3D Bioprinted Integrated Osteochondral Scaffold-Mediated Repair of Articular Cartilage Defects in the Rabbit Knee
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To demonstrate that a 3D-bioprinted integrated osteochondral scaffold can provide improved repair of articular cartilage defects in the rabbit knee compared to that reported for traditional tissue-engineering methods.
Bone marrow mesenchymal stem cells were differentiated into osteoblasts and chondrocytes as seed cells and mixed with the corresponding bone and cartilage scaffold materials. An integrated osteochondral biphasic scaffold was fabricated via 3D-bioprinting technology through successive natural overlays of the printed material and used to repair full-thickness articular cartilage defects in the rabbit knee. Histological and biomechanical assessment of repaired tissue at 6 months post-transplantation showed almost complete repair of injured articular surfaces and presence of hyaline cartilage. A boundary existed between the transition and repair zones. The Wakitani histological score was 5.50 ± 2.07 points; maximum load was 183.11 ± 35.20 N. Repaired cartilage was integrated firmly with the subchondral bone and almost assimilated with surrounding cartilage and bone tissues.
The 3D bioprinted integrated osteochondral scaffold achieved double bionic effects on the scaffold composition and structure, and it is expected to offer a new strategy for articular cartilage repair and regeneration.
KeywordsSodium alginate Hydroxyapatite Bone marrow-derived mesenchymal stem cell 3D bioprinting Articular cartilage defect Scaffold material
This research was supported by the Natural Science Foundation of Zhejiang Province of China (Nos. LY18H180010, LY17H060011, and LY17H280008), grants from the Zhejiang Provincial Medical Science and Technology Plan Project of China (Nos. 2015KYB092, 2017KY307, 2017KY299, 2017KY303, and 2019KY364), and grants from Zhejiang Provincial Traditional Chinese Medicine Science and Technology Plan Project of China (Nos. 2016ZA044, 2015ZA045, and 2018ZA017).
- 2.Gratz, K. R., Wong, V. W., Chen, A. C., Fortier, L. A., Nixon, A. J., & Sah, R. L. (2006). Biomechanical assessment of tissue retrieved after in vivo cartilage defect repair: Tensile modulus of repair tissue and integration with host cartilage. Journal of Biomechanics, 39, 138–146.CrossRefGoogle Scholar
- 4.Biao-Qi, C., Ranjith, K., Ai-Zheng, C., Ding-Zhu, Y., Xiao-Xia, C., Ni-Na, J., et al. (2017). Investigation of silk fibroin nanoparticle-decorated poly(l-lactic acid) composite, scaffolds for osteoblast growth and differentiation. International Journal of Nanomedicine, 12, 1877–1890.CrossRefGoogle Scholar
- 5.Yang, Q., Peng, J., Guo, Q., Huang, J., Zhang, L., Yao, J., et al. (2008). A cartilage EMC-derived 3-D porous acellular matrix scaffold for in vivo cartilage tissue engineering with PKH26-labeled chondrogenic bone marrow-derived mesenchymal stem cells. Biomaterials, 29, 2378–2387.CrossRefGoogle Scholar
- 6.Melissa, L. M., Greet, M., Jessica, R., Pascal, G., Petra, H., Peter, C., et al. (2018). Stem cells for cartilage repair: Preclinical studies and insights in translational animal models and outcome measures. Stem Cells International, 2018, 9079538.Google Scholar
- 7.Harley, B. A., Lynn, A. K., Wissner-Gross, Z., Bonfield, W., Yannas, I. V., & Gibson, L. J. (2010). Design of a multiphase osteochondral scaffold iii: Fabrication of layered scaffolds with continuous interfaces. Journal of Biomedical Materials Research, Part A, 92A, 1078–1093.Google Scholar
