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

STTR I 期开发用于糖尿病皮肤伤口愈合的新型抗菌和抗真菌生物粘附生物材料

• 批准号: 9909142
• 负责人: Maoqi Mark Feng
• 金额: $ 22.5万
• 依托单位: DYNAMIC ENTROPY TECHNOLOGY, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909142
• 关键词: Acids; Adhesions; Allografting; Animals; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Biocompatible Materials; Biological; Biological Assay; Businesses; Cells; Citrates; Collagen; Complex; Cutaneous; Decubitus ulcer; Deposition; Dermal; Development; Devices; Diabetes Mellitus; Diabetic Foot Ulcer; Diabetic mouse; Diabetic ulcer; Diabetic wound; Encapsulated; Entropy; FDA approved; Face; Funding; Future; Goals; Health; Hydrolysis; In Vitro; Infection; Infection prevention; Injectable; Ions; Lead; Legal patent; Mechanics; Medical Device; Modeling; Morbidity - disease rate; Mussels; Mycoses; National Institute of Diabetes and Digestive and Kidney Diseases; Osteomyelitis; Patients; Pennsylvania; Pharmaceutical Preparations; Phase; Physical condensation; Polymers; Positioning Attribute; Process; Property; Reaction; Reproducibility; Research; Safety; Sepsis; Severities; Shapes; Silver; Skin; Skin wound; Spinal cord injury; Sterile coverings; Structural Protein; Technology; Technology Transfer; Testing; Tissue Adhesives; Tissues; Universities; Wound Healing; Wound Infection; adhesive polymer; antimicrobial; base; biomaterial compatibility; biomaterial development; collagenase; commercialization; crosslink; diabetic; diabetic patient; diabetic wound healing; foot; fungus; healing; improved; in vivo; innovation; mechanical properties; microbial; mortality; novel; off-patent; phase 2 study; protein structure; success; wound; wound closure

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.

摘要 糖尿病溃疡或压疮在糖尿病、脊髓损伤等患者中很常见。 如果没有适当的处理，这种伤口往往会导致骨髓炎或败血症等感染， 导致高死亡率和高发病率。除了细菌感染，糖尿病患者还 也更容易受到皮肤真菌感染。先进的伤口敷料和先进的 当感染的严重程度发生在糖尿病溃疡甚至是溃疡时，应采用伤口治疗。 压疮。 本项目旨在开发新型胶原蛋白-柠檬酸盐基聚合物生物材料医疗器械 这可能会在皮肤伤口愈合方面找到应用，特别是在挑战糖尿病皮肤伤口方面。 治愈。我们的生物材料医疗设备在双重降解方面可能是独一无二的 机制(酶和水解)，比生物同种异体移植更好的重复性， 可持续的抗真菌药物作为降解产品释放，无缝合伤口由于 组织粘附力强，生物相容性好等。它是建立在PSU的专利柠檬酸盐- 基于聚合物粘合剂和Det独特的胶原蛋白电化学沉积工艺。在……里面 目标1，至少5种不同组成的交联型胶原-柠檬酸盐基聚合物 准备好了。将对合成的胶原-柠檬酸盐聚合物生物材料进行表征和筛选。 用于抗菌性能、组织粘附性、细胞生物兼容性、体外降解性 (胶原酶降解法和水解法)和机械性能。一位领先者 将确定以胶原-柠檬酸盐为基础的聚合物创面基质。在目标2中，提议领导 基于胶原-柠檬酸盐的聚合物基质将在糖尿病多菌感染的皮肤上进行测试 将伤口模型与FDA批准的胶原伤口基质和其他对照进行比较。我们 预计所提出的新型胶原-柠檬酸盐聚合物基质可能会显著加速 与对照组相比，感染的糖尿病皮肤伤口的愈合情况。第一期工程的成功之处 可能导致一种基于胶原-柠檬酸盐的聚合物基质定位于第二阶段研究，这将 导致先进的伤口疗法，以减轻糖尿病皮肤伤口的健康负担 即使是普通的皮肤伤口。