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

项目摘要/摘要 由于真皮不能自行再生，大面积的全层皮肤损失无法修复。 当然。目前的黄金标准治疗包括自体组织移植，其中患者充当 他们自己的供体，这可能是具有挑战性的，因为可获得的全层皮肤供体部位和供体- 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。这些都是无细胞的产品，可以作为细胞从伤口床渗入的支架 组织成功能性的、血管化的新生真皮组织，能够支持作为植入物的皮肤移植 第二步手术，导致愈合的伤口具有正常的皮肤真皮/表皮结构。然而， 由于目前可用的DRS缺乏引导这种细胞渗透的独特信号，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，它能促进快速的细胞 全层创面中新生真皮形成所需的渗透和血管生成，以及2)增加 在典型/健康伤口和难愈合部位的发生率和愈合质量。 为了解决这一重大的临床差距，Fesarius Treateutics，Inc.正在开发一种创新的DERMISPERE™ DRS产品，可以更快地在全层皮肤剥离创面再生真皮(≤7天，即快75%) 比使用市场领先的DRS产品Integra®实现的再生更好。一旦真皮再生 它可以被薄薄的自体表皮皮肤覆盖，产生更具弹性、功能性和弹性的皮肤。 比仅用中厚皮片移植愈合伤口要好。DermiSphereTM有望商业化 改善外科领域的临床实践，其中包括但不限于全层皮肤剥离 通过显著减少时间，减少创伤、烧伤、感染和肿瘤重建手术后 在大面积全层皮肤脱落的情况下实现伤口愈合所需的，这将直接导致 减少了病人的痛苦，并降低了宝贵的医疗资源的支出。 此商业就绪性试点(CRP)的目标是完成后期开发并实现 费萨里厄斯要实现510(K)通关。开发DermiSphereTM的规模化制造能力 产品是最重要的障碍之一，必须克服才能实现广泛的 这项前景看好的技术的临床影响。这项拟议项目的具体目标是：(1)建立和 验证兼容cGMP的制造流程，该流程将为以下项目准备DermiSphereTM产品 商业发布(2)设计和验证包装以及验证DermiSphereTM产品的灭菌； (3)对DermiSphereTM及其阻隔包装进行完全实时和加速的稳定性验证；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.