Healing efficacy of crude alcoholic extract from dry leaves of Datura alba on burn wounds has been shown to be comparable to silver sulfadiazine (currently used drug), in dose dependent pattern. An isolated compound from Sida acuta has been shown to aid significantly in managing angiogenesis. Curcumin reduces hydroxyproline levels associated upon bleomycin administration, without respiratory distress. Similarly, Curcumin leads to a significant decrease in total lung protein content and many other parameters. It aids in amelioration of bleomycin induced inflammatory and fibrotic changes.
Also a process for reconstituting and for preparing collagen substratum with potential applications in grafting in management of burn wounds in human beings has been standardized. The process is simple and ensures the separation of Type IV collagen. The product is stable and is devoid of biotoxicity.
Anti bacterial drugs loaded microspheres have been impregnated onto purified collagen from calfskins and the resulting products are incorporated into fibrillar systems. The developed novel collagen scaffold impregnated with antibacterial agent delivers the drug in a controlled manner.
A plant based-reconstituted collagen substratum with applications in wound healing has been developed. The product exhibits potential medical application as a biological cover for non-healing ulcers as well as burn injuries.
CLRI has now transferred its technologies for manufacturing collagen sheets not only to domestic companies, it is also poised to provide the know-how to manufacture a whole range of wound management products e.g. reconstituted chemically modified collagen sponge, reconstituted collagen plast and haemostat, fibrogel, aminograft and collagen particle to foreign companies.
*Director, PIB, New Delhi
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