3D Encapsulation, Bioprinting and Controlled Delivery of Functionally Engineered EVs (FEEs)

功能工程电动汽车 (FEE) 的 3D 封装、生物打印和受控交付

• 批准号: 10633258
• 负责人: LYNDON F COOPER
• 金额: $ 47.41万
• 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: 2021-06-18 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633258
• 关键词: 3-Dimensional; 3D Print; Activities of Daily Living; Address; Alginates; Anti-Inflammatory Agents; Architecture; Area; BMP2 gene; Binding; Biological Assay; Biological Models; Biology; Calvaria; Cartilage; Cells; Chronic; Complex; Cues; Defect; Dental; Development; Disease; Dose; Encapsulated; Engineering; Equilibrium; Event; Extracellular Matrix; Genes; Goals; Growth Factor; Health; Histology; Hybrids; Hydrogels; Immunology; Impairment; Individual; Inflammasome; Inflammation; Inflammatory; Injury; Ink; Kinetics; Knowledge; Laboratories; MADH7 gene; MMP2 gene; Macrophage; Measurement; Mediator; Mesenchymal Stem Cells; Modeling; Muscle; Musculoskeletal; Musculoskeletal System; Natural regeneration; Nerve; Pathway interactions; Peptides; Phase; Play; Polymers; Printing; Process; Production; Property; Rattus; Regenerative Medicine; Regenerative pathway; Reporter; Role; Signal Transduction; Site; Specific qualifier value; Structure; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Work; bioprinting; body system; clinical translation; controlled release; craniofacial; craniofacial tissue; crosslink; cytokine; extracellular vesicles; immunoregulation; improved; in vivo; monomer; novel strategies; paracrine; precision medicine; prevent; protein expression; recruit; regenerative; repaired; scaffold; spatiotemporal; stem cell exosomes; stem cell therapy; stem cells; technology platform; tissue injury; tissue regeneration; tissue repair; tool

Summary: Tissue repair is a complex process that involves a delicate temporal balance between inflammatory and regenerative mechanisms. In health, initial inflammatory events are replaced by regenerative processes in a coordinated manner. This sequence is disrupted in diseased states and complex injuries. The goal of regenerative medicine is to reestablish this balance by preventing chronic/aberrant inflammation and promoting repair and regeneration in a tissue-specific manner. While stem cell and growth factor therapies have been explored for this purpose traditionally, recent studies highlight the immunomodulatory and protective functions of mesenchymal stem cell derived extracellular vesicles (MSC EVs). Although MSC EVs possess versatile properties, to engage tissue-specific pathways and fit the goals of precision medicine with translational relevance, MSC EVs have to be engineered for enhanced pathway-specific functionality and delivered on site in a spatially and temporally controlled manner. In this proposal, leveraging our preliminary results and our expertise in EV biology, immunology and bone biology, we hypothesize that: Spatiotemporal control of immunomodulatory and regenerative pathways can be achieved by selective incorporation of Functionally Engineered EVs (FEEs)in 3D printed scaffolds. Using bone regeneration as a model system, we will test this hypothesis in three specific aims. In aim 1, we will generate functionally engineered EVs (FEEs) that target specific osteoinductive and immunomodulatory pathways. In aim 2, we will develop a photocrosslinkable alginate-based delivery system with EV carrier and release motifs for spatial localization and temporally controlled delivery of the FEEs developed in aim 1. In aim 3, we will utilize 3D printing technology to print defined structures encapsulating the FEEs for spatially and temporally controlled biphasic delivery in vivo. This system will be tested in a rat calvarial defect model. From the proposed studies, we will develop a platform technology that can impact the field of regenerative medicine beyond the craniofacial and musculoskeletal systems.

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