MATISS · Biomaterials for wound healing and tissue regeneration

Final Activity Report Summary - MATISS (Biomaterials for Wound Healing and Tissue Regeneration)

Surface wounds, ranging from major burn injuries to poorly healing ulcers, are still a major cause of morbidity, and indeed mortality, throughout the world. While considerable advances in treatment have been achieved in the last decade, there still exists a need for more effective interventions. Previously, large areas of skin damage, such as large-area burns affecting the full thickness of the skin, would almost invariably prove fatal. Now so-called tissue regeneration matrices are used in attempts to close such wounds, exclude microbial infection, and provide a template into which new tissue may grow to regenerate the lost skin. Such matrices are usually made of a gel created from the structural protein, collagen. Current matrices, although life-saving in many instances, are very expensive, and often leave quite severe scarring and contractions, which have to be corrected with repeat surgery. Similarly, non-healing ulcers are a major problem in the elderly, especially diabetes sufferers, being present in some 1-3% of that population. A wide range of dressings are available, ranging from hydrogels to simple non-adherent dressings, but the major treatment is still compression dressing, and the problem still persists. This project set out to explore the potential of a novel type of gel, the cryogel, as a basis for skin regeneration matrices, and wound dressings. Ordinary hydrogels usually consist of a polymer network which attracts and immobilises water molecules, thus giving the gel its solid-like properties. In a synthetic cryogel the subunits of a polymer are mixed with a polymerising agent, but at concentrations too dilute to promote polymerisation. During highly controlled freezing, water freezes into pure ice crystals, and in the surrounding liquid the concentration of the polymerising agent increases until polymerisation occurs around the ice crystals. Upon thawing, the gel acquires some unusual properties such as shape memory, the ability to be dried and rehydrated without damage, and the gel has large interconnected pores through it. The first stage of this project created cryogels from a range of both synthetic polymers and, using a slightly different approach using cross-linking, of biological polymers such as proteins and polysaccharides. Both mechanical and physicochemical testing showed some of these gels to be unstable and unsuitable, but others performed well- in particular the cryogels made from gelatin and gelatin/fibrinogen mixes. Later work showed us how to modify the porous structure of these gels, for instance by including microbeads, or freezing in water/acetone mixes, so that pore wall thickness could be tuned to required dimensions. We were also able to incorporate carbon cloth, or more usefully, carbon microbeads into the cryogels without significant loss- allowing a material to be developed which could, for instance, adsorb odour from an infected wound. We developed a method for studying primary skin cell integration into the cryogel in cell culture. Primary cells are those taken directly from a person, and grown without modification. A three-dimensional microscopy technique allowed visualisation of integration of three skin cell types into the cryogels, and this proved to be successful, particularly in the gelatin cryogels. The success was monitored in terms of depth of ingress as well as a lack of pro-inflammatory cytokine production, and production of an extracellular matrix. These cryogels were then tested against an in vitro skin model, in which the layers of the skin were similar to those in intact skin, and good biocompatibility was achieved. Finally, we were able to perform a pilot pre-clinical test on real wounds, and while not conclusive, it was clear that the cryogels became incorporated into the regenerating tissue, and degraded, at an earlier stage than existing controls. Thus biological cryogels hold considerable promise as a matrix and a wound dressing for the future.

Data: CORDIS, © European Union