Direct human cartilage repair using three-dimensional bioprinting technology.

Current cartilage tissue engineering strategies cannot as yet fabricate new tissue that is indistinguishable from native cartilage with respect to zonal organization, extracellular matrix composition, and mechanical properties. Integration of implants with surrounding native tissues is crucial for long-term stability and enhanced functionality. In this study, we developed a bioprinting system with simultaneous photopolymerization capable for three-dimensional (3D) cartilage tissue engineering. Poly(ethylene glycol) dimethacrylate (PEGDMA) with human chondrocytes were printed to repair defects in osteochondral plugs (3D biopaper) in layer-by-layer assembly. Compressive modulus of printed PEGDMA was 395.73±80.40 kPa, which was close to the range of the properties of native human articular cartilage. Printed human chondrocytes maintained the initially deposited positions due to simultaneous photopolymerization of surrounded biomaterial scaffold, which is ideal in precise cell distribution for anatomic cartilage engineering. Viability of printed human chondrocytes increased 26% in simultaneous polymerization than polymerized after printing. Printed cartilage implant attached firmly with surrounding tissue and greater proteoglycan deposition was observed at the interface of implant and native cartilage in Safranin-O staining. This is consistent with the enhanced interface failure strength during the culture assessed by push-out testing. Printed cartilage in 3D biopaper had elevated glycosaminoglycan (GAG) content comparing to that without biopaper when normalized to DNA. These observations were consistent with gene expression results. This study indicates the importance of direct cartilage repair and promising anatomic cartilage engineering using 3D bioprinting technology.

[1]  P. Benya,et al.  Independent regulation of collagen types by chondrocytes during the loss of differentiated function in culture , 1978, Cell.

[2]  V C Mow,et al.  Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content. , 1982, The Journal of bone and joint surgery. American volume.

[3]  D. Buttle,et al.  Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. , 1986, Biochimica et biophysica acta.

[4]  R. Maier,et al.  Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases. , 1993, The Journal of biological chemistry.

[5]  M J Glimcher,et al.  Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. , 1993, The Journal of bone and joint surgery. American volume.

[6]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[7]  Helen Muir,et al.  The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[8]  R. Ochs,et al.  Chondrocyte apoptosis induced by nitric oxide. , 1995, The American journal of pathology.

[9]  J. Elisseeff,et al.  Transdermal photopolymerization of poly(ethylene oxide)-based injectable hydrogels for tissue-engineered cartilage. , 1999, Plastic and reconstructive surgery.

[10]  S J Bryant,et al.  Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro , 2000, Journal of biomaterials science. Polymer edition.

[11]  J. Elisseeff,et al.  Photoencapsulation of chondrocytes in poly(ethylene oxide)-based semi-interpenetrating networks. , 2000, Journal of biomedical materials research.

[12]  S. Bryant,et al.  Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. , 2002, Journal of biomedical materials research.

[13]  Mohammad Masoud Mohebi,et al.  A drop-on-demand ink-jet printer for combinatorial libraries and functionally graded ceramics. , 2002, Journal of combinatorial chemistry.

[14]  E B Hunziker,et al.  Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. , 2002, Osteoarthritis and cartilage.

[15]  E B Hunziker,et al.  Quantitative structural organization of normal adult human articular cartilage. , 2002, Osteoarthritis and cartilage.

[16]  C. Kaps,et al.  BMP2 initiates chondrogenic lineage development of adult human mesenchymal stem cells in high-density culture. , 2003, Differentiation; research in biological diversity.

[17]  J. Elisseeff,et al.  Experimental model for cartilage tissue engineering to regenerate the zonal organization of articular cartilage. , 2003, Osteoarthritis and cartilage.

[18]  S. Bryant,et al.  Crosslinking Density Influences Chondrocyte Metabolism in Dynamically Loaded Photocrosslinked Poly(ethylene glycol) Hydrogels , 2004, Annals of Biomedical Engineering.

[19]  Sheng Lin-Gibson,et al.  Synthesis and characterization of PEG dimethacrylates and their hydrogels. , 2004, Biomacromolecules.

[20]  Tao Xu,et al.  Viability and electrophysiology of neural cell structures generated by the inkjet printing method. , 2006, Biomaterials.

[21]  Xiaofeng Cui,et al.  Application of inkjet printing to tissue engineering , 2006, Biotechnology journal.

[22]  H. Sintonen,et al.  Effectiveness of hip or knee replacement surgery in terms of quality-adjusted life years and costs , 2007, Acta orthopaedica.

[23]  Kam Leong,et al.  Designing zonal organization into tissue-engineered cartilage. , 2006, Tissue engineering.

[24]  D. D’Lima,et al.  In vitro model of full‐thickness cartilage defect healing , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  Shyni Varghese,et al.  Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. , 2007, Nature materials.

[26]  Xiaofeng Cui,et al.  Collagen matrix alignment using inkjet printer technology , 2008 .

[27]  T. Boland,et al.  Human microvasculature fabrication using thermal inkjet printing technology. , 2009, Biomaterials.

[28]  P. Gikas,et al.  Current strategies for knee cartilage repair , 2010, International journal of clinical practice.

[29]  T. Boland,et al.  Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells , 2010, Biotechnology and bioengineering.

[30]  Hod Lipson,et al.  Additive manufacturing for in situ repair of osteochondral defects , 2010, Biofabrication.

[31]  Arndt F Schilling,et al.  High amplitude direct compressive strain enhances mechanical properties of scaffold-free tissue-engineered cartilage. , 2011, Tissue engineering. Part A.