Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model

Cionne N. Manning, Hyun-Min Mike Kim, Shelly Sakiyama-Elbert, Leesa M. Galatz, Necat Havlioglu, Stavros Thomopoulos

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Despite advances in surgical technique, rotator cuff repairs are plagued by a high rate of failure. This failure rate is in part due to poor tendon-to-bone healing; rather than regeneration of a fibrocartilaginous attachment, the repair is filled with disorganized fibrovascular (scar) tissue. Transforming growth factor beta 3 (TGF-β3) has been implicated in fetal development and scarless fetal healing and, thus, exogenous addition of TGF-β3 may enhance tendon-to-bone healing. We hypothesized that: TGF-β3 could be released in a controlled manner using a heparin/fibrin-based delivery system (HBDS); and delivery of TGF-β3 at the healing tendon-to-bone insertion would lead to improvements in biomechanical properties compared to untreated controls. After demonstrating that the release kinetics of TGF-β3 could be controlled using a HBDS in vitro, matrices were incorporated at the repaired supraspinatus tendon-to-bone insertions of rats. Animals were sacrificed at 14-56 days. Repaired insertions were assessed using histology (for inflammation, vascularity, and cell proliferation) and biomechanics (for structural and mechanical properties). TGF-β3 treatment in vivo accelerated the healing process, with increases in inflammation, cellularity, vascularity, and cell proliferation at the early timepoints. Moreover, sustained delivery of TGF-β3 to the healing tendon-to-bone insertion led to significant improvements in structural properties at 28 days and in material properties at 56 days compared to controls. We concluded that TGF-β3 delivered at a sustained rate using a HBDS enhanced tendon-to-bone healing in a rat model.

Original languageEnglish (US)
Pages (from-to)1099-1105
Number of pages7
JournalJournal of Orthopaedic Research
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2011

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

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    Manning, C. N., Kim, H-M. M., Sakiyama-Elbert, S., Galatz, L. M., Havlioglu, N., & Thomopoulos, S. (2011). Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model. Journal of Orthopaedic Research, 29(7), 1099-1105. https://doi.org/10.1002/jor.21301