The objective of the proposed Phase I SBIR is to develop and evaluate the ability of a novel regenerative collagen matrix (RCM) to prevent scarring and contracture while promoting regeneration in burn wounds. Scarring and contracture of burn wounds are very common and can lead to loss of tissue functionality and severely compromised tissue aesthetics. Current dermal substitutes have not been significantly effective in minimizing scarring and contracture in burn wounds. The standard of care includes massage, pressure therapies, steroids, silicone dressings, and additional surgeries to manage the scar and contracture burden. All current therapies aim to manage scarring and contracture after healing. The critical barrier to progress in the field is the lack of a wound dressing capable of intervening at the cellular level from the beginning of the healing process to prevent scarring and contracture. To this end, the proposed RCM incorporates enhanced architectural features and reinforced physical, chemical and biological parameters to achieve a wound dressing suitable for application early in the treatment process and with the ability to prevent scarring an contracture while promoting regeneration in burn wounds. Physical reinforcement will provide stress shielding to the cells that minimizes unchecked wound firboproliferation that leads to scarring and contracture. This is achieved by combining two physical forms of collagens within the RCM. Chemical reinforcement through crosslinking of the collagen will increase in vivo half-life by making the collagen more resistant to enzymatic degradation in the wound milieu. Biological reinforcement through heparin immobilization will induce regeneration because of heparin's ability to sequester growth factors within the RCM and optimally present them to the cells that potentiates their effects. The proposed RCM's novel bi-modal architecture will exhibit (1) a random open pore scaffold to facilitate cellular migration and intercellular interaction withn the matrix and (2) oriented micro-channels to provide a micro- niche topography for keratinocytes to enhance their proliferative phenotype and synthesis of the basement membrane proteins. This bi-modal architecture of the proposed RCM plays a vital role in providing the necessary stimuli for the wound invading cells to promote regeneration rather than scarring. RCM will undergo extensive in vitro characterization to ensure that all Phase I design specifications are satisfied after sterilization. In vitro feasibility assessments will include colagen denaturation temperature, degradation time, heparin bioactivity and pore size distribution. In vivo testing will be performed using a standard swine burn model to determine initial efficacy and preliminary biocompatibility of RCM over the course of one and three months with biopsies collected at specified time points for histological wound evaluations. If the proposed Phase I is successful, then a Phase II SBIR proposal will be submitted with the objective to realize a commercialization path by conducting pre-clinical studies aimed to determine efficacy and safety as described in the FDA's "Guidance for Industry: Chronic Cutaneous Ulcer and Burn Wounds- Developing Products for Treatment".
Public Health Relevance Statement:
Public Health Relevance: The objective of the proposed Phase I SBIR is to develop and evaluate the ability of a novel regenerative collagen matrix (RCM) to prevent scarring and contracture while promoting regeneration in burn wounds. Scars and contracture compromise the regeneration of the burn wound tissue to its original functionality and aesthetics. The current standard of care is to largely manage scars and contractures only after healing has occurred. In contrast, the proposed RCM incorporates enhanced novel architectural features and reinforced physical, chemical and biological parameters to prevent scarring and contracture before healing has occurred to enable optimal functional and aesthetic recovery of the wounded tissue.
Project Terms:
Acute; Address; Adverse reactions; Age; Aluminum; Animals; Architecture; Area; Back; base; Basement membrane; Biological; Biological Assay; biomaterial compatibility; Biopsy; Burn injury; Carbodiimides; Cattle; cell motility; Cells; Chemicals; Chronic; Cicatrix; Clinical; cold temperature; Collagen; Collagen Fibril; Collagen Type I; commercialization; Computers; Contracts; Contracture; crosslink; Cutaneous; Dermal; design; Development; Differential Scanning Calorimetry; digital; Dimensions; Ensure; Enzymes; Esthetics; Ethylene Oxide; Evaluation; Exhibits; Family suidae; Fascia; Foreign-Body Giant Cells; Freeze Drying; Gases; Goals; Growth Factor; Half-Life; Healed; healing; Heating; Heparin; Hour; Image; Immobilization; immunoreactivity; In Vitro; in vivo; Industry; Inflammation; Invaded; keratinocyte; Lead; Massage; meetings; Membrane Proteins; Microscopy, Electron, Scanning; Modeling; Molds; Monitor; Muscle; Natural regeneration; neovascularization; novel; Operative Surgical Procedures; Phase; Phenotype; Play; preclinical study; pressure; prevent; prisma; Process; Psychological reinforcement; public health relevance; Publishing; Reaction; Recovery; regenerative; Resistance; Role; Safety; scaffold; Side; Silicones; Small Business Innovation Research Grant; Specific qualifier value; standard of care; Sterile coverings; Sterilization; Steroid therapy; Stimulus; Stress; System; Temperature; Testing; Thick; Time; tissue regeneration; Tissues; Ulcer; Validation; wound; Wound Healing
