DermiSphere: An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery, PHASE II

ABSTRACT On its own, the human body is incapable of dermis regeneration. If not properly treated, large full-thickness skin wounds (loss of epidermis and dermis) heal through contraction of surrounding skin and scar formation, which may ultimately lead to chronic wounds, permanent damage, disfigurement and patient suffering. For years, the gold-standard treatment has been autologous tissue transfer (a patient serving as their own donor), but insufficient donor site availability, secondary contracture of split thickness skin grafts and major donor-site morbidity leaves surgeons wanting alternatives. In the early 2000andapos;s, engineered treatments emerged, which now have annual sales from $500MM to $1BN, growing 8-12% annually. The market leader, Integra™, has several shortcomings in both the rate and degree of healing as well as decreased effectiveness in challenging wounds. DermiSphere™, the proposed product of this application is an implantable dermal regenerative scaffold that addresses these concerns. DermiSphereandapos;s (DS) patented 3D patterned microarchitecture guides rapid cell penetration from the wound bed into the scaffold, leading to swift vascularization and neo-dermis formation. Our previous studies treated clinically-relevant rodent and pig wounds with a DS prototype, and demonstrated improved performance as compared to Integra (andgt;75% graft take vs. ~50% respectively), decreased hemorrhage, enhanced graft vitality and a 40% increase in dermal thickness. These all indicate better clinical outcomes. Completion of this Phase II proposal will result in a frozen DS design that will then be used in biocompatibility and validation testing as required for FDA 510(k) clearance. Furthermore, this frozen design will be validated for superior performance versus Integra in a clinically relevant pig full-thickness wound model. Specifically, the study will evaluate the value proposition determined during the NIH iCorps program of ≥20% improvement in graft “take” time/incidence and wound contracture vs. Integra. In Phase II, we will complete two Specific Aims 1: Design Freeze for the optimized DS. DS is two layers: a polysiloxane (silicone) layer and a type I collagen scaffold (comprised of bulk collagen and embedded collagen microspheres). This aim contains four tasks to develop the “final” version of the device meant for commercial use: (1) andamp; (2) Optimize microsphere size and crosslinking and bulk collagen using cGMP compliant collagen sources and equipment; (3) Optimize the occlusive layer for clinical use; (4) Develop terminal sterilization parameters without adversely affecting DS. The resulting prototypes will be screened for efficacy using a rat full-thickness wound model. 2: Demonstrate superiority to the market leader and meet/exceed our performance value proposition in the clinically-relevant, full-thickness excisional model in swine. An optimized DS with a frozen design that has superior efficacy over Integra in a full-scale (porcine) wound model is currently the first major strategic milestone. This will sufficiently increase the equity value of FesariusTherapeutics Inc. to attract the capital needed to scale operations for cGMP manufacturing, FDA submission and commercialization.PROJECT NARRATIVE When autologous tissue is not available or split thickness skin grafts alone are used, full-thickness skin loss may not heal or will heal by contracture of the surrounding skin resulting in unstable healed wounds that do not contain the normal epidermal/dermal architecture of healthy skin, but rather significant scar tissue formation that results in substantial functional and aesthetic impairment for the patient. Current treatment approaches including engineered “off the shelf products” have significant limitations, including slow, inconsistent, and inadequate tissue formation, hence impaired wound healing. The commercialization of DermiSphereTM is expected to improve clinical practice in surgical fields where full thickness skin loss is common including, but not limited to, trauma, burns, and post oncologic reconstructive surgery, by significantly decreasing the time required to achieve a healed wound, as well as increasing the thickness of the regenerated dermis in a scenario of (large) full thickness skin loss