Osteoarthritis (OA) is a multifactorial joint disease characterized by cartilage degradation, subchondral bone remodeling, synovitis, and cartilage matrix degradation. The synovial membrane plays a pivotal role in the progression of OA through low-grade inflammation and secretion of catabolic enzymes under altered mechanical homeostasis. While widely used to study OA pathogenesis and therapies, in vitro models (e.g. 2D synoviocyte co-cultures) frequently lack critical aspects of the in vivo synovial microenvironment, such as cellular heterogeneity, physiologically relevant mechanical stress, and dynamic cell-matrix crosstalk. These shortcomings reduce their translational value. This translational gap indicates the need for advanced 3D microengineered platforms that integrate patient-specific cells, biomechanical elements, and real-time biosensing to bridge in vitro findings to clinical outcomes. Recent advances in microengineering offer innovative in vitro systems such as OA synovium-on-a-chip, 3D-printed constructs, and hydrogel-based organoids that recapitulate key features of the synovial microenvironment. These tools enable precise control over mechanical stimuli, matrix composition, and cell-cell signaling. This review summarizes the microenvironment of the OA synovium, critiques existing model systems, and highlights emerging microengineering strategies aimed at better mimicking OA pathophysiology and advancing translational research.
Pak et al. (Wed,) studied this question.