Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model.
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.
Department of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus Box 8233, St. Louis, Missouri 63110, USA.
Cionne N
CN
Manning
H Mike
HM
Kim
Shelly
S
Sakiyama-Elbert
Leesa M
LM
Galatz
Necat
N
Havlioglu
Stavros
S
Thomopoulos
D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology; D001842:Bone and Bones / Q000502:physiology*; D002921:Cicatrix / Q000517:prevention & control; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D015552:Injections, Intralesional / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000187:drug effects / Q000502:physiology; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000188:drug therapy* / Q000503:physiopathology; D053782:Transforming Growth Factor beta3 / Q000493:pharmacokinetics / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D053782:Transforming Growth Factor beta3