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Clickable Extracellular Vesicles to Silk-Based Biomaterials for Regenerative Medicine

用于再生医学的可点击细胞外囊泡到丝基生物材料

基本信息

批准号：
10642420
负责人：
PHIL GORDON CAMPBELL
金额：
$ 73.45万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10642420
关键词：
Azides Biocompatible Materials Cell-Matrix Junction Cells Chemistry Clinical Development Dose Endothelial Cells Engraftment Evaluation Exposure to Extracellular Matrix FDA approved Fibroblasts Fibroins Film Focus Groups Homeostasis Human Immobilization In Vitro Industrialization Infiltration Legal patent Ligand Binding Logistics Mesenchymal Stem Cells Mission Modeling Modification Multipotent Stem Cells Mus Outcome Phenotype Process Production Proliferating Quality Control Rattus Reactive Oxygen Species Regenerative Medicine Research Research Personnel Role Signal Transduction Silk Smooth Muscle Myocytes Surface Techniques Technology Testing Therapeutic Therapeutic Effect Time Tissue Engineering Tissues Tube Vascular Graft Work Wound models angiogenesis biological systems cell behavior chronic wound clinical translation commercialization covalent bond culture plates diabetic extracellular vesicles immunoregulation implantation improved industry partner innovation insight interest large scale production migration monocyte multidisciplinary nanosized next generation novel physical property regeneration potential regenerative scale up self-renewal tissue regeneration tissue repair tumor vascular tissue engineering wound wound bed wound healing

项目摘要

PROJECT SUMMARY Successful regenerative medicine approaches require harnessing the appropriate cell signals at the right time to direct host tissue functions. These signals are often informed by the natural regenerative processes controlled during development and homeostasis by mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs), which allow a cell-based yet cell-free approach for downstream regenerative technologies. This multidisciplinary, MPI proposal brings together a team of two senior investigators leading regenerative medicine-focused group with complementary strengths, co-investigators with critical roles, and industrial partner RoosterBio, Inc. Together, we will create and test an innovative enabling technology to stably incorporate EVs to a biomaterial intended for tissue engineering and regenerative medicine applications. Specifically, we will use a novel azide-based click chemistry technique to controllably immobilize EVs to silk fibroin as a demonstrative application, but immobilization can also be done on other biomaterials, substrates, or surfaces, or even tissues. We chose silk as our biomaterial in this application given its FDA-approved status and wide use. We hypothesize that “azide-clickable" MSC-derived EVs (which we will refer to simply as “Az-EVs”) will have more stable immobilization to silk fibroin biomaterials than unmodified EVs, and this will result in higher regenerative potency. To test this hypothesis and provide proof-of-concept applications, we will pursue four specific aims: Aim 1 - Demonstrate and validate Az-EV immobilization to silk fibroin-based materials; Aim 2 - Demonstrate the MSC-mimicking effects of Az-EVs immobilized to silk in vitro; Aim 3 - Demonstrate the regenerative effects of Az-EVs in a mouse chronic wound healing model; Aim 4 - Demonstrate the regenerative effects of Az-EVs in a rat tissue engineered vascular graft model. Partner RoosterBio, Inc. will “industrialize” (scale-up) the production of MSC-derived Az-EVs for commercialization to make available to other researchers and clinicians. This research will provide insight to the efficacy of this novel selective EV immobilization technology to efficiently direct EV delivery within a biological system of interest. Our proof-of-concept studies will demonstrate how utilization of this regenerative technology can aid in treating chronic wounds and enabling TEVGs with improved patency rates.

项目总结