Localization of adenosine to promote fracture healing

摘要 骨折是一种非常常见的损伤，创伤导致的骨折数量急剧增加， 积极生活方式的增加。尽管骨骼具有再生能力，但骨骼损伤通常会出现延迟 治愈或不愈合。骨折的发生率和修复费用正在上升，这主要是由于老龄化造成的 人口中的一部分。对患者生活质量和经济负担的深刻负面影响 创伤或与年龄相关的脆性骨折后的骨折治疗保证了有效和 性价比高的骨折愈合佐剂，加速愈合速度，提高愈合质量。这个 拟议的研究重点是生物材料辅助局部给药腺苷促进老年人骨愈合 骨组织通过恢复内源性组织环境和修复细胞的活力。我们假设当地的 在损伤部位输送腺苷将诱导促进再生的免疫环境，并促进 通过增强成骨细胞生成和血管生成来再生老化的骨组织。这些假设 将通过以下目标进行测试。目标1将确定腺苷局部给药的效果以促进 两种损伤模型：胫骨横断性骨折和临界大小节段性骨折在老龄小鼠骨再生中的作用 股骨缺损处。目标2将确定腺苷传递在免疫调节中的作用，导致增强 骨骼再生。成功完成拟议的研究将对公共卫生产生重大影响 通过建立促进骨再生的新的治疗干预措施。

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.