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

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RESEARCH ARTICLE

Investigation of bone reconstruction using an attenuated immunogenicity xenogenic composite scaffold fabricated by 3D printing Qiongxi Pan1,2 · Chenyuan Gao2 · Yingying Wang1 · Yili Wang2 · Cong Mao3 · Quan Wang3 · Sophia N. Economidou4 · Dennis Douroumis5 · Feng Wen6 · Lay Poh Tan7 · Huaqiong Li1,2 Received: 24 April 2020 / Accepted: 26 June 2020 © Zhejiang University Press 2020

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. Keywords  Polycaprolactone · 3D printing · Decellularized porcine bone · Cranial bone regeneration · Attenuated immunogenicity

Introduction Bone is generally ranked as the second most transplanted tissue worldwide. According to a recently published market report, the global market demand for bone grafts and substitutes was valued at $2.69 billion in 2017 and expected to Qiongxi Pan, Chenyuan Gao and Yingying Wang have contributed equally to this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s4224​2-020-00086​-4) contains supplementary material, which is available to authorized users. * Lay Poh Tan [email protected] * Huaqiong Li [email protected] Extended author information available on the last page of the article

reach the $3.91 billion by 2025 globally, with a compound annual growth rate around 4.8% in the years between 2018 and 2025 [1–3]. Bone transplantation is necessary when the defect is beyond a critical degree and the natural healing function of the tissue does not suffice to restore it. In such cases, bone grafting is the preferred op