rhPDGF-BB promotes early healing in a rat rotator cuff repair model

David Kovacevic, Lawrence V Gulotta, Liang Ying, John R Ehteshami, Xiang-Hua Deng, Scott A Rodeo
Clinical Orthopaedics and related Research 2015, 473 (5): 1644-54

BACKGROUND: Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period.

QUESTIONS/PURPOSES: Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing.

METHODS: Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct.

RESULTS: The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 µg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13.3 ± 3.2 N/mm, p = 0.01; 100 µg/mL PDGF: 25.7 ± 6.1 N, p = 0.005 and 11.6 ± 3.3 N/mm, p = 0.01; 300 µg/mL PDGF: 27 ± 6.9 N, p = 0.014 and 12.7 ± 4.1 N/mm, p = 0.01).

CONCLUSIONS: rhPDGF-BB delivery on a collagen scaffold enhanced cellular proliferation and angiogenesis during the early phase of healing, but this did not result in either a more structurally organized or stronger attachment site at later stages of healing. The collagen scaffold had a detrimental effect on healing strength at 28 days, and its relatively larger size compared with the rat tendon may have caused mechanical impingement and extrinsic compression of the healing tendon. Future studies should be performed in larger animal models where healing occurs more slowly.

CLINICAL RELEVANCE: Augmenting the healing environment to improve the structural integrity and to reduce the retear rate after rotator cuff repair may be realized with continued understanding and optimization of growth factor delivery systems.

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