- 9.Neary, M., Barron, V., Barry, F., Shannon, F., & Murphy, M. (2018). Cartilage repair in a rabbit model: Development of a novel subchondral defect and assessment of early cartilage repair using rabbit mesenchymal stem cell seeded scaffold. Irish Journal of Medical Science, 183, S249–S250.Google Scholar
- 13.Tritzschiavi, J., Charif, N., Henrionnet, C., De, I. N., Bensoussan, D., Magdalou, J., et al. (2010). Original approach for cartilage tissue engineering with mesenchymal stem cells. BioMedical Materials and Engineering, 20, 167–174.Google Scholar
- 14.Lam, J., Lu, S., Lee, E. J., Trachtenberg, J. E., Meretoja, V. V., Dahlin, R. L., et al. (2014). Osteochondral defect repair using bilayered hydrogels encapsulating both chondrogenically and osteogenically pre-differentiated mesenchymal stem cells in a rabbit model. Osteoarthritis and Cartilage, 22, 1291–1300.CrossRefGoogle Scholar
- 16.Ma, G., Zhao, J. L., Mao, M., Chen, J., & Liu, Y. P. (2016). Scaffold-based delivery of bone marrow mesenchymal stem cell sheet fragments enhances new bone formation in vivo. Journal of Oral and Maxillofacial Surgery: Official Journal of the American Association of Oral and Maxillofacial Surgeons, 75, 92–104.CrossRefGoogle Scholar
- 17.Yin, H., Wang, Y., Sun, Z., Sun, X., Xu, Y., Li, P., et al. (2016). Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles. Acta Biomaterialia, 33, 96–109.CrossRefGoogle Scholar
- 18.Zhang, W. Y., Yang, Y. D., He, C., & Chen, Y. (2004). Isolation culture and esteogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells. Zhejiang Practical Medicine, 9, 393–395.Google Scholar
- 19.Zhang, W. Y., Yang, Y. D., He, C., & Chen, Y. (2004). Experimental studies of osteogenic and chondrogenic potentiality of rabbit bone marrow-derived mesenchymal stem cells. Modern Medicine Health, 20, 2083–2085.Google Scholar
- 24.Filion, T. M., Li, X., Mason-Savas, A., Kreider, J. M., Goldstein, S. A., Ayers, D. C., et al. (2011). Elastomeric osteoconductive synthetic scaffolds with acquired osteoinductivity expedite the repair of critical femoral defects in rats. Tissue Engineering Part A, 17, 503–511.CrossRefGoogle Scholar
- 26.Xue, D., Zheng, Q., Zong, C., Li, Q., Li, H., Qian, S., et al. (2010). Osteochondral repair using porous poly(lactide-co-glycolide)/nano-hydroxyapatite hybrid scaffolds with undifferentiated mesenchymal stem cells in a rat model. Journal of Biomedical Materials Research, Part A, 94A, 259–270.CrossRefGoogle Scholar
- 30.Zhang, W., Lian, Q., Li, D., Wang, K., Jin, Z., Bian, W., et al. (2014). cartilage repair and subchondral bone reconstruction based on three-dimensional printing technique. Chinese Journal of Reparative and Reconstructive Surgery, 28, 318–324.Google Scholar
- 31.Wang, F., Yang, L., Duan, X., Tan, H., & Dai, G. (2008). Study on shape and structure of calcified cartilage zone in normal human knee joint. Chinese Journal of Reparative and Reconstructive Surgery, 27, 524–527.Google Scholar
- 32.Havelka, S., Horn, V., Spohrová, D., & Valouch, P. (1984). The calcified–noncalcified cartilage interface: The tidemark. Acta Biologica Hungarica, 35, 271–279.Google Scholar
- 35.Nosewicz, T. L., Reilingh, M. L., Wolny, M., Dijk, C. N. V., & Schell, H. (2013). Influence of basal support and early loading on bone cartilage healing in press-fitted osteochondral autografts. Knee Surgery, Sports Traumatology, Arthroscopy, 22, 1445–1451.Google Scholar