Localization of adenosine to promote fracture healing

腺苷定位促进骨折愈合

• 批准号: 10461465
• 负责人: Shyni Varghese
• 金额: $ 50.25万
• 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/10461465
• 关键词: ADORA2A gene; Acids; Address; Adenosine; Adjuvant; Age; Aging; Animals; BMP2 gene; Behavior; Biocompatible Materials; Blood Circulation; Bone Diseases; Bone Injury; Bone Regeneration; Bone Tissue; Bone Transplantation; Bone callus; CD8-Positive T-Lymphocytes; Cells; Clinical; Cyclic AMP; Defect; Development; Dose; Economic Burden; Elderly; Environment; Flow Cytometry; Fracture; Functional disorder; Gait; Gene Expression; Half-Life; Histologic; Hyaluronic Acid; Immune; Immune response; Impaired healing; Implant; In Situ; Injectable; Injury; Knock-out; Literature; Matrix Metalloproteinases; Mechanics; Modeling; Mus; Natural regeneration; Nature; Operative Surgical Procedures; Osteogenesis; Osteoporosis; Patients; Plasma; Play; Population; Prevalence; Proteins; Public Health; Purinergic P1 Receptors; Quality of life; Receptor Signaling; Regulatory T-Lymphocyte; Research; Role; Signal Transduction; Site; T-Lymphocyte; Testing; Therapeutic; Tibial Fractures; Tissues; Trauma; Vascularization; Wild Type Mouse; active lifestyle; age related; aged; angiogenesis; base; bone; bone aging; bone fracture repair; bone healing; bone health; bone quality; cost; cost effective; crosslink; cytokine; extracellular; fragility fracture; healing; immunoregulation; improved; juvenile animal; laser capture microdissection; longitudinal analysis; macrophage; 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.

抽象的 骨折是非常常见的损伤，由于创伤引起的骨折的急剧增加 积极生活方式的增长。尽管骨骼具有再生能力，但骨损伤经常遭受延迟 治愈或非工会。由于老化，骨折的患病率和维修成本在上升 人口。对患者生活质量和经济燃烧的深远影响 创伤或与年龄相关的骨折后的骨折治疗值得开发有效和 具有成本效益的断裂式调节器，以加速愈合率并提高愈合质量。这 拟议的研究重点是生物材料辅助腺苷的局部递送，以促进老化的骨骼愈合 通过恢复内源性组织环境和修复细胞来使骨正时。我们假设本地 在伤害部位输送腺苷将诱发促增再生效的免疫环境并促进 通过增强的成骨细胞生成和血管生成来使衰老骨组织的再生。这些假设 将通过以下目标进行测试。 AIM 1将确定腺苷局部递送以促进的影响 使用两种损伤模型：横向胫骨骨折和临界大小的分段，使用两种损伤模型 股骨缺陷。 AIM 2将确定腺苷递送在免疫调节中的作用，从而增强 骨再生。成功完成拟议的研究将对公共卫生产生重大影响 通过建立新的治疗干预措施来促进骨骼再生。