Regeneration of segmental defects in metatarsus of sheep with vascularized and customized 3D-printed calcium phosphate scaffolds

Luciano Vidal,Meadhbh Á Brennan,Oskar Hoffmann,Carina Kampleitner,Philippe Rosset,Stéphanie Krissian,Yago Raymond,Pierre Layrolle,Yassine Maazouz,Maria-Pau Ginebra

doi:10.1038/s41598-020-63742-w

Abstract

Although autografts are considered to be the gold standard treatment for reconstruction of large bone defects resulting from trauma or diseases, donor site morbidity and limited availability restrict their use. Successful bone repair also depends on sufficient vascularization and to address this challenge, novel strategies focus on the development of vascularized biomaterial scaffolds. This pilot study aimed to investigate the feasibility of regenerating large bone defects in sheep using 3D-printed customized calcium phosphate scaffolds with or without surgical vascularization. Pre-operative computed tomography scans were performed to visualize the metatarsus and vasculature and to fabricate customized scaffolds and surgical guides by 3D printing. Critical-sized segmental defects created in the mid-diaphyseal region of the metatarsus were either left empty or treated with the 3D scaffold alone or in combination with an axial vascular pedicle. Bone regeneration was evaluated 1, 2 and 3 months post-implantation. After 3 months, the untreated defect remained non-bridged while the 3D scaffold guided bone regeneration. The presence of the vascular pedicle further enhanced bone formation. Histology confirmed bone growth inside the porous 3D scaffolds with or without vascular pedicle inclusion. Taken together, this pilot study demonstrated the feasibility of precised pre-surgical planning and reconstruction of large bone defects with 3D-printed personalized scaffolds.

Highlights

Bone is a dynamic tissue that possesses the intrinsic capacity to heal within 6–8 weeks after immobilization of a fracture
Biomimetic calcium phosphates consisting of calcium-deficient hydroxyapatite (CDHA) that can be manufactured at ambient temperature have been developed and have shown to have enhanced surface area and promote osteogenic differentiation and bone healing compared to their sintered counterparts[15,16]
A computed tomography (CT) angioscan of the metatarsus of sheep was performed to visualize the local vasculature and bone (Fig. 1a). This 3D reconstruction shows that three main blood vessels were present along the metatarsal bone, while the lateral plantar artery was selected for axial vasculature of the 3D scaffolds

Summary

Introduction

Bone is a dynamic tissue that possesses the intrinsic capacity to heal within 6–8 weeks after immobilization of a fracture. 3D printing allows accurate control of construct shape and their interconnected porosity favoring body fluids permeability, cell invasion, vascularization and bone ingrowth, making these 3D scaffolds promising therapeutic alternatives to treat large bone defects[15,17,18,19]. Recent studies have attempted to enhance vascularization by either pre-vascularizing the construct before implantation or by adding angiogenic growth factors such as vascular endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF) during the grafting procedure These approaches showed promising results, novel strategies are required to further enable vascularization, in particular for large bone defects[12,20,21,22]. We hypothesize that the application of a 3D-printed CDHA scaffold with pre-defined shape and interconnected porosity combined with a local and axial vascular pedicle will improve bone regeneration

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Conclusion