掺镁聚乳酸微球在大鼠肩袖损伤外科修复中的作用  

Role of magnesium-doped polylactic acid microspheres in surgical repair of rat rotator cuff injuries

作　　者：袁梓洋 康育豪 李亚民 赵金忠[1] YUAN Ziyang;KANG Yuhao;LI Yamin;ZHAO Jinzhong(Department of Sports Medicine,Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200233,China)

机构地区：[1]上海交通大学医学院附属第六人民医院运动医学科,200233

出　　处：《国际骨科学杂志》2024年第6期417-424,共8页International Journal of Orthopaedics

基　　金：国家自然科学基金(82272579)。

摘　　要：目的 探讨掺镁聚左旋乳酸微球(PLLAMg)在大鼠肩袖损伤模型中的促进腱-骨愈合作用。方法 制备聚左旋乳酸微球(PLLAm)并将氧化镁和碳酸镁掺入,得到PLLAMg,提取大鼠肌腱干细胞(TDSC),体外利用活/死染色和CCK-8实验验证其生物相容性。取36只体质量200~300 g的SD大鼠建立急性肩袖损伤模型并进行手术修复,随机分为PLLAMg组、PLLAm组和对照组(n=12),并分别将PLLAMg、PLLAm注射入骨隧道和腱-骨界面处,而作为对照组则注射入等体积的生理盐水。在术后4周和8周,将大鼠安乐死后取下冈上肌腱-肱骨复合体并观察大体情况,固定脱钙后制作成石蜡切片进行组织学染色,另外将冈上肌腱-肱骨复合体置于生物力学实验装置中进行拉伸试验,记录其失效负荷和拉断时位移。结果 体外细胞活/死染色CCK-8试验表明PLLAMg无细胞毒性且对细胞增殖具有一定的促进作用。成功建立肩袖损伤模型后,术后4周和8周大鼠均存活。术后4周和8周,大体观察显示PLLAMg组附着处骨缺损明显减小,腱-骨界面愈合情况优于对照组。术后4、8周,HE染色显示PLLAMg组炎性细胞浸润明显减少,骨髓细胞聚集于骨髓腔内,骨小梁结构完整;Masson三色染色可见PLLAMg组出现大量排列整齐有序的胶原纤维,腱-骨界面胶原移行带面积增加,说明PLLAMg可促进腱-骨界面矿化纤维软骨;COL1免疫组化染色显示PLLAMg组染色面积、深度相比于对照组显著增加。术后4周和8周,生物力学检测发现PLLAMg组失效负荷较对照组显著增加,其刚度在术后8周同样增加,而在术后4周与对照组无统计学差异。结论 PLLAMg具有良好的生物相容性,可促进大鼠体内腱-骨界面愈合。PLLAMg联合手术的治疗方案对改善肩袖修复术后腱-骨界面瘢痕愈合,降低肩袖术后再撕裂具有巨大的潜力。Objective This study aimed to determine the effects of magnesium-doped polylactic acid microspheres(PLLAMgs)in promoting bone-tendon healing in a rotator cuff injury rat model.Methods Polylactic acid microspheres(PLLAms)were prepared and doped with magnesium oxide and magnesium carbonate to create the study material.Rat tendon-derived stem cells(TDSCs)were extracted and subjected to in vitro viability and proliferation assays using live/dead staining and CCK-8 experiments to verify the biocompatibility of PLLAMgs.Thirty-six SD rats weighing 200–300 g were used to establish an acute rotator cuff injury model.The rats were randomly divided into three groups(PLLAMg;PLLAm;and control)that underwent simple surgical repair.PLLAMgs and PLLAms were injected into the bone tunnel and tendon-bone interface,while the control group received an equivalent volume of saline.After 4 and 8 weeks postoperatively the rats were euthanized and the supraspinatus tendonhumerus complex was dissected for gross examination.Histologic staining was performed on decalcified paraffin sections.The biomechanical testing involved subjecting the supraspinatus tendon-humerus complex to tensile tests.Failure load and displacement were recorded.Results In vitro cell viability and CCK-8 assays demonstrated that PLLAMgs had no cytotoxicity and promoted cell proliferation.At 4 weeks and 8 weeks postoperatively the PLLAMg group had reduced bone defects at the attachment site and better tendon-bone interface healing compared to the control group.HE staining revealed significantly reduced inflammatory cell infiltration in the PLLAMg group at 4 and 8 weeks postoperatively.Bone marrow cells aggregated within the bone marrow cavity and trabecular bone structure remained intact.Masson trichrome staining showed well-organized collagen fibers at 4 and 8 weeks postoperatively with an increased collagen transition zone at the tendon-bone interface,which indicated enhanced mineralized fibrocartilage. COL-1 immunohistochemistry demonstrated a significantly increas

关 键 词：镁离子 微球 肩袖损伤 大鼠 腱-骨愈合 

分 类 号：R686[医药卫生—骨科学]