Chondrogenic, hypertrophic, and osteochondral differentiation of human mesenchymal stem cells on three‐dimensionally woven scaffolds

Year: 2019

Type: article

Abstract: The development of mechanically functional cartilage and bone tissue constructs of clinically relevant size, as well as their integration with native tissues, remains an important challenge for regenerative medicine. The objective of this study was to assess adult human mesenchymal stem cells (MSCs) in large, three-dimensionally woven poly(ε-caprolactone; PCL) scaffolds in proximity to viable bone, both in a nude rat subcutaneous pouch model and under simulated conditions in vitro. In Study I, various scaffold permutations-PCL alone, PCL-bone, "point-of-care" seeded MSC-PCL-bone, and chondrogenically precultured Ch-MSC-PCL-bone constructs-were implanted in a dorsal, ectopic pouch in a nude rat. After 8 weeks, only cells in the Ch-MSC-PCL constructs exhibited both chondrogenic and osteogenic gene expression profiles. Notably, although both tissue profiles were present, constructs that had been chondrogenically precultured prior to implantation showed a loss of glycosaminoglycan (GAG) as well as the presence of mineralization along with the formation of trabecula-like structures. In Study II of the study, the GAG loss and mineralization observed in Study I in vivo were recapitulated in vitro by the presence of either nearby bone or osteogenic culture medium additives but were prevented by a continued presence of chondrogenic medium additives. These data suggest conditions under which adult human stem cells in combination with polymer scaffolds synthesize functional and phenotypically distinct tissues based on the environmental conditions and highlight the potential influence that paracrine factors from adjacent bone may have on MSC fate, once implanted in vivo for chondral or osteochondral repair.

Source: Journal of Tissue Engineering and Regenerative Medicine

DOI: 10.1002/term.2899

Authors: Benjamin L. Larson, Sarah N. Yu, Hyoungshin Park, Bradley T. Estes, Franklin T. Moutos, Cameron J. Bloomquist, Patrick B. Wu, Jean F. Welter, Robert Langer, Farshid Guilak, Lisa E. Freed

Institutions: Koch Institute for Integrative Cancer Research At MIT, MIT Media Lab, Massachusetts Institute of Technology, Cytex Therapeutics (United States), Case Western Reserve University, Washington University in St. Louis, Shriners Hospitals for Children - St. Louis

Language: English

Topic: Bone Tissue Engineering Materials

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Arthritis Foundation, Nancy Taylor Foundation for Chronic Diseases, AO Foundation, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering

OpenAlex ID: W2945962488