In situ handheld three‐dimensional bioprinting for cartilage regeneration
Open accessAbstract
Articular cartilage injuries experienced at an early age can lead to the development of osteoarthritis later in life. In situ three-dimensional (3D) printing is an exciting and innovative biofabrication technology that enables the surgeon to deliver tissue-engineering techniques at the time and location of need. We have created a hand-held 3D printing device (biopen) that allows the simultaneous coaxial extrusion of bioscaffold and cultured cells directly into the cartilage defect in vivo in a single-session surgery. This pilot study assessed the ability of the biopen to repair a full-thickness chondral defect and the early outcomes in cartilage regeneration, and compared these results with other treatments in a large animal model. A standardized critical-sized full-thickness chondral defect was created in the weight-bearing surface of the lateral and medial condyles of both femurs of six sheep. Each defect was treated with one of the following treatments: (i) hand-held in situ 3D printed bioscaffold using the biopen (HH group), (ii) preconstructed bench-based printed bioscaffolds (BB group), (iii) microfractures (MF group) or (iv) untreated (control, C group). At 8 weeks after surgery, macroscopic, microscopic and biomechanical tests were performed. Surgical 3D bioprinting was performed in all animals without any intra- or postoperative complication. The HH biopen allowed early cartilage regeneration. The results of this study show that real-time, in vivo bioprinting with cells and scaffold is a feasible means of delivering a regenerative medicine strategy in a large animal model to regenerate articular cartilage.
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The handheld device can be manually operated during surgery or integrated into a robotic arm for more efficient reconstruction.
“Another innovative aspect is that the handheld device can be manually operated during surgical procedures [12] or integrated into a robotic arm for more efficient reconstruction [16, 17].”
From Development of silk microfiber-reinforced bioink for muscle tissue engineering and in situ printing by a handheld 3D printer (2025) · cites this paper as [12]
Handheld printers can print different materials and cell types, making them suitable for multicellular complexity in tissue repair and regeneration.
“Different materials and cell types can be printed making it well-suited to address multicellular complexity in tissue repair and regeneration [11, 12, 14, 15].”
From Development of silk microfiber-reinforced bioink for muscle tissue engineering and in situ printing by a handheld 3D printer (2025) · cites this paper as [12]
Handheld 3D bioprinters offer a potential solution for in situ 3D bioprinting in tissue repair.
“Handheld 3D bioprinters offer a potential solution for implementing in situ 3D bioprinting technology in tissue repair approaches [11–13].”
From Development of silk microfiber-reinforced bioink for muscle tissue engineering and in situ printing by a handheld 3D printer (2025) · cites this paper as [12]
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Cites
A 3D bioprinting system to produce human-scale tissue constructs with structural integrity
Kang, H.-W., Lee, S. J., Ko, I. K., Kengla, C., Yoo, J. J., & Atala, A. (2016) · Nature Biotechnology · doi:10.1038/nbt.3413 · Cited by 2,622 · see citing works
Hunziker, E. B. (2002) · Osteoarthritis and Cartilage · doi:10.1053/joca.2002.0801 · Cited by 1,983 · see citing works
EVALUATION OF CARTILAGE INJURIES AND REPAIR
Brittberg, M., & Winalski, C. S. (2003) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200300002-00008 · Cited by 1,342 · see citing works
Schuurman, W., Levett, P. A., Pot, M. W., van Weeren, P. R., Dhert, W. J. A., Hutmacher, D. W., Melchels, F. P. W., Klein, T. J., & Malda, J. (2013) · Macromolecular Bioscience · doi:10.1002/mabi.201200471 · Cited by 791 · see citing works
Direct Human Cartilage Repair Using Three-Dimensional Bioprinting Technology
Cui, X., Breitenkamp, K., Finn, M. G., Lotz, M., & DʼLima, D. D. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2011.0543 · Cited by 688 · see citing works
