Abstract
Objectives
Bioprinting of bone and cartilage suffers from low mechanical properties. Here we have developed a unique inkjet bioprinting approach of creating mechanically strong bone and cartilage tissue constructs using poly(ethylene glycol) dimethacrylate, gelatin methacrylate, and human MSCs.
Results
The printed hMSCs were evenly distributed in the polymerized PEG-GelMA scaffold during layer-by-layer assembly. The procedure showed a good biocompatibility with >80% of the cells surviving the printing process and the resulting constructs provided strong mechanical support to the embedded cells. The printed mesenchymal stem cells showed an excellent osteogenic and chondrogenic differentiation capacity. Both osteogenic and chondrogenic differentiation as determined by specific gene and protein expression analysis (RUNX2, SP7, DLX5, ALPL, Col1A1, IBSP, BGLAP, SPP1, Col10A1, MMP13, SOX9, Col2A1, ACAN) was improved by PEG-GelMA in comparison to PEG alone. These observations were consistent with the histological evaluation.
Conclusions
Inkjet bioprinted-hMSCs in simultaneously photocrosslinked PEG-GelMA hydrogel scaffolds demonstrated an improvement of mechanical properties and osteogenic and chondrogenic differentiation, suggesting its promising potential for usage in bone and cartilage tissue engineering.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Catelas I, Sese N, Wu BM, Dunn JC, Helgerson S, Tawil B (2006) Human mesenchymal stem cell proliferation and osteogenic differentiation in fibrin gels in vitro. Tissue Eng 12:2385–2396
Cui X, Boland T (2009) Human microvasculature fabrication using thermal inkjet printing technology. Biomaterials 30:6221–6227
Cui X, Dean D, Ruggeri ZM, Boland T (2010) Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells. Biotechnol Bioeng 106:963–969
Cui X, Boland T, D’Lima DD, Lotz MK (2012a) Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul 6:149–155
Cui X, Breitenkamp K, Finn MG, Lotz M, D’Lima DD (2012b) Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Eng Part A 18:1304–1312
Cui X, Breitenkamp K, Lotz M, D’Lima D (2012c) Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation. Biotechnol Bioeng 109:2357–2368
Cui X, Hasegawa A, Lotz M, D’Lima D (2012d) Structured three-dimensional co-culture of mesenchymal stem cells with meniscus cells promotes meniscal phenotype without hypertrophy. Biotechnol Bioeng 109:2369–2380
Cui X, Gao G, Qiu Y (2013) Accelerated myotube formation using bioprinting technology for biosensor applications. Biotechnol Lett 35:315–321
Cui X, Gao G, Yonezawa T, Dai G (2014) Human cartilage tissue fabrication using three-dimensional inkjet printing technology. J Vis Exp 88:e51294. doi:10.3791/51294
Gao G, Schilling AF, Yonezawa T, Wang J, Dai G, Cui X (2014) Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells. Biotechnol J 9:1304–1311
Gao G, Yonezawa T, Hubbell K, Dai G, Cui X (2015) Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging. Biotechnol J. doi:10.1002/biot.201400635
Kim TK, Sharma B, Williams CG, Ruffner MA, Malik A, McFarland EG, Elisseeff JH (2003) Experimental model for cartilage tissue engineering to regenerate the zonal organization of articular cartilage. Osteoarthr Cartil 11:653–664
Lin-Gibson S, Bencherif S, Cooper JA, Wetzel SJ, Antonucci JM, Vogel BM, Horkay F, Washburn NR (2004) Synthesis and characterization of PEG dimethacrylates and their hydrogels. Biomacromolecules 5:1280–1287
Salinas CN, Anseth KS (2009) Decorin moieties tethered into PEG networks induce chondrogenesis of human mesenchymal stem cells. J Biomed Mater Res A 90:456–464
Sharma B, Williams CG, Kim TK, Sun DN, Malik A, Khan M, Leong K, Elisseeff JH (2007) Designing zonal organization into tissue-engineered cartilage. Tissue Eng 13:405–414
Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H (2000) Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules 1:31–38
Acknowledgments
The authors would like to acknowledge M.G. Finn, Kurt Breitenkamp, Lilo Creighton, Vivian Lee, Taylor Dorsey, and Diana Kim for constructive suggestions and technical support. This work was funded by New York Capital Region Research Alliance Grant, the Fundamental Research Funds for the Central Universities (WUT: 2015IB004), NSF 1011796, and Stemorgan Therapeutics R&D support (TERM002). The authors have no financial or commercial conflict of interest to declare.
Supplementary information
Supplementary Table 1—Engineering parameters of a modified HP DeskJet 500 printer and mass swelling ratio (Q) and equilibrium water content (M) of printed 10 % w/v PEGDMA (PEG), and 10 % w/v PEG with 1.5 % w/v GelMA (PEG-GelMA) (n = 3).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Gao, G., Schilling, A.F., Hubbell, K. et al. Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG-GelMA. Biotechnol Lett 37, 2349–2355 (2015). https://doi.org/10.1007/s10529-015-1921-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-015-1921-2