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.

项目概要/摘要 由于真皮无法自行再生，大面积全层皮肤损失无法恢复 当然，当前的黄金标准治疗涉及自体组织移植，其中患者充当。 他们自己的供体，由于全层皮肤供体部位和供体的可用性有限，这可能具有挑战性 真皮替换支架 (DRS) 旨在重建真皮，从而防止伤口。 作为无细胞产品，它们充当细胞从伤口床渗透的支架， 组织成功能性的、血管化的新真皮组织，能够支撑作为皮肤移植物植入的皮肤移植物 第二步程序，导致伤口愈合并具有正常的皮肤真皮/表皮结构。 由于目前可用的 DRS 缺乏引导此类细胞浸润的独特线索，因此它们可能无法血管化 该领域取得进展的关键障碍是创建一个支架，1）促进快速细胞生长。 全层伤口中新真皮形成所需的浸润和血管生成，以及 2) 增加 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™，这是一种创新型药物 DRS 产品可使全层皮肤脱落伤口的真皮再生速度更快（≤7 天，即速度>75%） 比使用市场领先的 DRS 产品 Integra® 实现的再生效果要好得多。 它可以覆盖一层薄薄的自体表皮移植物，使皮肤更加柔韧、功能性和弹性 与仅使用分层皮肤移植愈合的伤口相比，DermiSphereTM 的商业化有望实现。 改善全层皮肤缺损常见的外科领域的临床实践，包括但不限于 外伤、烧伤、感染和肿瘤后重建手术，通过显着减少时间 在大量全层皮肤损失的情况下实现伤口愈合所需的时间，这将直接导致 减少患者痛苦并减少宝贵的医疗保健资源的支出。 该商业准备试点（CRP）的目标是完成后期开发并启用 Fesarius 获得 510(k) 许可，开发 DermiSphereTM 的规模化制造能力。 产品是实现大规模生产必须克服的最重要的障碍之一 这项有前途的技术的临床影响 该拟议项目的具体目标是 (1) 建立和 验证符合 cGMP 的制造工艺，该工艺将为 DermiSphereTM 产品做好准备 商业发布 (2) 设计和验证 DermiSphereTM 产品的包装并验证灭菌； (3) 对 DermiSphereTM 及其阻隔包装进行完整的实时和加速稳定性验证；以及 (4) 提交 510(k) 申请并获得 FDA 的许可。