The Subacromial Bursa in Rotator Cuff Disease: Biological Insights From Preclinical In Vitro and In Vivo Studies—A Systematic Review

Background: The subacromial bursa (SAB) is traditionally viewed as a source of inflammation in rotator cuff (RC) disease, often leading to routine bursectomy; recent evidence suggests its potential as a biological resource. This systematic review aims to evaluate the biological properties of SAB and its role in RC pathophysiology and repair by synthesizing evidence from preclinical in vitro and in vivo studies. Methods: A systematic search was conducted across PubMed, Scopus, and Web of Science (January 2015–December 2026) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In vitro and in vivo preclinical studies investigating SAB were included. Main characteristics and findings of each included article were extracted. Risk of bias (RoB) was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tools. Results: Twenty-seven studies were included (21 in vitro, 3 in vivo, 3 combined). In vitro studies confirmed that SAB-derived cells possess mesenchymal stem cell-like properties, including high proliferative capacity and multilineage differentiation potential, often superior to bone marrow-derived cells. SAB cells demonstrated “biological plasticity”, responding to anabolic stimuli and pharmacological agents. In vivo models suggested that SAB preservation or cell transplantation facilitates histological and mechanical maturation of repaired tendons. Conclusions: From preclinical evidence, SAB emerged as a biologically active tissue that responds to inflammation and serves as a source of mesenchymal progenitor cells and bioactive factors, with the potential to enhance tendon healing. However, the available preclinical evidence is limited by methodological weaknesses and risks of bias. High-quality studies are needed to confirm efficacy and optimal indications its application in RC repair.