Hybrid Bioprinting of Zonally Stratified Human Articular Cartilage Using Scaffold-Free Tissue Strands as Building Blocks

Yang Wu; Bugra Ayan; Kazim K Moncal; Youngnam Kang; Aman Dhawan; Srinivas V Koduru; Dino J Ravnic; Fadia Kamal; Ibrahim T Ozbolat

doi:10.1002/adhm.202001657

Hybrid Bioprinting of Zonally Stratified Human Articular Cartilage Using Scaffold-Free Tissue Strands as Building Blocks

Adv Healthc Mater. 2020 Nov;9(22):e2001657. doi: 10.1002/adhm.202001657. Epub 2020 Oct 19.

Authors

Yang Wu^{1

2}, Bugra Ayan^{1

2}, Kazim K Moncal^{1

2}, Youngnam Kang^{1

2}, Aman Dhawan³, Srinivas V Koduru^{4

5}, Dino J Ravnic⁴, Fadia Kamal^{6

7}, Ibrahim T Ozbolat^{1

2

8

9}

Affiliations

¹ Engineering Science and Mechanics Department, Penn State University, University Park, PA, 16802, USA.
² The Huck Institutes of the Life Sciences, Penn State University, University Park, PA, 16802, USA.
³ Department of Orthopaedics and Rehabilitation, Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, 17033, USA.
⁴ Department of Surgery, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, 17033, USA.
⁵ Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA, 17033, USA.
⁶ Center for Orthopedic Research and Translational Science, Department of Orthopedics and Rehabilitation, Penn State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, 17033, USA.
⁷ Department of Pharmacology, Penn State University, College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, 17033, USA.
⁸ Biomedical Engineering Department, Penn State University, University Park, PA, 16802, USA.
⁹ Materials Research Institute, Penn State University, University Park, PA, 16802, USA.

Abstract

The heterogeneous and anisotropic articular cartilage is generally studied as a layered structure of "zones" with unique composition and architecture, which is difficult to recapitulate using current approaches. A novel hybrid bioprinting strategy is presented here to generate zonally stratified cartilage. Scaffold-free tissue strands (TSs) are made of human adipose-derived stem cells (ADSCs) or predifferentiated ADSCs. Cartilage TSs with predifferentiated ADSCs exhibit improved mechanical properties and upregulated expression of cartilage-specific markers at both transcription and protein levels as compared to TSs with ADSCs being differentiated in the form of strands and TSs of nontransfected ADSCs. Using the novel hybrid approach integrating new aspiration-assisted and extrusion-based bioprinting techniques, the bioprinting of zonally stratified cartilage with vertically aligned TSs at the bottom zone and horizontally aligned TSs at the superficial zone is demonstrated, in which collagen fibers are aligned with designated orientation in each zone imitating the anatomical regions and matrix orientation of native articular cartilage. In addition, mechanical testing study reveals a compression modulus of ≈1.1 MPa, which is similar to that of human articular cartilage. The prominent findings highlight the potential of this novel bioprinting approach for building biologically, mechanically, and histologically relevant cartilage for tissue engineering purposes.

Keywords: adipose-derived stem cells; biofabrication; scaffold-free bioprinting; zonally stratified articular cartilage.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Bioprinting*
Cartilage, Articular*
Humans
Stem Cells
Tissue Engineering
Tissue Scaffolds*

Grants and funding

R01 AR071968/AR/NIAMS NIH HHS/United States