Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair

C. N. Manning, A. G. Schwartz, W. Liu, J. Xie, N. Havlioglu, S. E. Sakiyama-Elbert, M. J. Silva, Y. Xia, R. H. Gelberman, S. Thomopoulos

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135 Scopus citations


Outcomes after tendon repair are often unsatisfactory, despite improvements in surgical techniques and rehabilitation methods. Recent studies aimed at enhancing repair have targeted the paucicellular nature of tendon for enhancing repair; however, most approaches for delivering growth factors and cells have not been designed for dense connective tissues such as tendon. Therefore, we developed a scaffold capable of delivering growth factors and cells in a surgically manageable form for tendon repair. Platelet-derived growth factor BB (PDGF-BB), along with adipose-derived mesenchymal stem cells (ASCs), were incorporated into a heparin/fibrin-based delivery system (HBDS). This hydrogel was then layered with an electrospun nanofiber poly(lactic-co-glycolic acid) (PLGA) backbone. The HBDS allowed for the concurrent delivery of PDGF-BB and ASCs in a controlled manner, while the PLGA backbone provided structural integrity for surgical handling and tendon implantation. In vitro studies verified that the cells remained viable, and that sustained growth factor release was achieved. In vivo studies in a large animal tendon model verified that the approach was clinically relevant, and that the cells remained viable in the tendon repair environment. Only a mild immunoresponse was seen at dissection, histologically, and at the mRNA level; fluorescently labeled ASCs and the scaffold were found at the repair site 9 days post-operatively; and increased total DNA was observed in ASC-treated tendons. The novel layered scaffold has the potential for improving tendon healing due to its ability to deliver both cells and growth factors simultaneously in a surgically convenient manner.

Original languageEnglish
Pages (from-to)6905-6914
Number of pages10
JournalActa Biomaterialia
Issue number6
StatePublished - Jun 2013


  • Electrospinning
  • Intrasynovial flexor tendon
  • Stem cells
  • Sustained delivery system
  • Tissue engineering


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