Microengineering the synovial membrane microenvironment for osteoarthritis research

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.