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

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-b3) has been implicated in fetal development and scarless fetal healing and, thus, exogenous addition of TGF-b3 may enhance tendon-to-bone healing. We hypothesized that: TGF-b3 could be released in a controlled manner using a heparin/fibrin-based delivery system (HBDS); and delivery of TGF-b3 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-b3 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-b3 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-b3 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-b3 delivered at a sustained rate using a HBDS enhanced tendon-to-bone healing in a rat model. ß

Biological augmentation of rotator cuff repair using bFGF-loaded electrospun poly(lactide-co-glycolide) fibrous membranes

“…Several recent investigations showed improvements or no detrimental effects on mechanical properties using polymer scaffolds 32,33 and heparin/fibrin-based systems. 34 In this study, local application of the PLGA membrane did result in greater ultimate load-to-failure and stiffness at 4 weeks. Additionally, after 8 weeks, mechanical strength of the supraspinatus tendon-bone construct augmented with bFGF-PLGA membrane increased remarkably.…”

“…33 Manning et al used a heparin/fibrin-based gel as an overlay to deliver transforming growth factor-b3 (TGF-b3) to rat supraspinatus injury and repair. 34 Inclusion of TGF-b3 in the scaffold improved mechanical properties, but scaffolds without TGF-b3 did not improve compared with repair-only controls. In multiple investigations, porcine small intestine submucosa has been used to augment repair, but these results showed no change compared with repair-only controls, nor were there improvements in mechanical properties over time after repair and implantation.…”

Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model

“…For rats in the injury-and-repair groups, the supraspinatus tendon was sharply severed from the humeral head and was repaired bilaterally in each animal, as previously described 23 . Operatively and nonoperatively treated animals either were left untreated (the CTL group) or were administered Scl-Ab (Scl-Ab VI; Amgen).…”

Factors affecting healing after arthroscopic rotator cuff repair

“…Numerous growth factors have been shown to improve proliferation and collagen secretion of tenocytes in vitro including basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor-b [70][71][72][73][74] . Platelet-rich plasma (PRP) is a fraction of whole blood containing high platelet counts that release these various growth factors when activated.…”