Tissue engineering of human-shaped mandibular condyles from adult mesenchymal stem cells

Treatment of degenerated or missing articular condyle represents a major orthopedic challenge. An entire articular condyle engineered from adult stem cells has the potential to overcome substantial deficiencies associated with grafting and prosthetic replacement procedures and provide an alternative therapeutic approach for total condylar replacement. The objective of this study was to tissue engineer osteochondral constructs in the shape of a human mandibular condyle from adult rat mesenchymal stem cells.; Isolated primary rat bone marrow mesenchymal stem cells (MSCs) were induced to differentiate into chondrogenic and osteogenic lineages in vitro and suspended in poly(ethylene glycol)-diacrylate (PEGDA) hydrogel solution containing photoinitiator. The hydrogel suspensions containing MSC-derived chondrogenic and osteogenic cells were molded into the shape of a cadaver adult human mandibular condyle and stratified via sequential hydrogel photopolymerization. The fabricated osteochondral constructs were implanted in the dorsum of immunodeficient mice for 4, 8, and 12 weeks.; De novo formation of osteochondral constructs in the shape of a human mandibular condyle occurred after 4, 8, and 12-week in vivo cultivation. Histological evaluation demonstrated two stratified layers of cartilaginous and osseous phenotypes. Parallel in vitro experiments demonstrated chondrogenesis and osteogenesis driven by MSC-treated chondrogenic and osteogenic cells, respectively. Upon nanoindentation with atomic force microscope, the in vitro incubated osteogenic hydrogel constructs demonstrated higher Young's modulus than the chondrogenic hydrogel constructs.; The present data demonstrate the feasibility of tissue engineering osteochondral constructs in the shape of a human mandibular condyle from adult rat MSCs and serve as a proof of concept for ultimate therapeutic goal of tissue-engineered replacement of an entire articular condyle via a single population of adult MSCs.