Tough magnesium phosphate-based 3D-printed implants induce bone regeneration in an equine defect model

Nasim Golafshan,Elke Vorndran,Stefan Zaharievski,Harold Brommer,Firoz Babu Kadumudi,Alireza Dolatshahi-Pirouz,Uwe Gbureck,René Van Weeren,Miguel Castilho,Jos Malda

doi:10.1016/j.biomaterials.2020.120302

Abstract

One of the important challenges in bone tissue engineering is the development of biodegradable bone substitutes with appropriate mechanical and biological properties for the treatment of larger defects and those with complex shapes. Recently, magnesium phosphate (MgP) doped with biologically active ions like strontium (Sr2+) have shown to significantly enhance bone formation when compared with the standard calcium phosphate-based ceramics. However, such materials can hardly be shaped into large and complex geometries and more importantly lack the adequate mechanical properties for the treatment of load-bearing bone defects. In this study, we have fabricated bone implants through extrusion assisted three-dimensional (3D) printing of MgP ceramics modified with Sr2+ ions (MgPSr) and a medical-grade polycaprolactone (PCL) polymer phase. MgPSr with 30 wt% PCL (MgPSr-PCL30) allowed the printability of relevant size structures (>780 mm3) at room temperature with an interconnected macroporosity of approximately 40%. The printing resulted in implants with a compressive strength of 4.3 MPa, which were able to support up to 50 cycles of loading without plastic deformation. Notably, MgPSr-PCL30 scaffolds were able to promote in vitro bone formation in medium without the supplementation with osteo-inducing components. In addition, long-term in vivo performance of the 3D printed scaffolds was investigated in an equine tuber coxae model over 6 months. The micro-CT and histological analysis showed that implantation of MgPSr-PCL30 induced bone regeneration, while no bone formation was observed in the empty defects. Overall, the novel polymer-modified MgP ceramic material and extrusion-based 3D printing process presented here greatly improved the shape ability and load-bearing properties of MgP-based ceramics with simultaneous induction of new bone formation.

Highlights

IntroductionGiven the diversity of the treated clinical pictures (ranging from infantile craniofacial anomalies to trauma or cancer), medical progress, and population ageing, a 10% annual increase of bone grafting pro cedures is expected [1]
Given the diversity of the treated clinical pictures, medical progress, and population ageing, a 10% annual increase of bone grafting pro cedures is expected [1]
The 3D printed scaffolds composed of MgPSr and PCL were successfully fabricated by extrusion-based printing at room temperature (Fig. 1A)

Summary

Introduction

Given the diversity of the treated clinical pictures (ranging from infantile craniofacial anomalies to trauma or cancer), medical progress, and population ageing, a 10% annual increase of bone grafting pro cedures is expected [1]. Degradable scaffolds can be either ceramic (e.g. hydroxyapatite [2,3], tri-calcium phosphate [4], or bioglass [5]), polymer-based (e.g. polycaprolactone [6], polylactide-co-glycolide [7]) or composites of both classes of material [8]. Hydroxyapatite [2,3], tri-calcium phosphate [4], or bioglass [5]), polymer-based (e.g. polycaprolactone [6], polylactide-co-glycolide [7]) or composites of both classes of material [8] These materials have been produced by different conventional fabrication methods ranging from porogen leaching [9], freeze-casting [10,11] to casting and gas foaming [12]. The incorporation of osteopromotive ions, like Sr2+, into CaP and MgP ma terials has been shown to induce new bone formation [14,24,25,26]

Methods

Results

Discussion

Conclusion