Bioreactor-Induced Compression in Scaffolds for the Enhancement of Cartilage Regeneration: A Systematic Review

This systematic review evaluates how bioreactor-delivered mechanical compressive stimulation in engineered cartilage scaffolds influences extracellular matrix (ECM) biosynthesis and cartilage homeostasis and seeks to clarify the conditions and parameters necessary to enhance engineered cartilage formation.

A systematic literature search was developed and carried out in the MEDLINE, EMBASE, Web of Science, and Scopus databases from each database's inception to December 2024. In vitro studies reporting on bioreactors' compression effects on 3D tissue-engineered cartilage scaffolds, focusing on ECM assessment and cellular components, were included. Bioreactor-induced compression effects on ECM production, cell viability, and gene expression in chondrocytes and mesenchymal stem cells. Methodological quality was evaluated using an assessment tool specific to in vitro studies, evaluating the quality of reporting, replicability, and internal and external validity.

Following PRISMA guidelines, 30 in vitro studies were included for analysis of information. The findings reveal that mechanical stimulation, particularly cyclic compression (5-20% strain at 0.5-1 Hz), significantly improves ECM composition, with increases in glycosaminoglycans and type II collagen, while reducing hypertrophic markers.

Optimal bioreactor conditions were found to vary depending on cell type, scaffold material, and loading parameters, emphasizing the importance of tailored approaches. Additionally, biomaterials mimicking native cartilage properties enhanced the outcomes of mechanical stimulation by supporting cell differentiation and ECM deposition.