Bioprinting of MSC Exosomes for Bone Regeneration

用于骨再生的 MSC 外泌体生物打印

• 批准号: 10303337
• 负责人: CHUN-CHIEH HUANG
• 金额: $ 15.99万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303337
• 关键词: 3-Dimensional; 3D Print; Address; Adhesives; Architecture; BMP2 gene; Binding; Biochemical; Biocompatible Materials; Biological Models; Biomechanics; Bone Regeneration; Calvaria; Cell physiology; Cells; Collagen Type I; Custom; Defect; Diffusion; Encapsulated; Engineering; Evaluation; Extracellular Matrix; Extracellular Matrix Proteins; Fibronectins; Formulation; Fostering; Foundations; Future; Gel; Generations; Hardness; Histology; Hour; Human; Hydrogels; In Vitro; Infiltration; Injections; Kinetics; Knowledge; Leucine Zippers; Mediating; Mesenchymal Stem Cells; Methacrylates; Methods; Modeling; Natural regeneration; Osteogenesis; Peptides; Polymers; Porosity; Printing; Property; Rattus; Regenerative Medicine; Regulation; Research; Research Personnel; Research Proposals; Role; Selection Criteria; Standardization; Structure; System; Technology; Testing; Therapeutic; Tissue Engineering; Tissues; Tooth Diseases; Training; Vascularization; Work; base; bioprinting; bone; career; clinical translation; controlled release; craniofacial bone; craniofacial tissue; crosslink; design; engineered exosomes; exosome; experience; immunoregulation; in vivo; monomer; nanoindentation; nanotherapeutic; nanovesicle; novel; osteogenic; paracrine; post-doctoral training; programs; protein expression; regeneration function; regenerative; repaired; scaffold; stem cell exosomes; stem cell therapy; targeted delivery; three dimensional structure; tissue regeneration; tool

Abstract Mesenchymal stem cell (MSC) derived exosomes are versatile agents that possess immunomodulatory and regenerative properties and can be engineered for enhanced tissue-specific activity. To extend the advantages of such engineered exosomes, challenges to targeting, delivery and biomaterial loading need to be addressed both spatially and temporally. Addressing this knowledge gap will be a primary aspect of my independent research and this proposal is designed to provide me with the training and experience to transition into an independent investigator. I propose that 3D encapsulation and bioprinting of engineered exosomes in hydrogel carriers can address some of these challenges. On the foundations of my doctoral and postdoctoral work, I propose to engineer a tunable hydrogel system that can serve as a versatile exosome carrier and delivery platform. Two specific aims have been designed to test this hypothesis. In aim 1, I will encapsulate engineered osteoinductive exosomes in a novel hydrogel system that contains exosome binding motifs that have been identified in preliminary studies. The binding, release kinetics and functionality of the encapsulated exosomes will be quantitatively analyzed and based on application-specific (bone regeneration here) selection criteria, one candidate will be selected for aim 2. In aim 2, conditions for 3D bioprinting will be standardized for generation of photo crosslinked bioprinted 3D scaffolds with encapsulated engineered exosomes. The potency of these scaffolds to regenerate bone will be evaluated in vivo in a rat calvarial defect model. The successful completion of this project will provide a foundational knowledge for the controlled release of engineered exosomes and for their customized use in regenerative medicine using 3D bioprinting technology. This is a newly emerging field that provides an opportunity for me establish a recognized expertise and foster an academic career that focuses on regeneration using bioprinting of engineered exosomes.

抽象的 间充质干细胞（MSC）衍生的外泌体是具有免疫调节和 再生特性，可以设计用于增强组织特异性活性。扩展优势 需要解决此类工程外泌体，针对目标，交付和生物材料负荷的挑战 在空间和时间上。解决这个知识差距将是我独立的主要方面 研究和该建议旨在为我提供培训和经验，以过渡到 独立研究者。我建议水凝胶中工程外泌体的3D封装和生物打印 运营商可以解决其中一些挑战。在我的博士和博士后工作的基础上，我 提议设计一种可调水凝胶系统，该系统可以用作多功能外部载体和交付 平台。已经设计了两个具体目标来检验这一假设。在AIM 1中，我将封装 在一个新型水凝胶系统中，设计的骨诱导外泌体，该系统包含外泌体结合基序 在初步研究中已确定。封装的绑定，释放动力学和功能 外泌体将进行定量分析，并基于应用特异性（此处的骨再生）选择 标准，将选择一个候选人作为AIM 2。在AIM 2中，3D生物打印条件将标准化 带有封装的工程外泌体的照片交联的生物打印3D支架的产生。效力 在大鼠钙缺损模型中，将在体内评估这些脚手架以再生骨的再生。成功 该项目的完成将为受控释放的基础知识提供基础知识 外泌体及其在再生医学中使用3D生物打印技术的定制用途。 这是一个新兴的领域，为我提供了一个建立公认的专业知识和寄养的机会 使用工程外泌体的生物打印介绍的学术生涯，专注于再生。