Insulin-Functionalized Bioactive Fiber Matrices with Bone Marrow-Derived Stem Cells in Rat Achilles Tendon Regeneration.
Insulin-Functionalized Bioactive Fiber Matrices with Bone Marrow-Derived Stem Cells in Rat Achilles Tendon Regeneration.
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DOI：
10.1021/acsabm.2c00243
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发表时间：
2022-06-20
影响因子：
4.7
通讯作者：
Kumbar, Sangamesh G
中科院分区：
文献类型：
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作者：
Ramos, Daisy M;Abdulmalik, Sama;Arul, Michael R;Sardashti, Naseem;Banasavadi-Siddegowda, Yeshavanth Kumar;Nukavarapu, Syam P;Drissi, Hicham;Kumbar, Sangamesh G
在美国，每年约有一半的肌肉骨骼损伤涉及肌腱撕裂。肌腱本身细胞稀少且血管不丰富的环境使其容易受伤且愈合缓慢。肌腱组织工程策略通常使用仿生支架结合生物活性因子和/或细胞来促进愈合。美国食品药品监督管理局（FDA）批准的用于促进肌腱愈合的生长因子尚缺乏，这凸显了对安全有效生物活性因子的需求。我们之前的研究评估了胰岛素作为一种生物活性因子，并确定了促进间充质干细胞在体外存活、分裂和成腱的最佳剂量。本研究评估了有或无间充质干细胞的胰岛素功能化电纺纳米纤维基质在大鼠跟腱损伤模型中促进肌腱修复的能力。电纺纳米纤维基质用胰岛素进行功能化处理，有或无间充质干细胞培养，然后缝合到大鼠切断的跟腱上。我们在手术后4周和8周对大鼠肌腱进行分析，包括肌腱形态、胶原蛋白生成和力学性能。含有间充质干细胞的生物活性胰岛素功能化纤维基质在手术后4周和8周使Ⅰ型和Ⅲ型胶原蛋白显著增加。此外，这些基质在8周时支持再生肌腱组织中高度排列的胶原纤维。然而，治疗组和对照组再生组织在8周时具有相似的拉伸性能，且均低于天然跟腱。我们的初步结果证实了胰岛素功能化纤维基质在促进肌腱修复功能恢复所需的更高水平胶原蛋白合成和排列方面的益处。
Approximately half of annual musculoskeletal injuries in the US involve tendon tears. The naturally hypocellular and hypovascular tendon environment makes tendons injury-prone and heal slowly. Tendon tissue engineering strategies often use biomimetic scaffolds combined with bioactive factors and/or cells to enhance healing. FDA-approved growth factors to promote tendon healing are lacking, which highlights the need for safe and effective bioactive factors. Our previous work evaluated insulin as a bioactive factor and identified an optimal dose to promote in vitro mesenchymal stem cell survival, division, and tenogenesis. The present work evaluates the ability of insulin-functionalized electrospun nanofiber matrices with or without mesenchymal stem cells to enhance tendon repair in a rat Achilles injury model. Electrospun nanofiber matrices were functionalized with insulin, cultured with or without mesenchymal stem cells, and sutured to transected Achilles tendons in rats. We analyzed rat tendons 4 and 8 weeks after surgery for the tendon morphology, collagen production, and mechanical properties. Bioactive insulin-functionalized fiber matrices with mesenchymal stem cells resulted in significantly increased collagen I and III at 4 and 8 weeks postsurgery. Additionally, these matrices supported highly aligned collagen fibrils in the regenerated tendon tissue at 8 weeks. However, treatment- and control-regenerated tissues had similar tensile properties at 8 weeks, which were less than that of the native Achilles tendon. Our preliminary results establish the benefits of insulin-functionalized fiber matrices in promoting higher levels of collagen synthesis and alignment needed for functional recovery of tendon repair.