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。但是，由于目前可用的DR缺乏引导细胞浸润的独特提示，因此它们可能失败 适当地进行血管化。该领域进步的关键障碍是创建一个脚手架，即1）促进快速 在全厚度伤口中，新肤色形成所需的细胞浸润和血管生成，2） 在典型/健康的伤口和难以治愈部位的事件和愈合的事件和质量增加。 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。 我们的初步数据表明，当前的Dermisphere™公式将支持所有这些未经临床 方案。我们已经在全厚性皮肤损失的猪模型中证明了Dermisphere™成功 在简单地应用两个组件时，支撑完全厚度的皮肤移植（STSG）。 此外，具有全厚度皮肤损失的小动物模型表明，Dermisphere™支持快速和 在 伤口床，有血管部分，能够使最大3毫米厚的模板血运重建。我们最近有 购买了Dermisphere™真皮再生模板公式，以使用CGMP材料设计冻结 基于最终消毒的公式，在我们的技术转移到合同中正在快速进步 制造组织。直接到II阶段SBIR的总体目标是完成一个有能力的， 临床相关的大型动物研究（AIM 1），在挑战伤口中筛选Dermisphere™产品（AIM 2）， 进行生物相容性测试（AIM 3），并进行用户验证研究（AIM 4）。这些目标的完成 Dermisphere™技术将晋升为510（k）批准，并在人类研究中提高。