Localization of adenosine to promote fracture healing

腺苷定位促进骨折愈合

• 批准号: 10700832
• 负责人: Shyni Varghese
• 金额: $ 51.85万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700832
• 关键词: ADORA2A gene; Acceleration; Acids; Address; Adenosine; Adjuvant; Age; Aging; Animals; BMP2 gene; Behavior; Biocompatible Materials; Bone Diseases; Bone Injury; Bone Regeneration; Bone Tissue; Bone Transplantation; Bone callus; CD8-Positive T-Lymphocytes; Cells; Circulation; Clinical; Cyclic AMP; Defect; Development; Dose; Economic Burden; Elderly; Environment; Femur; Flow Cytometry; Fracture; Functional disorder; Gait; Gel; Gene Expression; Half-Life; Histologic; Hyaluronic Acid; Immune; Immune response; Impaired healing; Implant; In Situ; Injectable; Injury; Knock-out; Literature; Macrophage; Matrix Metalloproteinases; Mechanics; Modeling; Mus; Natural regeneration; Nature; Osteogenesis; Osteoporosis; Patients; Phosphorylation; Plasma; Play; Population; Prevalence; Public Health; Purinergic P1 Receptors; Quality of life; Receptor Signaling; Regulatory T-Lymphocyte; Rejuvenation; Research; Role; Signal Transduction; Site; Sorting; T-Lymphocyte; Testing; Therapeutic; Tibial Fractures; Tissues; Trauma; Vascularization; Wild Type Mouse; active lifestyle; age related; aged; angiogenesis; bone; bone aging; bone fracture repair; bone healing; bone health; bone quality; cost; cost effective; crosslink; cytokine; efficacy evaluation; extracellular; fragility fracture; healing; immunoregulation; improved; juvenile animal; laser capture microdissection; longitudinal analysis; neutrophil; novel therapeutic intervention; older patient; peripheral blood; regenerative; repaired; scaffold; sex; single-cell RNA sequencing; spatiotemporal; success; tissue regeneration; tissue repair

ABSTRACT Bone fracture is a very common injury, and there has been a dramatic increase in trauma-induced fractures with the increase in active lifestyle. Despite the regenerative ability of bone, bone injuries often suffer from delayed healing or non-unions. The prevalence of bone fracture and the cost of repair is on the rise primarily due to aging of the population. The profound negative impact on the patient’s quality of life and the economic burden of fracture treatment following trauma or age-related fragility fractures warrants the development of efficient and cost-effective fracture-healing adjuvants to accelerate the healing rate and improve the quality of healing. The proposed research focuses on biomaterial-assisted local delivery of adenosine to promote bone healing of aged bone tissues by rejuvenating the endogenous tissue environment and reparative cells. We hypothesize that local delivery of adenosine at the injury site will induce a pro-regenerative immune environment and promote regeneration of aging bone tissues through enhanced osteoblastogenesis and angiogenesis. These hypotheses will be tested through the following aims. Aim 1 will determine the effect of local delivery of adenosine to promote bone regeneration in aged mice by using two injury models: transverse tibial fracture and critical-sized segmental femoral defect. Aim 2 will determine the role of adenosine delivery on immunomodulation leading to enhanced bone regeneration. Successful completion of the proposed studies will have a significant impact in public health by establishing a new therapeutic intervention for promoting bone regeneration.

摘要