Mold-shaped, nanofiber scaffold-based cartilage engineering using human mesenchymal stem cells and bioreactor.
BACKGROUND
Mesenchymal stem cell (MSC)-based tissue engineering is a promising future alternative to autologous cartilage grafting. This study evaluates the potential of using MSCs, seeded into electrospun, biodegradable polymeric nanofibrous scaffolds, to engineer cartilage with defined dimensions and shape, similar to grafts used for subcutaneous implantation in plastic and reconstructive surgery.


METHODS
Human bone marrow derived MSCs seeded onto nanofibrous scaffolds and placed in custom-designed molds were cultured for up to 42 days in bioreactors. Chondrogenesis was induced with either transforming growth factor-beta1 (TGF-beta1) alone or in combination with insulin-like growth factor-I (IGF-I).


RESULTS
Constructs exhibited hyaline cartilage histology with desired thickness and shape as well as favorable tissue integrity and shape retention, suggesting the presence of elastic tissue. Time-dependent increase in cartilage matrix gene expression was seen in both types of culture: at Day 42, TGF-beta1/IGF-I treated cultures showed higher collagen Type 2 and aggrecan expression. Both culture conditions showed significant time-dependent increase in sulfated glycosaminoglycan and hydroxyproline contents. TGF-beta1/IGF-I-treated samples were significantly stiffer; with equilibrium compressive Young's modulus values reaching 17 kPa by Day 42.


CONCLUSIONS
The successful ex vivo development of geometrically defined cartilaginous construct using customized molding suggests the potential of cell-based cartilage tissue for reconstructive surgery.
Janjanin
Sasa
S
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-8022, USA.
Li
Wan-Ju
WJ
Morgan
Meredith T
MT
Shanti
Rabie M
RM
Tuan
Rocky S
RS
D020341:Absorbable Implants; D019149:Bioreactors; D001854:Bone Marrow Cells; D002356:Cartilage / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D059630:Mesenchymal Stem Cells; D049329:Nanostructures; D011108:Polymers; D011474:Prosthesis Design; D012038:Regeneration; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D011108:Polymers; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I