Microengineering vascularized and innervated bone-like scaffolds as an alternative to autologous bone grafts

微工程血管化和神经支配的骨样支架作为自体骨移植的替代品

• 批准号: 10614543
• 负责人: Luiz Eduardo Bertassoni
• 金额: $ 61.24万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614543
• 关键词: 3-Dimensional; 3D Print; Address; Autologous; Autologous Transplantation; Biocompatible Materials; Biological; Biological Models; Biomanufacturing; Biomimetics; Blood Vessels; Blood capillaries; Blood flow; Bone Matrix; Bone Regeneration; Bone Substitutes; Bone Tissue; Bone Transplantation; Bone structure; Calvaria; Cells; Cementation; Characteristics; Clinic; Clinical; Communication; Defect; Development; Engineering; Excision; Failure; Future; Gel; Harvest; Hospital Costs; Hydrogels; Impairment; Implant; In Vitro; Injectable; Malignant Neoplasms; Mesenchymal Stem Cells; Methods; Microfluidic Microchips; Microfluidics; Minerals; Morbidity - disease rate; Nanostructures; Natural regeneration; Nerve Fibers; Nervous System; Neurons; Operative Surgical Procedures; Oral; Osteogenesis; Outcome; Paracrine Communication; Pericytes; Phenotype; Physiologic calcification; Play; Procedures; Process; Property; Regenerative capacity; Series; Site; Structure; System; Testing; Time; Tissue Donors; Tissue Engineering; Tissue constructs; Tissues; Trauma; Vascular blood supply; Vascularization; Work; biomineralization; bone; bone engineering; bone marrow mesenchymal stem cell; bone repair; bone scaffold; calcification; clinical application; cost; design; endothelial stem cell; extracellular; human stem cells; implantation; improved; in vitro regeneration; in vivo; in vivo regeneration; innovation; long bone; manufacture; manufacturing process; mineralization; nano; nanoengineering; nanoscale; nerve stem cell; nerve supply; novel; osteogenic; osteoprogenitor cell; physical property; regeneration potential; regenerative; regenerative approach; response; scaffold; scale up; skeletal; stem cell differentiation; stem cells; success; tool; virtual

PROJECT SUMMARY A wide range of skeletal conditions require assisted bone repair, including trauma, cancer resections, and bone augmentation for oral implant therapy. Current methods to treat these conditions rely on procedures to harvest and implant bone autografts, which are costly, invasive and difficult to scale up. The other alternatives are synthetic bone replacement materials, which show high failure rates and fail to mimic the native bone structure, composition and osteogenic properties. Stem cell-based tissue engineering has long been proposed as a promising alternative for the repair of bone defects. However, treating large bony structures remains problematic. It is generally believed that scaffold materials that closely approximate the characteristics of native bone represent improved materials for bone regeneration. However, the development of in-vitro scaffolds mimicking the highly vascularized, innervated, and mineralized cell-rich bone matrix down to the nanoscale has remained elusive to date. Here, we will develop a new bone scaffold biomanufacturing process where osteoprogenitor cells are three-dimensionally embedded in controlled nano-mineralized, pre-vascularized and innervated bone-like injectable microgels, thus mimicking the mineralized nanostructure, cellular and extracellular microenvironment of native bone. (aim 1) We will determine the mechanistic characteristics enabling the differentiation of hMSCs into osteogenic phenotypes as influenced by bone-like microenvironments, and engineer cell-laden mineralized injectable microgels that approximate the regenerative potential of autologous bone grafts. We will then adapt this strategy to engineer (aim 2) pericyte-supported vascular capillaries and (aim 3) neuronal networks, that are embedded in nanoscale mineralized hydrogels, to determine the mechanisms that enable vasculature and innervation enhancement of osteogenesis in-vitro and regeneration in-vivo. We argue that this multi-pronged strategy will enable the engineering of highly innovative bone scaffold materials and in-vitro bone model systems that will share great nanostructural and physical similarities to native bone. Ultimately, this will lead to biomaterials that closely approximate the regenerative potential of autologous bone in the clinic.

项目总结

项目成果

Matrix stiffness regulates lipid nanoparticle-mRNA delivery in cell-laden hydrogels.

基质刚度调节脂质纳米粒子-mRNA在充满细胞的水凝胶中的传递。

• DOI: 10.1016/j.nano.2022.102550
• 发表时间: 2022-06
• 期刊: NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
• 影响因子: 5.4
• 作者: Athirasala, Avathamsa;Patel, Siddharth;Menezes, Paula P.;Kim, Jeonghwan;Tahayeri, Anthony;Sahay, Gaurav;Bertassoni, Luiz E.
• 通讯作者: Bertassoni, Luiz E.

Engineering of an Osteoinductive and Growth Factor-Free Injectable Bone-Like Microgel for Bone Regeneration.

用于骨再生的骨诱导和无生长因子可注射骨样微凝胶的工程。

• DOI: 10.1002/adhm.202200976
• 发表时间: 2023
• 期刊: Advanced healthcare materials
• 影响因子: 10
• 作者: Subbiah,Ramesh;Lin,EdithY;Athirasala,Avathamsa;Romanowicz,GenevieveE;Lin,AngelaSP;Califano,JosephV;Guldberg,RobertE;Bertassoni,LuizE
• 通讯作者: Bertassoni,LuizE

Correction to: 3D-printed microgels supplemented with dentin matrix molecules as a novel biomaterial for direct pulp capping.

更正：添加牙本质基质分子的 3D 打印微凝胶作为直接盖髓的新型生物材料。

• DOI: 10.1007/s00784-022-04772-8
• 发表时间: 2023
• 期刊: Clinical oral investigations
• 影响因子: 3.4
• 作者: Cunha,Diana;Souza,Nayara;Moreira,Manuela;Rodrigues,Nara;Silva,Paulo;Franca,Cristiane;Horsophonphong,Sivaporn;Sercia,Ashley;Subbiah,Ramesh;Tahayeri,Anthony;Ferracane,Jack;Yelick,Pamela;Saboia,Vicente;Bertassoni,Luiz
• 通讯作者: Bertassoni,Luiz

Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions.

• DOI: 10.3389/fimmu.2023.1162905
• 发表时间: 2023
• 期刊: Frontiers in immunology
• 影响因子: 7.3

In vitro development and optimization of cell-laden injectable bioprinted gelatin methacryloyl (GelMA) microgels mineralized on the nanoscale.

• DOI: 10.1016/j.bioadv.2024.213805
• 发表时间: 2024-03
• 期刊: Biomaterials advances
• 作者: Mauricio Goncalves da Costa Sousa;G. de Souza Balbinot;Ramesh Subbiah;Rahul M. Visalakshan;A. Tahayeri