Bio-ink properties and printability for extrusion printing living cells
Chung, J. H.-Y., Naficy, S., Yue, Z., Kapsa, R. M. I., Quigley, A. F., Moulton, S. E., & Wallace, G. G. (2013) · Biomaterials Science · doi:10.1039/c3bm00012e · Cited by 612 · see citing works
Self-citationvan den Borne, M. P. J., Raijmakers, N. J. H., Vanlauwe, J., Victor, J. M. K., de Jong, S. N., Bellemans, J., & Saris, D. B. F. (2007) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2007.05.005 · Cited by 555 · see citing works
Korhonen, R. K., Laasanen, M. S., Töyräs, J., Rieppo, J., Hirvonen, J., Helminen, H. J., & Jurvelin, J. S. (2002) · Journal of Biomechanics · doi:10.1016/s0021-9290(02)00052-0 · Cited by 460 · see citing works
Fedorovich, N. E., Schuurman, W., Wijnberg, H. M., Prins, H., van Weeren, P. R., Malda, J., Alblas, J., & Dhert, W. J. A. (2011) · Tissue Engineering Part C Methods · doi:10.1089/ten.tec.2011.0060 · Cited by 402 · see citing works
Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite
Sharma, B., Fermanian, S., Gibson, M., Unterman, S., Herzka, D. A., Cascio, B., Coburn, J., Hui, A. Y., Marcus, N., Gold, G. E., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004838 · Cited by 342 · see citing works
Autologous Osteochondral Grafting in the Knee: Indication, Results, and Reflections
Jakob, R. P., Franz, T., Gautier, E., et al. (2002) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-200208000-00020 · Cited by 297 · see citing works
Evaluation of the reasons for failure of integration during cartilage repair. A review
Khan, I. M., Gilbert, S. J., Singhrao, S. K., Duance, V. C., & Archer, C. W. (2008) · European Cells and Materials · doi:10.22203/ecm.v016a04 · Cited by 279 · see citing works
O’Connell, C. D., Bella, C. D., Thompson, F., Augustine, C., Beirne, S., Cornock, R., Richards, C. J., Chung, J. H.-Y., Gambhir, S., Yue, Z., et al. (2016) · Biofabrication · doi:10.1088/1758-5090/8/1/015019 · Cited by 274 · see citing works
Self-citationRutgers, M., van Pelt, M. J. P., Dhert, W. J. A., Creemers, L. B., & Saris, D. B. F. (2009) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2009.08.009 · Cited by 248 · see citing works
Clinical Cartilage Restoration: Evolution and Overview
Farr, J., Cole, B. J., Dhawan, A., et al. (2011) · Clinical Orthopaedics and Related Research · doi:10.1007/s11999-010-1764-z · Cited by 231 · see citing works
Three-dimensional bioprinting in tissue engineering and regenerative medicine
Gao, G., & Cui, X. (2015) · Biotechnology Letters · doi:10.1007/s10529-015-1975-1 · Cited by 228 · see citing works
Current treatment options for the restoration of articular cartilage.
Gilbert, J. E. (1998) · PubMed · Cited by 162 · see citing works
Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold
Ye, K., Felimban, R. I., Traianedes, K., Moulton, S. E., Wallace, G. G., Chung, J. H.-Y., Quigley, A. F., Choong, P., & Myers, D. E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099410 · Cited by 128 · see citing works
Self-citationTognana, E., Chen, F., Padera, R. F., et al. (2005) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2004.10.015 · Cited by 82 · see citing works
Basic Science and Treatment Options for Articular Cartilage Injuries
Lewis, P. B., McCarty, L. P., Kang, R. W., et al. (2006) · Journal of Orthopaedic and Sports Physical Therapy · doi:10.2519/jospt.2006.2175 · Cited by 71 · see citing works
The Basic Science and Surgical Treatment Options for Articular Cartilage Injuries of the Knee
Tetteh, E. S., Bajaj, S., Ghodadra, N. S., et al. (2012) · Journal of Orthopaedic and Sports Physical Therapy · doi:10.2519/jospt.2012.3673 · Cited by 68 · see citing works
Nasal chondrocytes and fibrin sealant for cartilage tissue engineering
Vinatier, C. S., Gauthier, O., Masson, M., et al. (2008) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31988 · Cited by 63 · see citing works
Deponti, D., Giancamillo, A. D., Gervaso, F., et al. (2013) · Tissue Engineering Part A · doi:10.1089/ten.tea.2013.0171 · Cited by 49 · see citing works
3D Printing and Biofabrication for Load Bearing Tissue Engineering
