An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery

PROJECT SUMMARY/ABSTRACT Due to the inability of the dermis to regenerate on its own, large full thickness skin loss cannot be restored naturally. The current gold standard treatment involves autologous tissue transfer in which the patient serves as their own donor, which may be challenging due to limited availability of full thickness skin donor sites and donor- site morbidity. Dermal Replacement Scaffolds (DRS) aim to recreate dermis, thereby preventing wound contraction. However, because currently available DRS lack unique cues to guide cell infiltration, they may fail to vascularize sufficiently. The critical barrier to progress in this field is to create a scaffold that 1) promotes rapid cellular infiltration and angiogenesis as required for neodermal formation in full thickness wounds, and 2) increases the incidence and quality of healing in both typical/healthy wounds and difficult to heal sites. To address this significant clinical gap, Fesarius Therapeutics, Inc. is developing DermiSphere™, an innovative DRS product that will regenerate dermis in full thickness skin loss wounds much faster (≤7 days, i.e. >75% faster) than the regeneration achieved using the market-leading DRS product, Integra®. Once dermis has regenerated it can be covered with a thin epidermal skin autograft, yielding skin that is more flexible, functional, and resilient than wounds healed with split thickness skin grafts alone. The commercialization of DermiSphereTM is expected to improve clinical practice in the surgical fields where full thickness skin loss is common including, but not limited to, trauma, burns, infection and post oncologic reconstructive surgery, by significantly decreasing the time required to achieve a healed wound in a scenario of large full thickness skin loss, which will directly result in decreased patient suffering as well as lower expenditure of valuable health care resources. Our preliminary data suggests that the current DermiSphere™ formulation will support all these unmet clinical scenarios. We have demonstrated in a swine model of full thickness skin loss that DermiSphere™ successfully supports complete split thickness skin graft (STSG) take when the two components are applied simultaneously. In addition, a small animal model of full thickness skin loss showed that DermiSphere™ supported rapid and sustained lateral as well as vertical cell invasion, resulting in successful STSG “take” in challenging cases of wound beds with avascular portions and was able to revascularize templates up to 3mm thick. We have recently brought the DermiSphere™ dermal regenerative template formulation to design freeze using a cGMP-material based formulation that is terminally sterilized and are fast progressing in our technology transfer to a contract manufacturing organization. The overall objective of this Direct to Phase II SBIR is to complete a powered, clinically relevant large animal study (Aim 1), screen the DermiSphere™ product in challenging wounds (Aim 2), perform biocompatibility testing (Aim 3), and perform user validation studies (Aim 4). Completion of these Aims will result in the advancement of DermiSphere™ technology towards 510(k) approval and first in human studies.