Articular Cartilage Tissue Engineering: Cells, Bioinstructive Scaffolds, Immunological Microenvironment, and Emerging...

Focal articular cartilage defects retain limited intrinsic repair capacity owing to the avascular, alymphatic and aneural nature of hyaline cartilage. Marrow-stimulation procedures often generate mechanically inferior fibrocartilage with declining benefit within 2-5 years in larger or high-demand lesions, while matrix-induced autologous chondrocyte implantation (MACI) achieves durable 10-year benefit but remains constrained by two-stage logistics, in vitro dedifferentiation and cost. This review integrates the cellular, biomaterial, biochemical and immunological dimensions of articular cartilage tissue engineering with quantitative benchmarks and a critical reading of failure modes, scalability and regulatory standing. We benchmark MACI against single-stage chondron- and progenitor-based therapies; examine mesenchymal stromal cells (MSCs) from bone marrow, adipose, synovium and the infrapatellar fat pad with a mechanistic dissection of the Wnt/β-catenin, IHH-PTHrP, RUNX2/MEF2C and HIF-1α inputs driving hypertrophic drift; reframe scaffolds as bioinstructive environments delivering mechanical, biochemical and tribological cues, including stimuli-responsive and 4D-printed systems and low-intensity pulsed ultrasound (LIPUS) as a non-invasive adjunct; develop the immunological dialogue between altered native cartilage, the infrapatellar fat pad-synovium unit and engineered constructs; and appraise CRISPR-based cell engineering and artificial-intelligence applications in biofabrication. We classify the principal approaches into four explicit translational tiers so that the evidentiary standing of each strategy is transparent. Translation will be paced by standardised potency assays, immune-aware construct design and robust long-term in vivo evidence.