Jeong, C. G., & Atala, A. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-22345-2_1 · Cited by 35 · see citing works
Stok, K. S., Lisignoli, G., Cristino, S., et al. (2009) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32503 · Cited by 35 · see citing works
Repair of Steps and Gaps in Articular Fracture Models
Bálint, L., Park, S. H., Bellyei, Á., et al. (2005) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000145888.86652.e9 · Cited by 5 · see citing works
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Biofabrication strategies for 3D in vitro models and regenerative medicine
Moroni, L., Burdick, J. A., Highley, C., Lee, S. J., Morimoto, Y., Takeuchi, S., & Yoo, J. J. (2018) · Nature Reviews Materials · doi:10.1038/s41578-018-0006-y · Cited by 753 · see citing works
Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs
Ashammakhi, N., Ahadian, S., Xu, C., Montazerian, H., Ko, H., Nasiri, R., Barros, N., & Khademhosseini, A. (2019) · Materials Today Bio · doi:10.1016/j.mtbio.2019.100008 · Cited by 549 · see citing works
Askari, M., Afzali Naniz, M., Kouhi, M., Saberi, A., Zolfagharian, A., & Bodaghi, M. (2021) · Biomaterials Science · doi:10.1039/d0bm00973c · Cited by 369 · see citing works
Design, printing, and engineering of regenerative biomaterials for personalized bone healthcare
Jia, Z., Xu, X., Zhu, D., & Zheng, Y. (2023) · Progress in Materials Science · doi:10.1016/j.pmatsci.2023.101072 · Cited by 176 · see citing works
Trucco, D., Vannozzi, L., Teblum, E., Telkhozhayeva, M., Nessim, G. D., Affatato, S., Al‐Haddad, H., Lisignoli, G., & Ricotti, L. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202001434 · Cited by 94 · see citing works
Portable hand-held bioprinters promote in situ tissue regeneration
Pazhouhnia, Z., Beheshtizadeh, N., Namini, M. S., & Lotfibakhshaiesh, N. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10307 · Cited by 60 · see citing works
In situ 3D bioprinting: a promising technique in advanced biofabrication strategies
Mahmoudi, Z., Sedighi, M., Jafari, A., Naghieh, S., Stefanek, E., Akbari, M., & Savoji, H. (2023) · Bioprinting · doi:10.1016/j.bprint.2023.e00260 · Cited by 38 · see citing works
Kamaraj, M., Rezayof, O., Barer, A., Kim, H., Moghimi, N., Joshi, A., Dokmeci, M. R., Khademhosseini, A., Alambeigi, F., & John, J. V. (2025) · Biomaterials Advances · doi:10.1016/j.bioadv.2024.214057 · Cited by 17 · see citing works
- Authors
- Di Bella, C., Duchi, S., O'Connell, C. D., Blanchard, R., Augustine, C., Yue, Z., Thompson, F., Richards, C., Beirne, S., Onofrillo, C., Bauquier, S. H., Ryan, S. D., Pivonka, P., Wallace, G. G., & Choong, P. F.
- Affiliations
- Department of Surgery University of Melbourne Melbourne Australia
- The University of Melbourne (AU)
- ARC Centre of Excellence for Electromaterial Science, Intelligent Polymer Research Institute University of Wollongong Wollongong Australia
- University of Wollongong (AU)
- Translational Research and Animal Clinical Trial Study Group (TRACTS), Faculty of Veterinary and Agricultural Sciences University of Melbourne Melbourne Australia
- ORCID
- Venue
- Journal of Tissue Engineering and Regenerative Medicine
- Publisher
- Wiley
- Published
- 2017-08-25
- Volume
- 12
- Issue
- 3
- Pages
- 611-621
- ISSN
- 1932-6254 (ISSN-L)
- 1932-7005
- OpenAlex
- W2614663502
- Cited by
- 313
- References
- 26
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 38 · 2023: 42 · 2022: 44 · 2021: 53 · 2020: 40 · 2019: 36 · 2018: 10 · 2017: 4
- FWCI
- 11.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Tissue Engineering and Regenerative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Arthritis Australia (Zimmer Australia Grant)
- Australian Research Council (CE 140100012)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- articular cartilage regeneration, full-thickness chondral defects, coaxial extrusion, osteoarthritis, sheep model, microfracture, cartilage biomechanics, regenerative medicine
- MeSH terms
- Animals, Biomechanical Phenomena, Cartilage, Articular, Male, Regeneration, Sheep, Tissue Engineering, Mesenchymal Stem Cells, Bioprinting, Printing, Three-Dimensional
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