Injectable microgel for soft tissue repair

用于软组织修复的可注射微凝胶

• 批准号: 8926455
• 负责人: Joseph C. Salamone
• 金额: $ 13.05万
• 依托单位: ROCHAL INDUSTRIES, LLP
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8926455
• 关键词: Adipose tissue; Adult; Affect; Area; Autologous; Biocompatible; Biocompatible Materials; Cadaver; Cattle; Cell Adhesion; Cell Survival; Cell Transplants; Cell-Cell Adhesion; Cell-Matrix Junction; Cells; Clinical; Collagen; Complication; Data; Data Collection; Decubitus ulcer; Defect; Development; Diabetes Mellitus; Evaluation; Exhibits; Family suidae; Fibrinogen; Freeze Drying; Future; Gel; Goals; Government; Grant; Growth Factor; Healed; Health; Heart Diseases; Hydrogels; In Vitro; Industry; Infection; Injectable; Injection of therapeutic agent; Investigation; Kidney Diseases; Left; Life; Manufacturer Name; Modeling; Morbidity - disease rate; Osteomyelitis; Pain; Patients; Persons; Phase; Powder dose form; Preclinical Testing; Process; Production; Property; Quality Control; Quality of life; Rattus; Recovery; Research; Safety; Septicemia; Site; Skin; Small Business Innovation Research Grant; Source; Staging; Stem cells; Sterility; Sterilization; Surface; System; Temperature; Testing; Thick; Time; Toxic effect; Treatment Cost; United States National Institutes of Health; Work; Wound Healing; aging population; amnion; angiogenesis; base; biomaterial compatibility; cell growth; cell motility; clinical application; clinical practice; commercial application; commercialization; crosslink; cytotoxicity; design; healing; implantation; improved; in vivo; injured; innovation; manufacturing process; mortality; paracrine; preclinical efficacy; preclinical safety; preclinical study; safety study; scaffold; scale up; soft tissue; stability testing; technological innovation; tissue regeneration; tissue repair; wound

DESCRIPTION (provided by applicant): Pressure ulcers are a major health problem affecting millions of adults in the USA. They can be a significant site for infection leading to complication such as septicaemia and osteomyelitis, in addition to causing significant pain and suffering, compromised quality of life, financial burden, and morbidity/mortality. In conjunction with an aging population, particularly those with diabetes, kidney disease, and heart disease, the occurrence of pressure ulcers will most likely continue to rise. There is a recognized clinical need for improved treatment of pressure ulcers, particularly those with undermining and tunneling voids. In this research an injectable matrix to safely deliver autologous cells or cellulr products into soft tissue defects or void spaces is proposed, especially for treatment of tunneling and undermining Stage III/IV pressure ulcers. At the present time there are no clinically useful products that can protect transplanted cells while concurrently filling voids in tunneling/undermining wounds and promoting wound healing. A critical barrier to progress in the field is that cell injection without an appropriate scaffold leads to the cells leaving the point o injection rapidly with cells exhibiting diminished viability due to the injection process. The desin of the product facilitates incorporation into clinical practice and should enhance clinical strategies for filling wound voids and treating tunneling and undermining found in Stage III/IV pressure ulcers, which is an unmet need. The overall goal of this proposal is to commercialize an injectable system that can be used alone or in conjunction with cells to fill and treat soft tissue voids such as tunneling or undermining wounds, commonly seen in pressure ulcers. The first specific aim is manufacture, process, and sterilize the product under GMP conditions. The second aim will characterize preclinical safety of the material. In vitro cytotoxicity and mutagenicity will be determined as well as in vivo safety studies. The third specific aim will determine preclinical efficacy of the product. A rat pressure ulcer model and porcine excisional wound model, as well as a porcine tunneling wound model, will be used to determine angiogenic and wound healing potential of the product. The fourth specific aim will initiate product stability and shelf-life testing. Quality control specifications for manufacturing will be developed in addition to preliminary data collection for shelf-life testing. An injectable biomateral system which has been designed for facile delivery of cells to soft tissue defects has been developed under NIH SBIR Phase I work and is to be taken through GMP manufacturing and preclinical trials under this Phase II project to facilitate FDA submission and Phase III commercialization.

描述（由申请人提供）：压疮是影响美国数百万成年人的主要健康问题。它们可能是感染的重要部位，导致并发症，如败血症和骨髓炎，此外还造成严重的疼痛和痛苦，降低生活质量，经济负担和发病率/死亡率。随着人口老龄化，特别是糖尿病、肾脏疾病和心脏病患者，压疮的发生率很可能会继续上升。临床上公认需要改进压疮的治疗，特别是那些具有破坏和隧道空洞的压疮。在这项研究中，提出了一种可注射基质，用于安全地将自体细胞或细胞产物输送到软组织缺损或空隙中，特别是用于治疗隧道 和破坏III/IV期压疮。目前，还没有临床上有用的产品可以保护移植的细胞，同时填充隧道/破坏伤口中的空隙并促进伤口愈合。本领域进展的关键障碍是，没有适当支架的细胞注射导致细胞快速离开注射点，细胞由于注射过程而表现出降低的活力。该产品的设计有助于纳入临床实践，并应加强临床策略，以填充伤口空隙并治疗III/IV期压疮中发现的隧道和破坏，这是一个未满足的需求。该提案的总体目标是将可注射系统商业化，该系统可单独使用或与细胞结合使用，以填充和治疗软组织空隙，例如在压疮中常见的隧道或破坏伤口。第一个具体目标是在GMP条件下生产、加工和灭菌产品。第二个目的是表征材料的临床前安全性。将确定体外细胞毒性和致突变性以及体内安全性研究。第三个具体目标将决定产品的临床前有效性。将使用大鼠压疮模型和猪切除伤口模型以及猪隧道伤口模型来确定产品的血管生成和伤口愈合潜力。第四个具体目标是启动产品稳定性和保质期测试。除了有效期试验的初步数据收集外，还将制定生产质量控制规范。NIH SBIR第一阶段工作开发了一种可注射生物侧系统，旨在将细胞轻松递送至软组织缺损，并将在该第二阶段项目下通过GMP制造和临床前试验，以促进FDA提交和第三阶段商业化。