Scaffolds Derived from ECM Produced by Chondrogenically Induced Human MSC Condensates Support Human MSC Chondrogenesis

Osteoarthritis is a leading cause of disability affecting an increasing number of individuals. However, cartilage replacement therapies are inadequate, and better cartilage regeneration products must be developed. In this work, we describe a human mesenchymal stem cell (hMSC)-based approach for fabricating extracellular matrix (ECM) scaffolds from tissue-engineered cartilage sheets and then for inducing chondrogenesis of reseeded hMSCs within the ECM scaffolds. Two types of ECM scaffolds were fabricated: one from high-density hMSC sheets cultured with media-supplemented transforming growth factor beta-1 (TGF-β1; −MS) and the other from high-density hMSC sheets incorporated with TGF-β1-laden gelatin microspheres (+MS), which significantly enhance chondrogenesis within the sheet system. Interestingly, when scaffolds were reseeded with hMSCs, −MS scaffolds lead to significantly more glycosaminoglycan (GAG) accumulation than +MS scaffolds. Importantly, ECM scaffolds could be soak loaded with TGF-β1 to produce...