4.2 Article

Insulin-Functionalized Bioactive Fiber Matrices with Bone Marrow-Derived Stem Cells in Rat Achilles Tendon Regeneration

期刊

ACS APPLIED BIO MATERIALS
卷 5, 期 6, 页码 2851-2861

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsabm.2c00243

关键词

tendon tissue engineering; insulin; nanofiber matrices; growth factor alternative; stem cells; Achilles tendon

资金

  1. Connecticut Regenerative Medicine Research [Fund-15-RMB-UCHC-08]
  2. National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [R01EB020640, R01EB030060, 1R56NS122753]
  3. U.S. Army Medical Research Acquisition Activity (USAMRAA), through the CDMRP Peer Reviewed Medical Research Program [W81XWH2010321]
  4. U.S. Department of Defense (DOD) [W81XWH2010321] Funding Source: U.S. Department of Defense (DOD)

向作者/读者索取更多资源

Approximately half of musculoskeletal injuries in the US involve tendon tears. Tendon injuries are common and slow to heal due to the nature of tendon tissue. Insulin-functionalized nanofiber matrices have been found to enhance tendon repair when combined with mesenchymal stem cells. The matrices promote collagen synthesis and alignment, contributing to functional recovery of the tendon.
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.

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