Fibrinogen coated albumin spheres to accelerate bone healing in older adults.

纤维蛋白原涂层白蛋白球可加速老年人的骨骼愈合。

• 批准号: 10371263
• 负责人: Richard Yen
• 金额: $ 24.66万
• 依托单位: FIBROPLATE, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371263
• 关键词: Adverse effects; Adverse event; Age; Albumins; Animals; Anti-Inflammatory Agents; Biological Products; Biological Response Modifier Therapy; Biomechanics; Blood; Blood Platelets; Bone Regeneration; Bone Tissue; Bone callus; CD34 gene; Caring; Cells; Clinical; Clinical Management; Clinical Trials; Cognitive; Data; Development; Dose; ENG gene; Early Mobilizations; Economics; Elderly; Endothelium; Equilibrium; Evaluation; Femoral Fractures; Femur; Fibrinogen; Formulation; Fracture; Fracture Healing; Goals; Health; Healthcare; Heart failure; Hematopoietic Stem Cell Mobilization; Hemorrhage; Hemostatic Agents; Hip Fractures; Histologic; Immune; Impaired healing; Incidence; Infection; Inflammatory; Injectable; Injury; Intellectual Property; Intravenous; Knowledge; Legal patent; Life; Measures; Mental Depression; Mesenchymal Stem Cells; Metabolism; Modeling; Monitor; Morbidity - disease rate; Nanosphere; Necrosis; Operative Surgical Procedures; Osteopenia; Osteoporosis; Outcome; PECAM1 gene; Patients; Pharmacological Treatment; Phase; Population; Pre-Clinical Model; Process; Property; Public Health; Rattus; Recovery; Regulation; Research; Risk; Roentgen Rays; Saline; Signal Transduction; Site; Small Business Innovation Research Grant; Structure; Suspensions; Testing; Time; Tissues; Torsion; Toxic effect; Trauma; VWF gene; Visual impairment; Weight; Work; X-Ray Computed Tomography; age related; aged; base; bone; bone fragility; bone healing; bone strength; cadherin 5; chronic wound; cost; cytokine; dietary supplements; disability; economic impact; effective therapy; endothelial stem cell; falls; fragility fracture; functional independence; healing; healthy aging; high risk; improved; mortality; mortality risk; nanoscale; novel strategies; novel therapeutics; older patient; pre-clinical; preclinical study; progenitor; repaired; socioeconomics; soft tissue; stem cells; wound; wound healing

PROJECT SUMMARY Elderly people are at great risk for bone fracture and they are more likely to suffer complications during fracture healing. An inefficient healing process exposes the elderly to higher rates of delayed healing or nonunions. The slow recovery after geriatric fractures dramatically increases risks of degenerative decline, morbidity, and mortality with a negative socio-economic impact. Available solutions to facilitate bone regeneration are either invasive or show adverse events in aged people. Intravenous injectable Fibrinogen-coated Albumin nano-Spheres (FAS) are nanometer-sized spheres with a unique multivalent potential to accelerate chronic wound healing in multiple soft tissues. FAS has been shown to promote mobilization of progenitor cells of various lineages including Endothelial Progenitor Cells (EPCs), a cell population responsible also for bone regeneration, and to counteract inflammatory states. Studies conducted on young rats showed that FAS administered after fracture promotes the superior strength and structure of the healed bone. By taking advantage of this knowledge, Fibroplate Inc. proposes to investigate the efficacy of Fibrinoplate-S (FPS), a FAS formulation, as a biological agent to accelerate the healing of fractured bones in geriatric patients. If successful, FPS could represent a new therapeutic that can improve the health and functional independence of older adults. In this SBIR Phase I project Fibroplate aims to accomplish two objectives: 1) Demonstrate the efficacy of FPS in bone fracture healing in aged pre-clinical rat models. FPS will be administered after femur surgical fracture to assess the bone healing process through quantitative computed tomography, histological analysis, and biomechanical evaluation of bone strength. 2) Confirm the mobilization of stem cells induced by FPS to delve deeper into the mechanism of action. This work will be preparatory of a Phase II project where an extensive IND-enabling preclinical study will be performed to establish metabolism, dose, and toxicity, together with a long-term assessment of the bone healing process. The final goal is to obtain FDA approval of FPS as a new healing agent in age-related bone fractures. By offering an effective treatment for frail patients, Fibroplate is expected to improve and promote healthy aging.

项目概要 老年人骨折的风险很大，骨折期间更容易出现并发症 康复。低效的愈合过程使老年人面临更高的延迟愈合或骨不连发生率。这 老年骨折后恢复缓慢会显着增加退行性衰退、发病率和 死亡率带来负面的社会经济影响。促进骨再生的可用解决方案是 对老年人有侵入性或表现出不良事件。静脉注射纤维蛋白原包被白蛋白 纳米球 (FAS) 是纳米尺寸的球体，具有独特的多价潜力，可加速慢性 多个软组织的伤口愈合。 FAS 已被证明可以促进各种祖细胞的动员 谱系包括内皮祖细胞（EPC），也是负责骨再生的细胞群， 并对抗炎症状态。对幼鼠进行的研究表明，FAS 给药后 骨折可促进愈合骨骼的优异强度和结构。通过利用这些知识， Fibroplate Inc. 提议研究 Fibrinoplate-S (FPS)（一种 FAS 制剂）作为生物制剂的功效 加速老年患者骨折愈合的药物。如果成功，FPS 可能代表一种新的 可以改善老年人的健康和功能独立性的治疗方法。在这个SBIR第一期项目中 Fibroplate 旨在实现两个目标：1) 证明 FPS 在骨折愈合中的功效 老年临床前大鼠模型。股骨手术骨折后将进行 FPS 以评估骨愈合情况 通过定量计算机断层扫描、组织学分析和骨生物力学评估过程 力量。 2) 确认FPS诱导干细胞动员，深入探究其作用机制。 这项工作将为第二阶段项目做准备，该项目将进行广泛的 IND 支持的临床前研究 进行以确定代谢、剂量和毒性，以及骨愈合的长期评估 过程。最终目标是获得 FDA 批准 FPS 作为年龄相关性骨折的新型愈合剂。 通过为体弱患者提供有效的治疗，Fibroplate 有望改善和促进健康老龄化。