STTR Phase I Development of Novel Antibacterial and Antifungal Bioadhesive Biomaterials for Diabetic Skin Wound Healing

摘要 糖尿病性溃疡或压力性溃疡在糖尿病、脊髓损伤等患者中很常见。 如果没有适当的处理，这种伤口通常会导致感染，如骨髓炎或败血症， 导致高死亡率和发病率。除了细菌感染，糖尿病患者 也更容易受到皮肤真菌感染。高级伤口敷料和高级 当感染的严重程度发生在糖尿病溃疡或甚至 压迫性溃疡 本项目旨在开发新型胶原-柠檬酸盐基高分子生物材料医疗器械 其可应用于皮肤伤口愈合，特别是具有挑战性的糖尿病皮肤伤口， 治愈我们的生物材料医疗器械在双重降解方面具有潜在的独特性 机制（酶促和水解），比生物同种异体移植物更好的再现性， 作为降解产物释放的可持续抗真菌药物， 组织附着力强，生物相容性好等特点。 基于聚合物粘合剂和DET独特的胶原电化学沉积工艺。在 目的1，将制备至少5种不同组成的交联的基于胶原-柠檬酸盐的聚合物。 制备将对所得胶原-柠檬酸盐聚合物生物材料进行表征和筛选 用于抗菌性能、组织粘合性能、细胞生物相容性、体外降解性 （胶原酶降解测定和水解）和机械性能。一位知名 将确定基于胶原-柠檬酸盐的聚合物伤口基质。在目标2中，建议领导 将在糖尿病多微生物感染的皮肤中测试基于胶原-柠檬酸盐的聚合物基质 伤口模型与FDA批准的胶原伤口基质和其他对照相比。我们 预期所提出的新型胶原-柠檬酸盐聚合物基质可显著加速 与对照相比，感染的糖尿病皮肤伤口的愈合。第一阶段STTR的成功 可能导致胶原-柠檬酸盐基聚合物基质定位于II期研究， 导致一种先进的伤口治疗，用于减少糖尿病皮肤伤口的健康负担， 即使是普通的皮肤伤口

Abstract Diabetic ulcers or pressure ulcers are common for patients with diabetes, spinal cord injuries, etc. Without proper management, such wounds often lead to infections such as osteomyelitis or sepsis, resulting in high mortality and morbidity. In addition to bacterial infection, diabetic patients are also more susceptible to cutaneous fungal infections. Advanced wound dressings and advanced wound therapies should be employed as the severity of infection occurs in diabetic ulcer or even pressure ulcer. This project aims to develop novel collagen-citrate-based polymer biomaterial medical devices which may find applications in skin wound healing, especially in challenging diabetic skin wound healing. Our biomaterial medical devices are potentially unique in terms of dual degradation mechanism (enzymatic and hydrolysis), better reproducibility than biological allografts, sustainable anti-fungal drug released as a degradation product, sutureless wound closure due to strong tissue adhesion, and excellent biocompatibility, etc. It is built upon PSU’s patented citrate- based polymer adhesive and DET’s unique collagen electrochemical deposition process. In Aim 1, crosslinked collagen-citrate-based polymer of at least 5 different compositions will be prepared. The resultant collagen-citrate polymer biomaterials will be characterized and screened for antimicrobial properties, tissue adhesive properties, cell biocompatibility, in-vitro degradability (Collagenase degradation assay and hydrolysis), and mechanical properties. One leading collagen-citrate based polymer wound matrix will be determined. In aim 2, Proposed leading collagen-citrate based polymer matrix will be tested in a diabetic polymicrobial infected skin wound model compared to an FDA-approved collagen wound matrix and other controls. We expect that proposed novel collagen-citrate polymer matrix may significantly accelerate the healing of infected diabetic skin wounds compared to controls. The success of this Phase-I STTR may lead to a collagen-citrate based polymer matrix positioned for a Phase II study, which will lead to an advanced wound therapy for reduce the health burden of diabetic skin wounds and even regular skin wounds.