Standardized Effect Measures Informing Next-Generation Strategies for Mechanical Stimulation in Cartilage Tissue Engineering.

Abstract

Dynamic mechanical stimulation provides cues essential to mechanoadaptation, influencing extracellular matrix composition and functional properties. Cartilage tissue engineering implements a wide spectrum of stimulation modalities and loading parameters, yet the absence of standardization hinders direct comparison and limits investigation of optimal mechanical stimulation protocols. This systematic review summarizes published parameters of mechanical stimulation and applies standardized effect measures to compare their efficacy on matrix production in tissue-engineered cartilage. A total of 95 in vitro studies were included, covering six stimulation modalities (compression, tension, shear, hydrostatic pressure, fluid-induced shear, and combined stimuli) and chondrogenic outcomes (aggrecan and collagen II gene expression, glycosaminoglycan and collagen deposition, and compressive equilibrium modulus). The combined application of compression and shear was most effective, suggesting that complex loading patterns are potentially more beneficial for optimal cartilage mechanoadaptation. Loading dynamics and magnitude correlated with chondrogenic outcomes in meta-regression analysis, particularly for fluid-induced shear, which exhibited decreasing effects at higher intensities. Standardized effect measures enabled cross-study comparison despite wide methodological variability. A comprehensive in vitro comparison under rigorously controlled culture conditions, with precise understanding of sub-tissue mechanical stimuli, is essential for improving research reproducibility, optimizing mechanical microenvironments, and guiding bioreactor design for enhanced cartilage matrix development.