DermiSphere™: An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery, CRP

项目概要/摘要 由于真皮无法自行再生，大面积全层皮肤缺损无法恢复 自然.目前的金标准治疗涉及自体组织移植，其中患者作为 他们自己的供体，这可能是具有挑战性的，由于有限的可用性全厚度皮肤供体网站和供体， 现场发病率。真皮替代支架（DRS）旨在重建真皮，从而防止伤口 收缩。作为无细胞产物，这些用作细胞从伤口床浸润的支架， 组织成功能性的血管化新真皮组织，能够支持作为移植物植入的皮肤移植物。 第二步手术，导致具有正常皮肤真皮/表皮结构的愈合伤口。然而，在这方面， 由于目前可用的DRS缺乏引导这种细胞浸润的独特线索，它们可能无法血管化 足够了在这一领域取得进展的关键障碍是创造一种支架，1）促进快速细胞增殖， 在全层伤口中新真皮形成所需的浸润和血管生成，和2）增加了 典型/健康伤口和难以愈合部位的愈合发生率和质量。 为了解决这一重大临床差距，Fesarius Therapeutics，Inc.正在开发DermiSphere™，一种创新的 DRS产品可更快地再生全层皮肤缺损伤口中的真皮（≤7天，即>75%） 比使用市场领先的DRS产品Integra®实现的再生效果更好。一旦真皮再生 它可以覆盖一层薄的自体表皮，使皮肤更柔韧，功能更强，更有弹性 比单独使用中厚皮片愈合的伤口要好。DermiSphere ™的商业化有望 以改善全层皮肤缺损常见的外科领域中的临床实践 创伤、烧伤、感染和肿瘤重建手术后， 需要在大面积全层皮肤缺损的情况下实现伤口愈合，这将直接导致 减少患者的痛苦以及降低宝贵的卫生保健资源的支出。 商业就绪试点（CRP）的目标是完成后期开发， Fesarius获得510（k）批准。开发DermiSphere？的规模化生产能力 产品是实现大规模生产必须克服的最重要的障碍之一。 这一有前途的技术的临床影响。本项目的具体目标是：（1）建立和 确认cGMP兼容的生产工艺，该工艺将制备DermiSphere？产品， 商业发布（2）设计和确认包装，并确认DermiSphere？产品的灭菌; (3)完成DermiSphere TM及其屏障包装的实时和加速稳定性验证;以及（4） 提交510（k）申请并获得FDA的批准。

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. Being cell-free products, these serve as a scaffold for the infiltration of cells from the wound bed that organize to a functional, vascularized neodermis tissue, able to support a skin graft which is implanted as a second step procedure, resulting in a healed wound with normal skin dermal/epidermal architecture. However, because currently available DRS lack unique cues to guide such 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. The objective of this Commercial Readiness Pilot (CRP) is to complete late-stage development and enable Fesarius to achieve 510(k) clearance. Development of scaled manufacturing capabilities of the DermiSphereTM product represents one of the most important obstacles that must be surmounted in order to achieve broad-scale clinical impact of this promising technology. The Specific Aims for this proposed project are to (1) Establish and validate a cGMP-compatible manufacturing process which will prepare the DermiSphereTM product for commercial release (2) Design and validate packaging and validate sterilization of the DermiSphereTM product; (3) Complete real-time and accelerated stability validation for DermiSphereTM and its barrier packaging; and (4) Submit the 510(k) application and obtain clearance from the FDA.