Enhanced Cryoprecipiate in Wound Healing

DESCRIPTION (provided by applicant): In wound repair, fibrin has a multiplicity of activities, some of which are intrinsic to the protein itself and some attributable to other blood constituents associated with the fibrin clot. Fibrin sealants, which have been approved for hemostasis in the US and Europe, are occasionally used on wounds to promote healing. However, inconsistency exists in the literature regarding the benefits of these preparations in the healing process. More crude fibrinogen preparations, such as cryoprecipitate made from patient's own blood on location, appear to have better utility in wounds than more purified fibrinogen preparations available through commercial sources. These divergent outcomes are likely attributable to additional blood-derived products being associated with cryoprecipitate compared to the relatively purified commercial fibrinogen based products. Clearly standard preparations and methods of application of cryoprecipitate need to be defined for each particular setting to resolve the many ostensible discrepancies. Patients with extensive wounds and burns often require skin grafts for healing to occur. At present, these defects are healed using a patient's own skin taken from another part of the body, termed a split thickness skin graft. Adhesion, revascularization and reepithelialization of these grafts are of great importance for graft survival and are the focus of the proposed study. In practice, rates of graft failure are variable and depend greatly on patient health and extent of injury. The goal of this study is to find out if the topical application of enhanced cryoprecipitate can significantly increase wound healing and thus provide a means to decrease patient morbidity and mortality, and the need for repeated grafting procedures. Cryoprecipitate is a commonly used blood product for the treatment of hemophilia to allow formation of blood clots, or in the acute trauma setting for resuscitation. It contains blood clotting factors and proteins that aid in the wound healing process. The research is focused in learning if the addition of cryoprecipitate may improve the wound "take" or reepithelialization. We propose in Phase I to complete the following specific objective: 1. To isolate and prepare the enhanced cryoprecipitate from plasma to be used as a product for wound healing/skin grafting 2. To determine wound healing in a normal donor site skin graft protocol by utilizing the combination of a hydrophilic dressing and enhanced cryoprecipitate as a dressing to promote earlier reepithelialization. Wound healing will be assessed by macroscopic and histological examination. Currently, wound repair heavily relies on the grafting of healthy skin graft harvested from a healthy donor site of the patient. This procedure is limited to donor site availability, secondary deformities, risk of disease/infection spread etc. Fibrin glue and platelet gels have also been used to help wound healing. However, fibrin glue is bioactively passive in that it does not possess a mechanism to actively recruit undifferentiated cells into its scaffolding and thus can result in delayed and defective tissue repair. Likewise platelet gels have an issue of low number of surviving platelet in the gel. Cryoprecipitate derived from patients own blood have shown a great promise in wound healing and repair without any associated secondary issues. The goal of this proposal is to test the efficacy and healing property of the enhanced cryoprecipitate on extensive wound. The ultimate goal is to translate this product into clinical use for treating patients with extensive wound and burns by evaluating the use of enhanced cryoprecipitate in Phase II studies.