STTR Phase I: Novel Acellular Grafts Containing Rifampin and Minocycline for Single-Stage Reconstruction of Stage II-III Pressure Ulcers

STTR 第一期：含有利福平和米诺环素的新型脱细胞移植物，用于 II-III 期压疮的单阶段重建

• 批准号: 2012920
• 负责人: Nicholas Pashos
• 金额: $ 25.12万
• 依托单位: BIOAESTHETICS CORPORATION
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-15 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2012920&HistoricalAwards=false
• 关键词: STTR; Phase; Novel; Acellular; Grafts

The broader impact /commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to develop a wound care product to heal bed sores or pressure ulcers (PUs). Over 2.5 million Americans, usually older adults, suffer from PUs annually. PUs can be deep wounds, take many months to heal, cause significant pain; if infected, they can lead to sepsis and death. The annual U.S. cost for treatment of all PUs is estimated to be greater than $11 billion. Current treatment options involve surgical reconstruction with skin or skin substitute grafts, which can fail to heal the pressure ulcer because of infection or because the graft was not strong enough. To address these issues, the proposed project will develop a novel skin substitute that is pro-regenerative, stronger, and releases infection-fighting drugs at the surgical site to allow healing. This could benefit physicians and hospitals treating patients with stage II-III PUs (58% of all PUs); the 3-year market potential is over $150 million. The underlying technology of the proposed solution can be used to make novel grafts for treatment of numerous wound types, improving healing and patient quality of life.This Small Business Technology Transfer (STTR) Phase I project focuses on demonstrating the feasibility of this drug-loaded, polymer-impregnated acellular biologic graft (ABG) platform technology. Currently, PUs are surgically reconstructed using skin or skin substitute grafts, like ABGs, which often fail due to infection or lack of mechanical strength. By embedding a polymer hydrogel within an ABG, it can be mechanically strengthened. Furthermore, mixing the polymer with drugs (drug+polyABG) enables a drug delivery system that provides sustained, local release of therapeutic agents such as anti-infectives over a 14-day period. This novel approach simultaneously provides an allogeneic scaffold for patient-mediated tissue regeneration and counters onset of common complications during wound healing. This biocompatible polymer impregnation of ABGs for therapeutic applications has not been performed previously. This Phase I project will demonstrate feasibility drug+polyABG by (1) characterizing drug release and bioactivity in vitro and (2) assessing efficacy in an in vivo mouse model of single-stage reconstruction of stage II-III PUs challenged with topical MRSA.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业技术转让（STTR）第一阶段项目的更广泛的影响/商业潜力是开发一种伤口护理产品来治愈褥疮或压疮（PU）。每年有超过250万美国人，通常是老年人，患有PU。PU可能是深度伤口，需要数月才能愈合，引起严重疼痛;如果感染，可能导致败血症和死亡。据估计，美国每年用于治疗所有PU的费用超过110亿美元。目前的治疗方案包括用皮肤或皮肤替代移植物进行手术重建，这可能由于感染或移植物不够坚固而无法治愈压疮。为了解决这些问题，拟议的项目将开发一种新的皮肤替代品，这种替代品具有促进再生的作用，更强大，并在手术部位释放抗感染药物以允许愈合。这可能使治疗II-III期PU患者（占所有PU的58%）的医生和医院受益; 3年的市场潜力超过1.5亿美元。该解决方案的基础技术可用于制造新型移植物，用于治疗多种伤口类型，改善愈合和患者生活质量。该小企业技术转让（STTR）I期项目的重点是证明这种载药聚合物浸渍无细胞生物移植物（ABG）平台技术的可行性。目前，PU是使用皮肤或皮肤替代移植物（如ABG）进行手术重建的，这些皮肤或皮肤替代移植物通常由于感染或缺乏机械强度而失败。通过将聚合物水凝胶嵌入ABG内，可以对其进行机械强化。此外，将聚合物与药物（药物+聚ABG）混合使得药物递送系统能够在14天的时间段内提供治疗剂如抗感染剂的持续局部释放。这种新方法同时为患者介导的组织再生提供了同种异体支架，并对抗伤口愈合期间常见并发症的发生。用于治疗应用的ABG的这种生物相容性聚合物浸渍以前没有进行过。该I期项目将通过以下方式证明药物+polyABG的可行性：（1）表征体外药物释放和生物活性;（2）评估局部MRSA挑战的II-III期PU单阶段重建的体内小鼠模型的疗效。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。