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Bio-Design and Manufacturing  2022 Vol.5 No.3 P.481-496

http://doi.org/10.1007/s42242-021-00177-w


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


Author(s):  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

Affiliation(s):  Institute of Orthopaedic and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore HA7 4LP, UK; more

Corresponding email(s):   Chaozong.Liu@ucl.ac.uk

Key Words:  Osteochondral scaffold, Large animal, Additive manufacturing, Porous titanium


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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. In vivo evaluation of additively manufactured multi-layered scaffold for the repair of large osteochondral defects[J]. Journal of Zhejiang University Science D, 2022, 5(3): 481-496.

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author="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",
journal="Journal of Zhejiang University Science D",
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%A Maryam Tamaddon
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%A Rongwei Tan
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%A Xiaodan Sun
%A Shen-Mao Chen
%A Jiajun Luo
%A Ziyu Liu
%A Ling Wang
%A Dichen Li
%A Ricardo Donate
%A Mario Monzón & Chaozong Liu
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A1 - Shen-Mao Chen
A1 - Jiajun Luo
A1 - Ziyu Liu
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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.

伦敦大学学院刘朝宗等 | 用于修复大面积骨软骨缺损的增材制造多层支架的体内评价

本研究论文聚焦用于修复大面积骨软骨缺损的增材制造多层支架的体内评价。骨软骨缺损的修复是骨科的主要临床挑战之一。成熟的骨软骨组织工程方法已显示出早期治疗较小软骨缺陷的潜力。然而,大缺陷的再生成功率较低,这主要是由于关节的机械环境和组织的异质性导致。在这项研究中,我们利用增材制造技术并结合已有的激光烧结和材料挤压技术,开发了一种多层骨软骨支架,以匹配骨软骨组织的天然异质性。该支架基于钛和聚乳酸基质增强的胶原,形成“三明治”的复合结构。我们研究了支架的微观结构和力学性能,并在绵羊髁软骨模型中测试了其在修复大面积骨软骨缺损中的安全性和有效性。通过12 周的体内评价,与胶原蛋白-羟基磷灰石支架相比,多层支架中的骨长入广泛且显著增加,并且实现了稳定的机械固定,为覆盖软骨的愈合提供了有力的支持,可通过透明状软骨的形成来证明。组织学检查显示,多层支架组的再生软骨优于对照组。软骨形成基因如聚集蛋白聚糖和胶原蛋白-II 在支架中增加,高于对照组。研究结果揭示了无细胞“可转化”骨软骨支架的安全性和有效性,该支架有可能用于下一步外科手术治疗大面积骨软骨缺损。

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