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。 然而，由于目前可用的 DRS 缺乏引导细胞浸润的独特线索，因此它们可能会失败。 充分血管化是该领域取得进展的关键障碍是创建一个支架，1）促进快速。 全层伤口中新真皮形成所需的细胞浸润和血管生成，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。 我们的初步数据表明，当前的 DermiSphere™ 配方将支持所有这些未满足的临床需求 我们已经在猪的全层皮肤损失模型中成功证明了 DermiSphere™。 支持同时应用两种成分时的完整分层皮肤移植 (STSG)。 此外，全层皮肤损失的小动物模型表明 DermiSphere™ 支持快速和 持续的横向和垂直细胞侵袭，导致在具有挑战性的病例中成功进行 STSG“采取” 我们最近拥有具有无血管部分的伤口床，并且能够对厚度达 3 毫米的模板进行血运重建。 使用 cGMP 材料将 DermiSphere™ 真皮再生模板配方用于设计冷冻 基于最终灭菌的配方，并且我们在技术转让到合同方面正在快速进展 直接进入第二阶段 SBIR 的总体目标是完成一个有动力的、 临床相关的大型动物研究（目标 1），在具有挑战性的伤口中筛选 DermiSphere™ 产品（目标 2）， 进行生物相容性测试（目标 3），并进行用户验证研究（目标 4）。 将导致 DermiSphere™ 技术取得 510(k) 批准并首次在人体研究中取得进展。