Effects of chondrogenic and osteogenic regulatory factors on composite constructs grown using human mesenchymal stem cells, silk scaffolds and bioreactors

Author:

Augst Alexander1,Marolt Darja1,Freed Lisa E1,Vepari Charu2,Meinel Lorenz12,Farley Michelle1,Fajardo Robert3,Patel Nipun3,Gray Martha1,Kaplan David L2,Vunjak-Novakovic Gordana1

Affiliation:

1. Harvard-MIT Division of Health Sciences and Technology77 Massachusetts Avenue, Cambridge, MA 02139, USA

2. Department of Biomedical Engineering, Tufts University4 Colby Street, Medford, MA 02155, USA

3. Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School330 Brookline Avenue, Boston, MA 02215, USA

Abstract

Human mesenchymal stem cells (hMSCs) isolated from bone marrow aspirates were cultured on silk scaffolds in rotating bioreactors for three weeks with either chondrogenic or osteogenic medium supplements to engineer cartilage- or bone-like tissue constructs. Osteochondral composites formed from these cartilage and bone constructs were cultured for an additional three weeks in culture medium that was supplemented with chondrogenic factors, supplemented with osteogenic factors or unsupplemented. Progression of cartilage and bone formation and the integration between the two regions were assessed by medical imaging (magnetic resonance imaging and micro-computerized tomography imaging), and by biochemical, histological and mechanical assays. During composite culture (three to six weeks), bone-like tissue formation progressed in all three media to a markedly larger extent than cartilage-like tissue formation. The integration of the constructs was most enhanced in composites cultured in chondrogenic medium. The results suggest that tissue composites with well-mineralized regions and substantially less developed cartilage regions can be generated in vitro by culturing hMSCs on silk scaffolds in bioreactors, that hMSCs have markedly higher capacity for producing engineered bone than engineered cartilage, and that chondrogenic factors play major roles at early stages of bone formation by hMSCs and in the integration of the two tissue constructs into a tissue composite.

Publisher

The Royal Society

Subject

Biomedical Engineering,Biochemistry,Biomaterials,Bioengineering,Biophysics,Biotechnology

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