纳米金-硅质体控释生长因子促进腱骨止点解剖愈合的疗效及机制研究

Anatomic healing after tendon-bone insertion injury is a difficult point in sports medicine field. Clinical surgery is to fix the injured tendon on the bone surface to form scar healing, which is easy to adhesion, poor biomechanics and high rate of re-tearing. Tissue engineering provides a new strategy for the repair of tendon-bone insertion. But how to control the release of growth factor to induce stem cell differentiation and promote anatomical healing is still a difficult problem to be solved. Our previous studies have found that high intensity focused ultrasound (HIFU) excitating silicon cerasome can be used to control release medicine, nanometer gold can promote stem cell proliferation and differentiation, 3D printing PCL scaffold can provide initial strength for tendon bone repair. We hypothesize that using the three elements together is expected to get better treatment on the injured area. This study aims to synthesize Au-HTSCs-PCL scaffold. The growth factors of BMP - 2, TGF - beta 3, HGF, bFGF and GDF – 6 are used to be controlled release. Autologous bone marrow mesenchymal stem cells were used to repair damaged tendon-bone insertion. This study aims to observe the effect of the new scaffold promoting the anatomical healing of tendon-bone insertion. To determine the effects of different controlled release time and dose of growth factor on the repair effect. To elucidate the molecular mechanism of this system in promoting the anatomic healing of tendon-bone insertion. This study will contribute to the anatomical healing of the tendon-bone insertion.

腱骨交界区损伤后解剖愈合是运动医学领域的难点，临床手术是将肌腱断端固定在骨面形成瘢痕愈合，容易粘连，生物力学较差，再撕裂率高。组织工程、干细胞结合生长因子为腱骨止点的修复提供了新策略，但如何调控生长因子的释放诱导干细胞分化，促进解剖愈合仍是待解决的难题。我们前期研究发现聚焦超声束激发硅质体可按需控释药物，纳米金可促进干细胞增殖分化，3D打印聚己内酯支架可以为腱骨修复提供初始强度，若能将三者有机结合，有望发挥各自优势，诱导腱骨愈合区种子细胞分化为肌腱-软骨-骨的解剖结构，因此本项目拟合成纳米金-硅质体-聚己内酯控释支架，用于控释BMP-2、TGF-β3、HGF、bFGF和GDF-6，结合内外源性骨髓间充质干细胞，用于修复腱骨止点的损伤，观察其促进腱骨解剖愈合的效果；确定生长因子的不同控释时间和剂量对修复效果的影响；阐明该体系促进腱骨解剖愈合的分子机制。此研究将有助于腱骨交界区解剖愈合。

腱骨交界区损伤后的解剖愈合是运动医学领域的难点，临床手术是将肌腱断端固定在骨面形成瘢痕愈合，容易粘连，生物力学较差，再撕裂率高。组织工程、干细胞结合生长因子为腱骨止点的修复提供了新策略，但如何调控生长因子的释放诱导干细胞分化，促进解剖愈合仍是待解决的难题。本研究利用聚焦超声束激发硅质体可以按需控释药物，纳米金颗粒可促进骨髓间充质干细胞增殖分化，3D打印聚己内酯支架可以为腱骨修复提供初始强度，若能将三者有机结合，有望发挥各自优势，诱导腱骨愈合区种子细胞分化为肌腱-软骨-骨的解剖结构，本项目合成了纳米金-硅质体-聚己内酯控释支架，并对其进行了材料学、细胞毒性、控释药物及生长因子的效率等表征，并在兔肩袖撕裂模型验证了其有效性，在本项目的资助下，共发表中英文论著5篇，培养硕士研究生1名（在读）、博士研究生3名（在读），培养副研究员1名。