We hypothesize that the combination of mechanical loading with hypoxia culture and TGF-β3 growth factor withdrawal will promote stable, non-hypertrophic chondrogenesis of hBM-MSC embedded in an HA-hydrogel. To this end, we first assessed static hypoxia culture with growth factor withdrawal against static normoxia (20% O2) culture at the global transcriptome and tissue matrix level. We then assess two modalities of mechanical loading (dynamic compression, DC and cyclic hydrostatic pressure, CHP) with growth factor withdrawal against static culture, all under hypoxia. Results showed that Mechanical stimulation and TGF-β3 withdrawal under hypoxia promoted a strong chondrogenic and non-hypertrophic phenotype of hBM-MSC. Overall design: Tissue-engineered constructs were made from frozen human BM-MSCs seeded on HyStem-C hydrogel. Constructs were precultured for three weeks in a 3% oxygen (HYP) condition with the supplement of TGF-β3. After pre-culture, two separate experiments were conducted. In experiment I, constructs were cultured in 3% and 20% (NRX) oxygen environment with/without the supplement with TGF-β3 for 3 weeks. In experiment II, constructs were cultured under dynamic compression or cyclic hydrostatic pressure with/without the supplement with TGF-β3 for 3 weeks. After the 6 weeks period, constructs were assessed via histology, immunofluorescence, GAG/DNA assays, RNA sequencing, and testing of mechanical properties.