Bioprinted Constructs Incorporating Mesenchymal Stromal Cells for Osteochondral Repair
DOI:
https://doi.org/10.5281/zenodo.22274928Keywords:
Mesenchymal stromal cells; Bioprinting; Osteochondral repair; Compressive modulus; Cartilage tissue engineeringAbstract
Background: Mesenchymal stromal cells can be printed into both compartments of the osteochondral unit, and the field is
methodologically mature but has no clinical use.
Objective: To assess printed constructs against the mechanical properties of native cartilage and subchondral bone, and against
viability and in vivo data.
Methods: Narrative review of bioprinting studies, mechanical testing reports and large-animal experiments.
Findings: Printed cell-laden constructs measured 5.2 kPa as printed and 42.0 kPa after 56 days of chondrogenic culture, against
400-800 kPa quoted for native cartilage and 13.34 +/- 1.69 GPa for human subchondral bone in twelve cadaveric knees. Fibre
reinforcement raised acellular composites to 405 kPa. Viability clustered near 80-90% but fell to 46.5% at a gel-cement interface.
Conclusions: The evidence supports architecture, not bioink chemistry, as the route to cartilage-level stiffness; it does not show
that a printed construct matches subchondral bone or restores a load-bearing joint surface.
References
Hunziker, E.B. (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis and Cartilage, 10(6): 432-463.
Fedorovich, N.E., Schuurman, W., Wijnberg, H.M., Prins, H.-J., van Weeren, P.R., Malda, J., et al. (2012) Biofabrication of osteochondral tissue equivalents by printing topologically defined, cell-laden hydrogel scaffolds. Tissue Engineering Part C: Methods, 18(1): 33-44.
Groll, J., Burdick, J.A., Cho, D.-W., Derby, B., Gelinsky, M., Heilshorn, S.C., et al. (2019) A definition of bioinks and their distinction from biomaterial inks. Biofabrication, 11(1): 013001.
Ozbolat, I.T., Hospodiuk, M. (2016) Current advances and future perspectives in extrusion-based bioprinting. Biomaterials, 76: 321-343.
Malda, J., Visser, J., Melchels, F.P., Jungst, T., Hennink, W.E., Dhert, W.J.A., et al. (2013) 25th anniversary article: engineering hydrogels for biofabrication. Advanced Materials, 25(36): 5011-5028.
Hinton, T.J., Jallerat, Q., Palchesko, R.N., Park, J.H., Grodzicki, M.S., Shue, H.-J., et al. (2015) Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Science Advances, 1(9): e1500758.
Kesti, M., Muller, M., Becher, J., Schnabelrauch, M., D'Este, M., Eglin, D., et al. (2015) A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation. Acta Biomaterialia, 11: 162-172.
Levato, R., Webb, W.R., Otto, I.A., Mensinga, A., Zhang, Y., van Rijen, M., et al. (2017) The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells. Acta Biomaterialia, 61: 41-53.
Galarraga, J.H., Kwon, M.Y., Burdick, J.A. (2019) 3D bioprinting via an in situ crosslinking technique towards engineering cartilage tissue. Scientific Reports, 9: 19987.
Visser, J., Melchels, F.P.W., Jeon, J.E., van Bussel, E.M., Kimpton, L.S., Byrne, H.M., et al. (2015) Reinforcement of hydrogels using three-dimensionally printed microfibres. Nature Communications, 6: 6933.
Peters, A.E., Akhtar, R., Comerford, E.J., Bates, K.T. (2018) The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint. Scientific Reports, 8: 5931.
Cui, X., Breitenkamp, K., Finn, M.G., Lotz, M., D'Lima, D.D. (2012) Direct human cartilage repair using three-dimensional bioprinting technology. Tissue Engineering Part A, 18(11-12): 1304-1312.
Daly, A.C., Critchley, S.E., Rencsok, E.M., Kelly, D.J. (2016) A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage. Biofabrication, 8(4): 045002.
Markstedt, K., Mantas, A., Tournier, I., Martinez Avila, H., Hagg, D., Gatenholm, P. (2015) 3D bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules, 16(5): 1489-1496.
Costantini, M., Idaszek, J., Szoke, K., Jaroszewicz, J., Dentini, M., Barbetta, A., et al. (2016) 3D bioprinting of BM-MSCs-loaded ECM biomimetic hydrogels for in vitro neocartilage formation. Biofabrication, 8(3): 035002.
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. Biotechnology Journal, 10(10): 1568-1577.
Xu, T., Binder, K.W., Albanna, M.Z., Dice, D., Zhao, W., Yoo, J.J., et al. (2013) Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication, 5(1): 015001.
