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Investigation of bone reconstruction using an attenuated immunogenicity xenogenic composite scaffold fabricated by 3D printing

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Abstract

Bone is known to have a natural function to heal itself. However, if the bone damage is beyond a critical degree, intervention such as bone grafting may be imperative. In this work, the fabrication of a novel bone scaffold composed of natural bone components and polycaprolactone (PCL) using 3D printing is put forward. α1, 3-galactosyltransferase deficient pigs were used as the donor source of a xenograft. Decellularized porcine bone (DCB) with attenuated immunogenicity was used as the natural component of the scaffold with the aim to promote bone regeneration. The 3D printed DCB-PCL scaffolds combined essential advantages such as uniformity of the interconnected macropores and high porosity and enhanced compressive strength. The biological properties of the DCB-PCL scaffolds were evaluated by studying cell adhesion, viability, alkaline phosphatase activity and osteogenic gene expression of human bone marrow-derived mesenchymal stem cells. The in vitro results demonstrated that the DCB-PCL scaffolds exhibit an enhanced performance in promoting bone differentiation, which is correlated to the DCB content. Furthermore, critical-sized cranial rat defects were used to assess the effect of DCB-PCL scaffolds on bone regeneration in vivo. The results confirm that in comparison with PCL scaffolds, the DCB-PCL scaffolds can significantly improve new bone formation in cranial defects. Thus, the proposed 3D printed DCB-PCL scaffolds emerge as a promising regeneration alternative in the clinical treatment of large bone defects.

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Acknowledgements

The authors acknowledge the financial support from National Natural Science Foundation of China (81601626), Zhejiang Provincial Natural Science of Foundation of China (Y20C070010), start-up funding from Wenzhou Institute, University of Chinese Academy of Sciences (WIUCASQD2019002) and Singapore MOE Tier 1 Grant RG46/18. The authors would also like to acknowledge the Yifan Dai’s lab for providing bone tissue from alpha 1, 3 GT deficient pigs.

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Author notes

  1. Qiongxi Pan, Chenyuan Gao and Yingying Wang have contributed equally to this work.

Authors and Affiliations

  1. School of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang Province, People’s Republic of China

    Qiongxi Pan, Yingying Wang & Huaqiong Li

  2. Engineering Research Center of Clinical Functional Materials and Diagnosis and Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325011, Zhejiang Province, People’s Republic of China

    Qiongxi Pan, Chenyuan Gao, Yili Wang & Huaqiong Li

  3. Key Laboratory of Orthopedics of Zhejiang Province, Department of Orthopedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People’s Republic of China

    Cong Mao & Quan Wang

  4. Medway School of Pharmacy, University of Kent, Medway Campus, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK

    Sophia N. Economidou

  5. CIPER, Centre for Innovation and Process Engineering Research, Kent, ME4 4TB, UK

    Dennis Douroumis

  6. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore

    Feng Wen

  7. School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore

    Lay Poh Tan

Authors
  1. Qiongxi Pan
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  5. Cong Mao
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  8. Dennis Douroumis
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  9. Feng Wen
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  10. Lay Poh Tan
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  11. Huaqiong Li
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Contributions

H.Q. Li and L.P. Tan designed the experiments. Q.X. Pan, C.Y. Gao, Y.Y. Wang and Y.L. Wang performed the experiments. Q.X. Pan and C.Y. Gao drafted the manuscript. C. Mao, Q. Wang, F. Wen, S.N. Economidou and D. Douroumis performed the data analysis. H.Q. Li provided funding for this project and supervised the experiments. All authors edited and approved the final manuscript.

Corresponding authors

Correspondence to Lay Poh Tan or Huaqiong Li.

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Any related research on animal experiments included in this study is in line with ethical requirements.

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Pan, Q., Gao, C., Wang, Y. et al. Investigation of bone reconstruction using an attenuated immunogenicity xenogenic composite scaffold fabricated by 3D printing. Bio-des. Manuf. 3, 396–409 (2020). https://doi.org/10.1007/s42242-020-00086-4

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  • DOI: https://doi.org/10.1007/s42242-020-00086-4

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