An Advanced Dermal Regeneration Scaffold for Reconstructive Surgery

用于重建手术的先进真皮再生支架

• 批准号: 10760482
• 负责人: Yulia Sapir Lekhovitser
• 金额: $ 88.39万
• 依托单位: FESARIUSTHERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10760482
• 关键词: Address; Anatomy; Animal Model; Animals; Autologous; Autologous Transplantation; Burn injury; Care given by nurses; Cells; Cellular Infiltration; Clinical; Complication; Contracts; Contracture; Cues; Cyclic GMP; Data; Dermal; Dermis; Engineering; Esthetics; Excision; Expenditure; Formulation; Freezing; Healthcare; Human; Hypertrophic Cicatrix; Immobilization; Impaired wound healing; Incidence; Infection; Infiltration; Intention; Interview; Invaded; Lateral; Marketing; Morbidity - disease rate; Natural regeneration; Operative Surgical Procedures; Outcome; Patients; Performance; Phase; Procedures; Process; Reconstructive Surgical Procedures; Resources; Site; Skin; Skin graft; Small Business Innovation Research Grant; Surgeon; Technology; Technology Transfer; Tendon structure; Testing; Therapeutic; Thick; Thinness; Time; Tissues; Trauma; Validation; Vascularization; Work; angiogenesis; biomaterial compatibility; clinical practice; clinically relevant; commercialization; design; design verification; first-in-human; flexibility; healing; improved; infection risk; innovation; manufacturing organization; porcine model; prevent; product development; regenerative; resilience; scaffold; standard care; validation studies; 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. 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.

项目总结/摘要 由于真皮不能自行再生，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。然而，由于目前可用的DRS缺乏引导细胞浸润的独特线索， 使血管充分扩张在这一领域取得进展的关键障碍是创造一个支架，1）促进快速 在全层伤口中新皮肤形成所需的细胞浸润和血管生成，和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™，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。 我们的初步数据表明，目前的DermiSphere™制剂将支持所有这些未满足的临床 场景我们已经在全层皮肤缺损的猪模型中证明，DermiSphere™ 当两种成分同时应用时，支持全层皮肤移植（STSG）。 此外，全层皮肤缺损的小动物模型显示，DermiSphere™支持快速和 持续的横向以及垂直细胞浸润，导致成功的STSG“采取”在具有挑战性的情况下， 无血管部分的伤口床，并且能够使高达3 mm厚的模板再血管化。我们最近 将DermiSphere™真皮再生模板配方用于使用cGMP材料设计冷冻 基于最终灭菌的配方，并且在我们的技术转让合同中进展迅速 制造组织。本直接至第二阶段SBIR的总体目标是完成一个动力， 临床相关的大型动物研究（目标1），在挑战性伤口中筛选DermiSphere™产品（目标2）， 进行生物相容性试验（目标3），并进行用户确认研究（目标4）。完成这些目标 将推动DermiSphere™技术获得510（k）批准，并首次用于人体研究。