Bernal, P.N., Delrot, P., Loterie, D., Li, Y., Malda, J., Moser, C., et al. (2019) Volumetric bioprinting of complex living-tissue constructs within seconds. Advanced Materials, 31(42): 1904209.
Gehlen, J., Qiu, W., Schadli, G.N., Muller, R., Qin, X.-H. (2023) Tomographic volumetric bioprinting of heterocellular bone-like tissues in seconds. Acta Biomaterialia, 156: 49-60.
Gruene, M., Deiwick, A., Koch, L., Schlie, S., Unger, C., Hofmann, N., et al. (2011) Laser printing of stem cells for biofabrication of scaffold-free autologous grafts. Tissue Engineering Part C: Methods, 17(1): 79-87.
Kilian, D., Ahlfeld, T., Akkineni, A.R., Bernhardt, A., Gelinsky, M., Lode, A. (2020) 3D bioprinting of osteochondral tissue substitutes - in vitro-chondrogenesis in multi-layered mineralized constructs. Scientific Reports, 10: 8277.
Sun, Y., You, Y., Jiang, W., Wang, B., Wu, Q., Dai, K. (2020) 3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration. Science Advances, 6(37): eaay1422.
Blaeser, A., Duarte Campos, D.F., Puster, U., Richtering, W., Stevens, M.M., Fischer, H. (2016) Controlling shear stress in 3D bioprinting is a key factor to balance printing resolution and stem cell integrity. Advanced Healthcare Materials, 5(3): 326-333.
Rathan, S., Dejob, L., Schipani, R., Haffner, B., Mobius, M.E., Kelly, D.J. (2019) Fiber reinforced cartilage ECM functionalized bioinks for functional cartilage tissue engineering. Advanced Healthcare Materials, 8(7): 1801501.
Diloksumpan, P., de Ruijter, M., Castilho, M., Gbureck, U., Vermonden, T., van Weeren, P.R., et al. (2020) Combining multi-scale 3D printing technologies to engineer reinforced hydrogel-ceramic interfaces. Biofabrication, 12(2): 025014.
Mouser, V.H.M., Melchels, F.P.W., Visser, J., Dhert, W.J.A., Gawlitta, D., Malda, J. (2016) Yield stress determines bioprintability of hydrogels based on gelatin-methacryloyl and gellan gum for cartilage bioprinting. Biofabrication, 8(3): 035003.
Chameettachal, S., Midha, S., Ghosh, S. (2016) Regulation of chondrogenesis and hypertrophy in silk fibroin-gelatin-based 3D bioprinted constructs. ACS Biomaterials Science & Engineering, 2(9): 1450-1463.
Idaszek, J., Costantini, M., Karlsen, T.A., Jaroszewicz, J., Colosi, C., Testa, S., et al. (2019) 3D bioprinting of hydrogel constructs with cell and material gradients for the regeneration of full-thickness chondral defect using a microfluidic printing head. Biofabrication, 11(4): 044101.
Di Bella, C., Duchi, S., O'Connell, C.D., Blanchard, R., Augustine, C., Yue, Z., et al. (2018) In situ handheld three-dimensional bioprinting for cartilage regeneration. Journal of Tissue Engineering and Regenerative Medicine, 12(3): 611-621.
Critchley, S., Sheehy, E.J., Cunniffe, G., Diaz-Payno, P., Carroll, S.F., Jeon, O., et al. (2020) 3D printing of fibre-reinforced cartilaginous templates for the regeneration of osteochondral defects. Acta Biomaterialia, 113: 130-143.
Mancini, I.A.D., Schmidt, S., Brommer, H., Pouran, B., Schafer, S., Tessmar, J., et al. (2020) A composite hydrogel-3D printed thermoplast osteochondral anchor as example for a zonal approach to cartilage repair: in vivo performance in a long-term equine model. Biofabrication, 12(3): 035028.
Shim, J.-H., Jang, K.-M., Hahn, S.K., Park, J.Y., Jung, H., Oh, K., et al. (2016) Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. Biofabrication, 8(1): 014102.
Athanasiou, K.A., Rosenwasser, M.P., Buckwalter, J.A., Malinin, T.I., Mow, V.C. (1991) Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. Journal of Orthopaedic Research, 9(3): 330-340.
Francis, S.L., Di Bella, C., Wallace, G.G., Choong, P.F.M. (2018) Cartilage tissue engineering using stem cells and bioprinting technology - barriers to clinical translation. Frontiers in Surgery, 5: 70.
