Andrei Demkov

Background: Rotator cuff (RC) injuries are prevalent among orthopedic pathologies, significantly contributing to the surgical burden each year.¹ These injuries exhibit a spectrum of severity from minor partial-thickness tears to extensive, retracted disruptions. Typically addressed through arthroscopic techniques, the recurrence of tears post-repair varies widely; smaller tears exhibit approximately a 20% re-rupture rate, while massive tears can experience re-rupture rates as high as 94%, according to some studies.² In contrast, proximal hamstring tears, more common in young, athletic individuals, show markedly better prognosis, with a re-rupture rate below 3%.^3,4 This divergence largely stems from the differential in preoperative musculotendinous conditions—hamstring injuries occur in patients with generally healthier tissue quality, whereas RC tears are increasingly frequent in aging individuals, particularly over 70 years, who often present significant muscular atrophy, a condition potentiated by cellular aging.^5–7 This stark contrast in clinical outcomes has spurred a diverse array of therapeutic approaches, which will be critically evaluated here.

Search Methods: PubMed searches including, but not limited to the terms: “rotator cuff atrophy,” “rotator cuff re-rupture,” and “tendon atrophy.”

Results: Current interventions targeting musculotendinous atrophy and senescence fall into three primary categories: pharmacological, biological, and cellular therapies. Pharmacological strategies have included the use of a metformin and leucine cocktail, which has shown efficacy in mitigating atrophy in cultured cells.⁸ However, while other pharmacological agents, both anabolic and anti-catabolic, have been explored, the former often introduces systemic side effects, and the latter does not rectify pre-existing atrophy. Biological treatments, particularly platelet-rich plasma injections, mirror the limitations of anti-catabolics, offering insufficient benefits for perioperative care.⁹ Conversely, cellular therapies emerge as the most promising, with mesenchymal stromal cells (MSCs) frequently employed in regenerative protocols. In their undifferentiated state, MSCs primarily act by secreting growth factors, similarly to PRP.⁹ They do, however, hold potential for tenogenic differentiation through mechanotransduction.¹⁰ Certain studies have shown promising results in tenogenic differentiation that would be necessary to rejuvenate senescent patient tissues.^11,12

Conclusions: Despite advances in pharmacological and biological therapies, the prevailing medical protocols inadequately address tissue atrophy and senescence associated with rotator cuff injuries. The rejuvenation of RC tissues through tenogenic differentiation of MSCs presents a viable strategy to diminish re-rupture rates in older adults with significant tears. Further research is imperative to refine MSC differentiation protocols and to investigate combined treatments that integrate cellular and biological therapies to enhance clinical outcomes.

Works Cited:

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