Clickable Microgel Scaffolds for MSC Expansion and Delivery

用于 MSC 扩展和交付的可点击微凝胶支架

• 批准号: 10584600
• 负责人: KRISTI S. ANSETH
• 金额: $ 53.4万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-05 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584600
• 关键词: Address; Attention; Biocompatible Materials; Bone Marrow; Bone Regeneration; Calvaria; Cell Communication; Cell Count; Cell Separation; Cells; Chemistry; Clinical; Clinical Trials; Coculture Techniques; Complex; Confocal Microscopy; Craniofacial Abnormalities; Cues; Defect; Disease; Dose; Engineering; Engraftment; Enzyme-Linked Immunosorbent Assay; Epigenetic Process; Exposure to; Failure; Fibroblast Growth Factor; Formulation; Fracture; Functional disorder; Gel; Goals; Histologic; Homeostasis; Hour; Human; Hydrogels; Image; Implant; In Situ; In Vitro; Inflammatory; Inflammatory Response; Injections; Luciferases; Macrophage; Measures; Mechanics; Mesenchymal Stem Cells; Methods; Modeling; Monitor; Musculoskeletal; Operative Surgical Procedures; Osteogenesis; Osteoporosis; Osteoporotic; Outcome; Ovariectomy; Patients; Peptides; Phenotype; Play; Porosity; Process; Proliferating; Property; Public Health; Rattus; Recording of previous events; Regenerative capacity; Research; Role; Signal Transduction; Site; Structure; System; TNF gene; Testing; Therapeutic; Time; Tissues; Transplantation; Traumatic injury; bone; bone healing; bone quality; cell motility; clinically relevant; congenital anomaly; craniofacial; craniofacial bone; craniofacial complex; craniofacial repair; cytokine; economic impact; healing; improved; in vivo; in vivo evaluation; in vivo imaging system; in vivo regeneration; innovation; mechanical signal; mechanotransduction; microCT; osteogenic; osteoporotic bone; regeneration function; regeneration potential; regenerative; repaired; reparative capacity; scaffold; self-renewal; socioeconomics; stem cell delivery; stem cell expansion; stem cell population; stem cell proliferation; stem cell survival; stem cell therapy; stem cells

PROJECT SUMMARY Repair of craniofacial bone defects is an important clinical problem with significant socioeconomic impact. Bone that is traumatically injured or diseased often requires surgical repair, but 5-10% of bone fractures fail to heal and failure rates can be even higher when the patient's bone quality is compromised (e.g., osteoporotic). In these cases, stem cell-based therapies have received increasing attention as a method to improve the healing of complex craniofacial defects. The proposed research focuses on mesenchymal stem cell (MSC) therapies because of their extensive use in clinical trials, as well as the major role that MSCs play in musculoskeletal tissue homeostasis and the pathophysiology of osteoporosis. However, in vitro expansion of MSCs to therapeutically relevant numbers reduces their regenerative capacity, and afterwards, direct injection of MSCs alone often leads to low survival. The proposed research addresses this important clinical problem through an innovative materials-based strategy, namely the synthesis and assembly of tunable microgel scaffolds for MSC expansion and delivery. Using efficient “click” chemistries and by developing photoresponsive materials, we hypothesize that scaffolds can be tuned to: i) prolong the self-renewing and regenerative capacity of MSCs during in vitro expansion and ii) promote the survival and regenerative functions of delivered MSCs that will improve healing of both healthy and osteoporotic bone. Specifically, we propose to: Aim 1. Develop a hydrogel culture system for MSC expansion and quantify the effects of mechanical cues and passaging history on MSC proliferation, multipotency, secretory properties, and epigenetic landscape; Aim 2. Process the hydrogel materials into modular microgel units for MSC delivery and tailor their properties to promote MSC survival, retention and regenerative potential; and Aim 3. Test the influence of MSC expansion conditions and modular microgel delivery systems on MSC survival and bone regeneration in vivo. If successful, this project will have an important impact on public health by providing a powerful new platform for the expansion and site specific delivery of MSCs. Given the versatility of the approach, which can be applied to numerous cell delivery systems, the results will have broader implications that can extend beyond bone regeneration.

项目总结

项目成果

Photo-click living strategy for controlled, reversible exchange of biochemical ligands.

• DOI: 10.1002/adma.201304847
• 发表时间: 2014-04-23
• 期刊: Advanced materials (Deerfield Beach, Fla.)
• 作者: Gandavarapu NR;Azagarsamy MA;Anseth KS
• 通讯作者: Anseth KS

Covalently tethered transforming growth factor beta in PEG hydrogels promotes chondrogenic differentiation of encapsulated human mesenchymal stem cells.

• DOI: 10.1007/s13346-012-0090-2
• 发表时间: 2012-10
• 期刊: DRUG DELIVERY AND TRANSLATIONAL RESEARCH
• 影响因子: 5.4
• 作者: McCall, Joshua D.;Luoma, Jacob E.;Anseth, Kristi S.
• 通讯作者: Anseth, Kristi S.

Hydrogels with Reversible Mechanics to Probe Dynamic Cell Microenvironments.

• DOI: 10.1002/anie.201705684
• 发表时间: 2017-09-25
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Rosales AM;Vega SL;DelRio FW;Burdick JA;Anseth KS
• 通讯作者: Anseth KS

Extracellular matrix protein adsorption to phosphate-functionalized gels from serum promotes osteogenic differentiation of human mesenchymal stem cells.

• DOI: 10.1016/j.actbio.2012.09.007
• 发表时间: 2013-01
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Gandavarapu, Navakanth R.;Mariner, Peter D.;Schwartz, Michael P.;Anseth, Kristi S.
• 通讯作者: Anseth, Kristi S.

Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction.

• DOI: 10.1021/ma200202w
• 发表时间: 2011-04-26
• 期刊: Macromolecules
• 影响因子: 5.5
• 作者: Fairbanks BD;Singh SP;Bowman CN;Anseth KS
• 通讯作者: Anseth KS