Artificial skin, dressing materials and novel drug delivery systems Part 1

Introduction
Skin wounds due to burns must surely be the most painful condition known to both humans and animals. A significant percentage of both medical and veterinary emergency hospital admissions each year are due to burns. The most dangerous complication of a burn is the exposure of the skin to the underlying tissues and the consequent risk of bacterial infections and death due to septicaemia.

Therefore, to provide a suitable cover for the burnt portion of the skin and get the burn to start healing is an immediate priority in the treatment of burns. Skin substitutes and dressings for burns have varied from Aloe vera gel, potato peels to sponge and artificial skin. The current article explores some facets of the emerging new trend in searching for effective skin cover like artificial skin.

History
Probably the desire to make new skin is as old as the time of the cave human who accidentally injured himself in a hunting expedition. However, since that latent wish, quite a few millennia have passed from idle contemplation of the wish to it's transformation in to a reality.

It was only two centuries ago that Louis Menard, a French chemist invented a polymer called collodion from a solution of cellulose nitrate in alcohol and ether. This solution was found to dry up and form a film when poured over wounds. Gradually the compound gained popularity as a dressing for wounds. The collodion once poured over the wound dried and formed a peelable film that could be comfortably peeled off after the wound healed. Such then was the fledgling start of field that is rapidly expanding.

Polymer scaffolds
Frames for skin growth As early as 1986 Langer and Vacanti were able to successfully grow liver cells on a polymer matrix which functioned effectively after being transplanted into animals. Langer found that polymers like ethylene-vinyl acetate, which take up very little water, could release compounds in a sustained manner.

When such dressing material were applied on wounds,they were found to have a very beneficial role in protecting against deadly infection and fluid loss. Besides, the polymers accelerated wound healing by promoting the release of chemical growth factors and signals that stimulate normal cellular growth at the wound site.

Polymers with adjustable pore size
In the recent past, research has focussed on the novel properties of a polymer membrane with an adjustable pore size. The synthetic biodegradable matrix called Polyactive, which is an elastomeric poly (ether)/ poly (ester) block copolymer has been found to be quite useful in dermal regeneration.

This matrix is available as a porous substrate, with gradually changing pore size (BISKIN-M), or as a bilayer made of a porous underlayer with a fully dense surface layer (BISKIN). Van Dorp et al at the department of biomaterial research, Leiden University Medical Centre, The Netherlands have studied the efficacy of this novel block copolymer in promoting dermal regeneration.

Other applications
It is not only as a matrix for skin cells to grow that polymer scaffolds are beginning to gain application but in a very wide and diverse spectrum of cell and tissue repair. Polymer scaffolds represent an emerging and interesting new area of research.

Their application in a wide area of research extends from using them as matrices for growing nerve cells for use in spinal cord repairs, to bone or cartilage cells for joint repairs, pancreatic cells to make insulin for diabetics, and liver cells to make livers for transplantation. Polymers have been found to make an excellent scaffold for growing cells. Today, more than 25 different cell types of both human and animal origin can be grown on the polymer scaffolds.

Fungal membranes as skin substitutes
Hung et al at the Graduate Institute of Cell and Molecular Biology have been studying the cytotoxicity and immunogenicity of Sacchachitin, a membrane derived from the fruiting body of a fungus called Ganoderma tsugae. The weavable skin substitute has been shown to promote skin wound healing. This, in turn, is expected to promote angiogenesis, granulation, and faster new tissue formation, leading to faster wound healing.

In another interesting study, Su et al at the Centre for Biotechnical Development and Research, Taipei Medical College, have examined the role of the Sacchachitin membrane, prepared from Ganoderma tsugae for its effects on wound healing and the proliferation and migration of fibroblast cells. Their results indicated that both 0.01% w/v of Sacchachitin and chitin significantly enhanced the proliferation and migration of fibroblast cells.

Artificial skin
Research on artificial tissues has progressed significantly. In 1997, artificial skin was found to heal ulcers in diabetics. Listed below are some types of artificial skin that are becoming popular and also some interesting observations with the use of artificial skin and other derivatives.

Apligraf
Apligraf is a bilayered product composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I bovine collagen. Genevrier Laboratories in France have developed a cell-based product that is similar to an epidermis sheet of cultured autologous keratinocytes.

Yang et al at the department of chemical engineering, Dongguk University, Seoul, Korea have developed an artificial skin made of a stratified layer of keratinocytes and a dermal matrix with type I collagen containing fibroblasts.

Integra
Another artificial skin tissue that is gaining in popularity is known as Integra artificial skin. The tissue is essentially a dermal template made of bovine collagen, chondroitin-6-sulphate and a silastic membrane. It has been found to be effective in the clinical treatment of third degree burn wounds and full thickness skin defects due to different causes.

In the first step of tissue repair, a self neodermis is created and in the second step, a self epidermis is created over the neodermis. However, there have been varied opionions on the practical use of this artificial tissue. Some practitioners feel that it may be better to cover major burn wounds early in a single step by a skin substitute made of a dermal equivalent seeded in vitro with autologous keratinocytes ('composite-skin') from which a full thickness skin develops in vivo.

Alteration of adhesive properties
Myles et al at the department of chemical engineering, University of Florida have carried out an interesting experiment. They have modified the adhesive properties of collagen by covalent grafting with RGD peptides. By altering the adhesive properties of collagen, a controlled localization or redistribution of cells may be created. To modify the adhesive properties of collagen, the investigators have developed a method which involves covalent grafting with RGD peptides.

Shorter culturing periods
Kim et al at the department of plastic surgery, Kyoto University have developd an artificial skin substitute made up of two collagen sponge layers with different pore sizes and cross-link densities. A shorter culturing period is a definite advantage that this skin substitute has over others. Therefore, it presents a promising solution for urgent skin grafting that may be needed in animals or humans with severe generalised burns.

Gelatin containing artificial skin
Choi et al at the department of industrial chemistry, college of engineering, Hanyang University, Seoul, South Korea have developed a new sponge type of biomaterial to be used for either wound dressing or scaffold for tissue engineering. In their study, they were able to prepare an insoluble matrix made of gelatin and sodium hyaluronate (HA) by dipping the soluble sponge into 90% (w/v) acetone/water mixture containing a small amount of cross-linking agent, 1-ethyl-3-3-dimethylaminoproplycarbodiimide hydrochloride, EDC.

Artificial skin can help accelerate tendon repair
At the department of Surgery in Changsha, China, Hunan et al have found that artificial biological skin helps to prevent tendon adhesion after tendon repair.

Artificial skin as an invitro system for toxicity testing
According to Yang et al at the Laboratory of Tissue Engineering, Department of Chemical Engineering, Dongguk University, Seoul, Korea, artificial skin may also serve as useful alternative methods for in vitro tests to minimize the use of animals in ocular and dermal irritation testing. They have started preliminary trials to understand and assess the reaction of artificial skin to known chemical irritants like toluene, glutaraldehyde and sodium lauryl sulfate (SLS), and a nonirritant, such as polyethylene glycol.

References