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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的糖尿病性溃疡或压疮对于糖尿病，脊髓损伤等患者常见。没有适当的治疗，此类伤口通常会导致感染，例如骨髓炎或败血症，导致高死亡率和发病率。除了细菌感染外，糖尿病患者是也更容易受到皮肤真菌感染的影响。高级伤口敷料和高级敷料由于感染的严重程度发生在糖尿病性溃疡甚至压疮。该项目旨在开发新颖的基于胶原蛋白的聚合物生物材料医疗设备这可能会发现皮肤伤口愈合中的应用，尤其是在挑战糖尿病皮肤伤口中康复。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理（酶促和水解），比生物学分别更好的可重复性，可持续的抗真菌药物作为退化产物发布，由于强大的组织粘附和出色的生物相容性等。它是基于PSU专利的柠檬酸盐建造的基于聚合物粘合剂和DET独特的胶原蛋白电化学沉积过程。在 AIM 1，至少5种不同组合物的基于胶原蛋白的交联胶原蛋白聚合物将是准备。最终的胶原蛋白聚合物生物材料将被表征和筛选对于抗菌特性，组织粘合特性，细胞生物相容性，体外降解性（胶原酶降解测定和水解）以及机械性能。一个领先将确定基于胶原蛋白的聚合物伤口基质。在AIM 2，拟议领导基于胶原蛋白的聚合物基质将在糖尿病性多因素感染的皮肤中进行测试与FDA批准的胶原蛋白伤口基质和其他对照组相比，伤口模型。我们预期拟议的新型胶原蛋白柠檬酸聚合物基质可能会显着加速与对照组相比，感染糖尿病皮肤伤口的愈合。该阶段ISTTR的成功可能导致基于胶原蛋白的聚合物基质，该聚合物基质定位为II期研究，该基质将导致先进的逻辑疗法，以减少糖尿病皮肤伤口的健康灼伤和即使是常规的皮肤伤口。