In vivo evaluation of additively manufactured multi-layered scaffold for the repair of large osteochondral defects

Maryam Tamaddon; Gordon Blunn; Rongwei Tan; Pan Yang; Xiaodan Sun; Shen-Mao Chen; Jiajun Luo; Ziyu Liu; Ling Wang; Dichen Li; Ricardo Donate; Mario Monzón; Chaozong Liu

doi:10.1007/s42242-021-00177-w

In vivo evaluation of additively manufactured multi-layered scaffold for the repair of large osteochondral defects

Biodes Manuf. 2022;5(3):481-496. doi: 10.1007/s42242-021-00177-w. Epub 2022 Mar 16.

Authors

Maryam Tamaddon¹, Gordon Blunn², Rongwei Tan³, Pan Yang³, Xiaodan Sun⁴, Shen-Mao Chen¹, Jiajun Luo¹, Ziyu Liu¹, Ling Wang⁵, Dichen Li⁵, Ricardo Donate⁶, Mario Monzón⁶, Chaozong Liu¹

Affiliations

¹ Institute of Orthopaedic and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, HA7 4LP UK.
² School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, PO1 2DT UK.
³ Guangdong Engineering Research Center of Implantable Medical Polymer, Shenzhen Lando Biomaterials Co., Ltd., Shenzhen, 518107 China.
⁴ School of Materials Science and Engineering, Tsinghua University, Beijing, 100084 China.
⁵ State Key Laboratory for Manufacturing System Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an, 710054 China.
⁶ Departamento de Ingeniería Mecánica, Grupo de Investigación en Fabricación Integrada y Avanzada, Universidad de Las Palmas de Gran Canaria, Campus Universitario de Tafira s/n, 35017 Las Palmas, Spain.

Abstract

The repair of osteochondral defects is one of the major clinical challenges in orthopaedics. Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects. However, less success has been achieved for the regeneration of large defects, which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue. In this study, we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques. The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen "sandwich" composite system. The microstructure and mechanical properties of the scaffold were examined, and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model. The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen-HAp scaffold, and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage, as demonstrated by hyaline-like cartilage formation. The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group. Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group. The findings showed the safety and efficacy of the cell-free "translation-ready" osteochondral scaffold, which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.

Supplementary information: The online version contains supplementary material available at 10.1007/s42242-021-00177-w.

Keywords: Additive manufacturing; Large animal; Osteochondral scaffold; Porous titanium.