Pharmacologic Enhancement of Rotator Cuff Repair: A Narrative Review

Abstract

Introduction As rotator cuff repairs (RCRs) are among the most common procedures in upper extremity orthopedics, healing augmentation using pharmacologic enhancement of the repaired rotator cuff muscle is of particular interest. Objective The purpose of this study is to review the current understanding of Matrix Metalloproteinases (MMPs), Doxycycline, Testosterone, Estrogen, Growth hormone/ IGF-1, Vitamin D, and Vitamin C as a means to mitigate deleterious effects and propagate factors that support healing following RCR. Methods A review of English language articles in PubMed and Medline was conducted in December of 2020. All articles describing the current understanding of the aforementioned therapies were reviewed. Studies were excluded if they were non-English or reported incomplete results. Results Matrix metalloproteinases (MMP’s) are fundamental to the healing process after rotator cuff tears through a delicate balance of various proteases that can be modulated by doxycycline through inhibition. While testosterone has shown to induce replication and differentiation of the tendon stem-cells, estrogen agonists have been shown to decrease inflammation and muscle atrophy. Though growth hormone being associated with elevated collagen synthesis and decreased anoxic damage when present, clinical studies have shown inconclusive and adverse effects on rotator cuff healing. Patients with Vitamin D deficiency have shown to have increased fatty infiltration in rotator cuff muscle while Vitamin C functions as an antioxidant that increases collagen and fibroblast proliferation. Conclusion As manipulation of pharmacologic factors shows potential for enhancing healing following RCRs, future studies are needed to establish a viable augmentation strategy to improve patient outcomes

Recent Advances in the Use of Stem Cells in Tissue Engineering and Adjunct Therapies for Tendon Reconstruction and Future Perspectives

“…Another possibility for increasing the contribution of IGF-1 to tendon repair is the use of an IGF-1-embedded matrix. In a study on IGF-1 pegylation, the researchers used a copolymer matrix based on poly(L-lactide)-copoly(ε-caprolactone) with various modifications of embedded IGF-1 in a rat model of a rotator defect [131]. Application of the PEG-IGF-1m matrix led to enhanced in the biomechanical properties of the tissue.…”

Role of oxidative stress in the concurrent development of osteoporosis and tendinopathy: Emerging challenges and prospects for treatment modalities

“…Oxidative stress significantly influences the pathophysiological mechanisms of osteoporosis and tendinopathy co‐morbidities, highlighting antioxidant therapy as a potential treatment approach. 9 , 19 We have thoroughly explored how oxidative stress contributes to osteoporosis and tendon diseases. Next, let's delve into how antioxidants function in the treatment of these diseases and their impact on human health.…”

“… 17 , 18 Early‐stage tendinopathy is usually managed with conservative treatments like medication, mechanical loading and shockwave therapy, whereas more advanced cases may require surgical intervention. 19 , 20 However, conservative treatments often provide only temporary relief, and surgery carries risks like infection, joint stiffness, and the possibility of tendon re‐tearing, significantly impacting the patient's quality of life. 21 , 22 The high incidence of tendinopathy, its stubborn nature, and the risk of permanent functional damage contribute to a substantial economic burden globally.…”

Estrogen and testosterone supplementation improves tendon healing and functional recovery after rotator cuff repair

“…Testa et al performed an insurance database study and determined that patients prescribed testosterone had a significantly elevated risk for to undergoing a RCR as well as a re‐repair suggesting patients deficient in testosterone requiring treatment may be at‐risk for rotator cuff tearing 20 . Testosterone has been shown to increase tendon stem cell number and differentiation while estrogen agonists have been shown to decrease muscle atrophy in the setting of chronic rotator cuff tears 21 . We previously established a murine model of RCR and demonstrated that a potent estrogen receptor agonist (diethylstilbestrol) improved the healing based on histological and molecular analyses 17,22 .…”

“…20 Testosterone has been shown to increase tendon stem cell number and differentiation while estrogen agonists have been shown to decrease muscle atrophy in the setting of chronic rotator cuff tears. 21 We previously established a murine model of RCR and demonstrated that a potent estrogen receptor agonist (diethylstilbestrol) improved the healing based on histological and molecular analyses. 17,22 We have shown an association between sex hormone deficiency and the requirement for RCR utilizing a large insurance database.…”