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 具有再生特性，并且可以进行工程改造以增强组织特异性活性。扩大优势 对于此类工程外泌体，需要解决靶向、递送和生物材料装载方面的挑战 无论是在空间上还是在时间上。解决这一知识差距将是我独立的一个主要方面 研究和这个提案旨在为我提供培训和经验，以过渡到 独立调查员。我建议在水凝胶中对工程外泌体进行 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 建议设计一种可调节的水凝胶系统，该系统可以作为多功能的外泌体载体和递送 平台。设计了两个具体目标来检验这一假设。在目标1中，我将封装 在新型水凝胶系统中工程化骨诱导外泌体，该系统包含外泌体结合基序 已在初步研究中确定。封装的结合、释放动力学和功能 外泌体将进行定量分析并基于特定应用（此处为骨再生）选择 根据标准，将为目标 2 选择一名候选人。在目标 2 中，3D 生物打印的条件将标准化 生成带有封装的工程外泌体的光交联生物打印 3D 支架。效力 这些支架的骨再生作用将在大鼠颅骨缺损模型中进行体内评估。成功者 该项目的完成将为工程设计的受控释放提供基础知识 外泌体及其利用 3D 生物打印技术在再生医学中的定制用途。 这是一个新兴领域，为我提供了建立公认的专业知识并培养 专注于利用工程外泌体生物打印进行再生的学术生涯。