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

这个小型企业技术转移(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床疮或压疮(PU)。每年有超过250万美国人，通常是老年人，遭受脓液的折磨。脓液可以是很深的伤口，需要几个月的时间才能痊愈，会引起巨大的疼痛；如果感染，它们可能会导致败血症和死亡。据估计，美国每年用于治疗所有脓液的费用超过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，但由于感染或移植物不够坚固，这种方法可能无法治愈压迫性溃疡。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，这种替代品有利于再生，强度更高，并在手术部位释放抗感染药物，以实现愈合。这可能使治疗II-III期脓肿(占所有脓肿的58%)的医生和医院受益；3年市场潜力超过1.5亿美元。拟议解决方案的基础技术可用于制造用于治疗多种伤口类型的新型移植物，提高愈合和患者的生活质量。这个小企业技术转移(STTR)第一阶段项目重点展示了这种装载药物、聚合物浸渍的脱细胞生物移植物(ABG)平台技术的可行性。目前，脓液是使用皮肤或皮肤替代物(如ABG)进行手术重建的，这些移植通常由于感染或缺乏机械强度而失败。通过在ABG中嵌入聚合物水凝胶，可以对其进行机械加固。此外，将聚合物与药物(药物+聚ABG)混合，可以实现药物输送系统，在14天内提供持续的局部释放治疗药物，如抗感染药物。这一新的方法同时为患者介导的组织再生提供了同种异体支架，并防止了伤口愈合过程中常见并发症的发生。这种用于治疗应用的ABG生物相容性聚合物浸渍以前从未进行过。这个第一阶段的项目将通过(1)表征药物释放和体外生物活性以及(2)在局部MRSA挑战下对单期重建II-III期脓肿的体内小鼠模型进行疗效评估来证明药物+PolyABG的可行性。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.