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Transdermal Mechanical Loading for Cell Therapy-Based Bone Repair

用于基于细胞疗法的骨修复的透皮机械加载

基本信息

批准号：
9868891
负责人：
Yusuf M Khan
金额：
$ 34.1万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9868891
关键词：
3-Dimensional Acoustics Adipose tissue Alkaline Phosphatase Animal Model Belief Bone Regeneration Bone Tissue Bone Transplantation Calcium Signaling Calvaria Cell Survival Cell Therapy Cells Cellular biology Ceramics Clinical Collagen Computer Models Connecticut Data Defect Development Diagnostic radiologic examination Dinoprostone Encapsulated Engineering Environment Exposure to Fracture Gel Genes Goals Hydrogels Implant In Vitro Injections Injury Intention Laboratories Left Marrow Measurable Mechanics Methods Modeling Molecular Monitor Mus Musculoskeletal Operative Surgical Procedures Organ Transplantation Oryctolagus cuniculus Osteocalcin Osteogenesis PTGS2 gene Pathway interactions Phenotype Physiologic pulse Physiological Pliability Polymers Porifera Process Production Radiation Research Residencies Scientist Site Surgical incisions System Therapeutic Thick Time Tissue Engineering Traction Ultrasonography Universities Water Weight-Bearing state Work base bone bone healing cell behavior clinically relevant computer generated cost crosslink density design experience healing hydrogel scaffold implantation in silico in vivo mechanical load mechanical properties mineralization minimally invasive novel strategies osteopontin particle pre-clinical radiation effect repaired response sample fixation scaffold stem cells tissue repair tool

项目摘要

Cell therapy for bone repair combined with hydrogels, networks of crosslinked polymer chains with very high water content, is gaining in acceptance as a potential alternative to scaffold-based tissue engineering, especially for smaller scale defects that may be treatable through minimally invasive methods. Injecting cells into a bony defect with a small incision may be preferable to more invasive surgical procedures when clinically indicated. Once at the defect site the cells are left largely unperturbed within the hydrogel as the defect itself would require stabilization to permit healing, a requirement that goes against the therapeutic benefit of physically loading bone forming cells. It is this contradiction that has driven the work outlined in this proposal. Non-invasive, low-intensity pulsed ultrasound has been shown to be effective for transdermal treatment of fresh fractures (38% reduction in clinical and radiographic healing time) and fracture nonunions. While the mechanism through which LIPUS acts is poorly understood we have developed a highly tunable ultrasound system that demonstrates a measurable acoustic radiation force at clinically relevant ultrasound intensities and have shown this force to be capable of physically deflecting both cells and hydrogels. However, to date LIPUS-generated acoustic radiation force has not been paired with cell-loaded hydrogels for bone repair. The goal of this proposal is to combine LIPUS-generated acoustic radiation force and hydrogel-based cell therapy with the belief that both approaches together will enhance repair over either one alone. Using LIPUS- generated loading capable of imparting physical forces on cells, it is our intention to design hydrogel scaffolds that 1) are able to deliver encapsulated viable cells in vivo, 2) can be physically loaded by LIPUS generated acoustic radiation force after implantation and during the healing process and 3) can be modified to transfer varied physical forces from the hydrogel to cells such that healing would be optimized. The objectives of the present research are 1) to evaluate the effect of LIPUS-generated acoustic radiation force on cells embedded in hydrogels with increasing crosslinking densities, 2) to evaluate the effect of radiation force on cells encapsulated in collagen hydrogels of varying mechanical properties to determine the relationship between applied force and hydrogel stiffness on cell behavior, and 3) to use radiation force applied to hydrogels that have been loaded with cells and implanted in bone defect models. Implanted hydrogels containing cells will be loaded transdermally using acoustic radiation force. It is anticipated that the parameters defined in the in vitro studies will result in enhanced in vivo defect healing in hydrogels under acoustic radiation force when compared to either parameter alone.

骨修复细胞疗法与水凝胶结合，具有很高的交联聚合物链网络