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

DermiSphere™：用于重建手术 (CRP) 的先进真皮再生支架

• 批准号: 10698334
• 负责人: Yulia Sapir Lekhovitser
• 金额: $ 39.97万
• 依托单位: FESARIUSTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10698334
• 关键词: Acceleration; Address; Architecture; Area; Autologous; Autologous Transplantation; Biological Assay; Burn injury; Care given by nurses; Cattle; Cells; Cellular Infiltration; Clinical; Collagen; Complication; Contracture; Cues; Cyclic GMP; Dermal; Dermis; Development; Devices; Engineering; Ensure; Expenditure; Failure; Healthcare; Human; Hydration status; Immobilization; Impaired wound healing; Implant; Incidence; Infection; Infiltration; Life; Marketing; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Patients; Performance; Preclinical Testing; Preparation; Procedures; Process; Production; Protocols documentation; Qualifying; Readiness; Reconstructive Surgical Procedures; Reporting; Resources; Site; Skin; Skin graft; Specific qualifier value; Sterilization; System; Technology; Tendon structure; Testing; Therapeutic; Thick; Thinness; Time; Tissues; Trauma; United States Centers for Medicare and Medicaid Services; Validation; Vascularization; Viral; angiogenesis; clinical practice; commercialization; design; flexibility; healing; implantation; improved; infection risk; innovation; instrument; manufacture; manufacturing capabilities; manufacturing process; microbial; prevent; product development; prototype; resilience; response; scaffold; standard care; wound; wound bed; wound healing

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.

项目摘要/摘要 由于真皮无法自行再生，因此无法恢复大量全厚的皮肤损失 自然。当前的黄金标准治疗涉及自动组织转移，其中患者用作 他们自己的捐助者，由于有限的全厚皮肤供体站点和捐赠者的供体可能会受到挑战。 现场发病率。真皮替换脚手架（DRS）的目的是重现真皮，从而防止伤口 收缩。作为无细胞的产品，它们是从伤口床中渗入细胞的脚手架 组织到功能性的，血管化的新病组织，能够支撑植入的皮肤移植物 第二步过程，导致皮肤正常皮肤/表皮结构愈合的伤口。然而， 由于目前可用的Drs缺乏引导这种细胞浸润的独特提示，因此它们可能无法血管化 足够。该领域进步的关键障碍是创建一个脚手架，即1）促进快速细胞 在全厚性伤口中，新肤色形成所需的浸润和血管生成，2）增加 典型/健康的伤口的发生率和愈合质量，难以治愈部位。 为了解决这一重大临床差距，Fesarius Therapeutics，Inc。正在开发Dermisphere™，这是一种创新的 DRS产品将使皮肤损失全厚的真皮再生真皮（≤7天，即快75％） 比使用市场领先的DRS产品Integra®实现的再生。一旦真皮再生 它可以用薄薄的表皮皮肤自体移植覆盖，产生更灵活，实用和弹性的皮肤 比仅用厚度分裂的皮肤移植物愈合的伤口。预计皮肤化的商业化 在外科手术领域中改善临床实践，其中完全厚度皮肤的损失很常见，包括但不限 通过大大减少时间，创伤，烧伤，感染和肿瘤后重建手术 在厚度大的皮肤损失的情况下，需要实现可愈合的伤口，这将直接导致 减少患者痛苦以及降低宝贵医疗保健资源的支出。 这个商业准备飞行员（CRP）的目的是完成后期开发并启用 fesarius可以达到510（k）清除。开发皮肤表的缩放制造能力 产品是必须克服的最重要障碍之一，以实现广泛的规模 这项承诺技术的临床影响。该拟议项目的具体目的是（1）建立和 验证CGMP兼容的制造过程，该工艺将为Dermispheretm产品准备 商业发行（2）设计和验证包装和验证皮肤表产品的灭菌； （3）针对皮肤表及其屏障包装的完整实时和加速稳定性验证； （4） 提交510（k）申请并从FDA获得许可。