title: Spatially organized differentiation of mesenchymal stem cells within biphasic microparticle-incorporated high cell density osteochondral tissues.
abstract: Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem cells (hMSC) have the unique capacity to generate the complex tissues of the osteochondral interface. Utilizing a scaffold-free hMSC system, biphasic osteochondral constructs are incorporated with two types of growth factor-releasing microparticles to enable spatially organized differentiation. Gelatin microspheres (GM) releasing transforming growth factor-β1 (TGF-β1) combined with hMSC form the chondrogenic phase. The osteogenic phase contains hMSC only, mineral-coated hydroxyapatite microparticles (MCM), or MCM loaded with bone morphogenetic protein-2 (BMP-2), cultured in medium with or without BMP-2. After 4 weeks, TGF-β1 release from GM within the cartilage phase promotes formation of a glycosaminoglycan- and type II collagen-rich matrix, and has a local inhibitory effect on osteogenesis. In the osteogenic phase, type X collagen and osteopontin are produced in all conditions. However, calcification occurs on the outer edges of the chondrogenic phase in some constructs cultured in media containing BMP-2, and alkaline phosphatase levels are elevated, indicating that BMP-2 releasing MCM provides better control over region-specific differentiation. The production of complex, stem cell-derived osteochondral tissues via incorporated microparticles could enable earlier implantation, potentially improving outcomes in the treatment of osteochondral defects.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Loran D
authors.initials: LD
authors.lastname: Solorio
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Phillips
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: McMillan
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Christina W
authors.initials: CW
authors.lastname: Cheng
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Phuong N
authors.initials: PN
authors.lastname: Dang
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Samorezov
authors.affiliation: Departments of Biomedical Engineering and Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53706, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yu
authors.affiliation: Departments of Biomedical Engineering and Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53706, USA.|AO Foundation Collaborative Research Center, Clavadelerstrasse 8, Davos, 7270, Switzerland.
authors.forename: William L
authors.initials: WL
authors.lastname: Murphy
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.|AO Foundation Collaborative Research Center, Clavadelerstrasse 8, Davos, 7270, Switzerland.|Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
authors.forename: Eben
authors.initials: E
authors.lastname: Alsberg
mesh_terms: D000328:Adult; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002356:Cartilage; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D024043:Collagen Type II / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D053773:Transforming Growth Factor beta1
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D024043:Collagen Type II; D006025:Glycosaminoglycans; D053773:Transforming Growth Factor beta1; D005780:Gelatin; D017886:Durapatite
keywords: BMP (bone morphogenetic protein); TGF (transforming growth factor); bone; cartilage; hydroxyapatite