Distinct effects of platelet-rich plasma and BMP13 on rotator cuff tendon injury healing in a rat model

Joseph D Lamplot, Michael Angeline, Jovito Angeles, Maureen Beederman, Eric Wagner, Farbod Rastegar, Bryan Scott, Christian Skjong, Daniel Mass, Richard Kang, Sherwin Ho, Lewis L Shi
American Journal of Sports Medicine 2014, 42 (12): 2877-87

BACKGROUND: Although platelet-rich plasma (PRP) is used clinically to augment tendon healing, bone morphogenetic protein-13 (BMP13) may provide a better therapeutic avenue to improve early tendon healing and repair.

HYPOTHESIS: Exogenous expression of BMP13 in tenocytes will up-regulate genes involved in tendon healing. Direct delivery of adenovirus-mediated BMP13 (AdBMP13) into the injured rat supraspinatus tendon will increase biomechanical properties.

STUDY DESIGN: Controlled laboratory study.

METHODS: Exogenous expression of BMP13 and the major growth factors in PRP (transforming growth factor-β1 [TGF-β1], vascular endothelial growth factor-A [VEGF-A], and platelet-derived growth factor-BB [PDGF-BB]) was accomplished by using recombinant adenoviral vectors. The expression of tendon- and matrix-associated genes in growth factor-treated tenocytes was analyzed by use of semiquantitative reverse-transcription polymerase chain reaction. A total of 32 rats with supraspinatus defect were divided into 4 groups and injected with adenovirus-containing green fluorescent protein (AdGFP; negative control), PRP, AdBMP13, or PRP+AdBMP13. All rats were sacrificed at 2 weeks after surgery, and tendons were harvested for biomechanical testing and histologic analysis.

RESULTS: BMP13 up-regulated type III collagen expression compared with AdGFP control and PRP growth factors (P < .01). BMP13 and PRP growth factors each up-regulated fibronectin expression (P < .01). There was an increase in stress to failure in each of the 3 treatment groups (P < .05 for PRP; P < .01 for AdBMP13 or PRP+AdBMP13) compared with AdGFP control. AdBMP13 demonstrated higher stress to failure than did the PRPs (P < .01). The addition of PRP did not increase the BMP13-enhanced stress to failure or stiffness. The biomechanical results were further supported by histologic analysis of the retrieved samples.

CONCLUSION: Exogenous expression of BMP13 enhances tendon healing more effectively than PRP as assessed by tendon- and matrix-associated gene expression, biomechanical testing, and histologic analysis.

CLINICAL RELEVANCE: While PRP is used in the clinical setting, BMP13 may be explored as a superior biofactor to improve rotator cuff tendon healing and reduce the incidence of retears.

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