权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Heat-Treated Porous Fluorapatite Scaffolds with Adipose Derived Stem Cells for Bone Regeneration

热处理多孔氟磷灰石支架与脂肪干细胞用于骨再生

基本信息

批准号：
10557062
负责人：
Jayant Prasad Agarwal
金额：
--
依托单位：
VA SALT LAKE CITY HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10557062
关键词：
3-Dimensional Adhesions Adipose tissue Adopted Age Alkaline Phosphatase Allografting Analysis of Variance Animals Aspirate substance Autologous Transplantation Autopsy Biocompatible Materials Biological Biological Assay Biomedical Engineering Blood Vessels Bone Morphogenetic Proteins Bone Regeneration Bone Substitutes Bone Tissue Bone Transplantation Cadaver Caliber Cell Fraction Cell Survival Cells Clinical Collagen Compressive Strength Confocal Microscopy Custom Data Defect Dental Care Dental Pulp Dentistry Disease Engineering Euthanasia Extracellular Matrix Proteins Fatty acid glycerol esters Femur Freezing Gel Gene Expression Gold Growth Factor Harvest Health Histology Hydroxyapatites In Vitro Individual Infection Intravenous Knee Lateral Left Length Limb structure Malignant Neoplasms Mechanics Military Personnel Modeling Monitor Natural regeneration Operative Surgical Procedures Orthopedics Osteoblasts Osteocalcin Oxytetracycline Patients Physiologic calcification Plastic Surgical Procedures Population Porosity Process Property Quality of life Rattus Reporting Research Personnel Risk Scanning Scanning Electron Microscopy Shapes Signal Transduction Site Source Surface Techniques Temperature Testing Time Tissues Titanium Trauma Vascular blood supply Veterans Weight-Bearing state Wistar Rats X-Ray Computed Tomography adverse outcome base battlefield injury biomaterial compatibility bone bone loss bone repair bone scaffold cell type clinical material combat comorbidity conventional therapy density design efficacy testing fluorapatite improved in vitro testing in vivo mechanical properties microCT military veteran mineralization novel osteogenic osteopontin overexpression physical property protein expression regeneration potential repaired scaffold skeletal standard care stem cell differentiation stem cells substantia spongiosa success tissue regeneration wound

项目摘要

Segmental bone loss due to high-energy trauma, such as battlefield injuries, are limb-threatening conditions, but there are limited treatment options available. Conventional treatments include bone grafts, vascularized bone transplant, and allografts. Bone repair using vascularized autografts is arguably the best current approach, because the repair process will proceed with the patient’s own tissue and blood supply, which can be harvested at the time of surgery. This eliminates many adverse outcomes associated with allografts and bioengineered bone substitutes. However, donor autograft sites are limited, and thus, its supply cannot meet the demand. It also requires a second surgical site, which could result in further comorbidities. Decellularized allografts harvested from cadaveric sources have the advantage of being osteoconductive. However, they are associated with risk of host rejection and accelerated graft resorption. Current bioengineered grafts focus on providing the necessary matrix to support bone regeneration by providing biocompatible, bioresorbable, and porous scaffolds made from materials such as hydroxyapatite, collagen and synthetic materials. It is now clear that bioengineered grafts also need a reliable source of osteogenic progenitor cells as well as osteogenic signals to be effective bone substitutes. To improve upon these initial designs, researchers made new scaffolds that integrated extracellular matrix proteins or growth factors, typically bone morphogenetic proteins (BMPs), but with limited success. Often the strength of the scaffolding remains the main hurdle for weight-bearing after surgery. To this end, we fabricated a fully interconnecting porous fluorapatite (FA) scaffold by adopting a “gel-casting” process, and then heat-treating to optimize the mechanical strength. As these surfaces are osteogenic, they also enhance osteoblast adhesion, proliferation, and differentiation. Interestingly, these scaffolds also possess the ability to differentiate stem cells (adipose derive stem cells) to an osteogenic lineage without any osteogenic signals (e.g. exogenous BMPs). More notably, the “gel-casting” technique allows custom fabrication of desired shapes and sizes of rigid scaffoldings to fit individual defects. Thus, we hypothesize that FA scaffoldings seeded with a patient’s own adipose tissue-derived stromal vascular fraction (SVF) stem cells will have the ability to regenerate osseous tissue. This hypothesis will be tested in three aims. Specific Aim 1 will investigate the mechanical, physical, and degradation properties of the porous fluorapatite scaffolds, which will be generated by the gel-casting technique. Specific Aim 2 will quantify the in vitro adhesion and differentiation properties of the SVF cells on porous FA surfaces. Specific Aim 3 will investigate the osteogenic potential of the FA scaffolding with and without SVF in a rat femoral condyle model. It is expected that such combination treatment of SVF and FA scaffolds will provide a potential source of “off-the-shelf” scaffolding materials for clinical bone repair and regeneration and improve the health and quality of life for a number of military personnel, veterans, and civilians. ! !

高能创伤造成的节段性骨质流失，比如战场创伤，对肢体是有威胁的，但是