期刊
BIOMATERIALS
卷 228, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119579
关键词
Cartilage tissue engineering; ADSCs; Chondrocytes; Co-culture; Microribbons; Mechanical properties
资金
- NIH [R01DE024772]
- NSF CAREER award [CBET-1351289]
- California Institute for Regenerative Medicine Tools and Technologies Award [RT3-07804]
- Stanford Bio-X Interdisciplinary Initiative Seed grant
- Stanford Child Health Research Institute Faculty Scholar Award
- NSF Graduate Research Fellowship Program
- Stanford Interdisciplinary Graduate Fellowship from the Stanford Bio-X program
Juvenile chondrocytes are robust in regenerating articular cartilage, but their clinical application is hindered by donor scarcity. Stem cells offer an abundant autologous cell source but are limited by slow cartilage deposition with poor mechanical properties. Using 3D co-culture models, mixing stem cells and chondrocytes can induce synergistic cartilage regeneration. However, the resulting cartilage tissue still suffers from poor mechanical properties after prolonged culture. Here we report a microribbon/hydrogel composite scaffold that supports synergistic interactions using co-culture of adipose-derived stem cells (ADSCs) and neonatal chondrocytes (NChons). The composite scaffold is comprised of a macroporous, gelatin microribbon (mu RB) scaffolds filled with degradable nanoporous chondroitin sulfate (CS) hydrogel. We identified an optimal CS concentration (6%) that best supported co-culture synergy in vitro. Furthermore, 7 days of TGF-beta 3 exposure was sufficient to induce catalyzed cartilage formation. When implanted in vivo, mu RB/CS composite scaffold supported over a 40-fold increase in compressive moduli of cartilage produced by mixed ADSCs/NChons to similar to 330 kPa, which surpassed even the quality of cartilage produced by 100% NChons. Together, these results validate mu RB/CS composite as a promising scaffold for cartilage regeneration using mixed populations of stem cells and chondrocytes.
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