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rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model

  • Symposium: Biologics and Tissue Healing in Orthopaedics
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

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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Acknowledgments

We acknowledge Stephen Goldman PhD, for providing the collagen sponge material (ie, Type I collagen scaffold) from Kensey Nash, Inc (Exton, PA, USA). We also thank Ran Stark MD, for his assistance with the animal surgeries.

Author information

Authors and Affiliations

  1. Tissue Engineering, Regeneration, and Repair Program, Hospital for Special Surgery, New York, NY, USA

    David Kovacevic MD, Liang Ying DVM, John R. Ehteshami MD & Xiang-Hua Deng MD

  2. Sports Medicine and Shoulder Service, Hospital for Special Surgery, 525 East 71st Street, New York, NY, 10021, USA

    Lawrence V. Gulotta MD & Scott A. Rodeo MD

Authors
  1. David Kovacevic MD
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  2. Lawrence V. Gulotta MD
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  3. Liang Ying DVM
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  4. John R. Ehteshami MD
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  5. Xiang-Hua Deng MD
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  6. Scott A. Rodeo MD
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Corresponding author

Correspondence to Scott A. Rodeo MD.

Additional information

The institution of one of the authors (SAR) has received less than USD 10,000, in any one year, funding from BioMimetic Therapeutics, Inc (Franklin, TN, USA). One or more of the authors is a paid consultant for Biomet (Warsaw, IN, USA) (LVG) and Smith & Nephew (Memphis, TN, USA) (SAR), has stock or stock options in Cayenne Medical (Scottsdale, AZ, USA) (SAR), and is on the medical/orthopaedic publications editorial/governing board of the HSS Journal (LVG).

All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request.

Clinical Orthopaedics and Related Research ® neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use.

Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at the Hospital for Special Surgery, New York, NY, USA.

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Kovacevic, D., Gulotta, L.V., Ying, L. et al. rhPDGF-BB Promotes Early Healing in a Rat Rotator Cuff Repair Model. Clin Orthop Relat Res 473, 1644–1654 (2015). https://doi.org/10.1007/s11999-014-4020-0

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  • DOI: https://doi.org/10.1007/s11999-014-4020-0

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