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

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 (Sr 2+ ) 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 Sr 2+ 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 mm 3 ) 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.

In-Vivo Degradation Behavior and Osseointegration of 3D Powder-Printed Calcium Magnesium Phosphate Cement Scaffolds

“…For the treatment of many defects, however, the use of precisely fitting and dimensionally stable bone substitutes of defined shape is necessary. Such materials can be produced using 3D powder printing, but have only been investigated in vivo as CPCs [ 40 ] and MPCs [ 41 ] so far. In the present study, two different CMPC scaffolds (Mg225, Mg225d) were therefore produced from the ceramic cement powder Ca 0.75 Mg 2.25 (PO 4 ) 2 using the advantageous powder printing process.…”

“…3D powder-printed scaffolds also have a high microporosity (over 30 vol%), which is created by empty spaces between the powder particles [ 37 ] and promotes the diffusion of nutrients, vascularization of the scaffold and ingrowth of cells [ 38 , 39 ]. In the past, research has been conducted on such customizable 3D powder-printed scaffolds made of CPCs [ 40 ] and MPCs [ 41 ]. The aim of the present study was to develop and investigate rapidly degradable CMPC scaffolds using 3D powder printing, as no in-vivo data could be found in the available literature.…”

Advanced Strategies of Biomimetic Tissue‐Engineered Grafts for Bone Regeneration

“…In general, polymer-based materials especially FDA-approved silk, polycaprolactone (PCL), and poly L lactic acid (PLLA) (common synthetic polymers) are more biocompatible than other materials like ceramics and metals when applied in vivo. [6,16,17] Mechanical Stability: Bone tissues provide structural support for the mechanical action of soft tissues. In turn, bone grafts should have proper mechanical strength for mechanically unstable defects.…”

Regenerative Medicine for Equine Musculoskeletal Diseases

“…Bone physiology, pathology, and repair play an important role in equine medicine, mainly due to the challenges of fracture repair. Although other applications, such as the treatment of bone cysts [ 232 , 233 ], have gained some interest in recent years, most of the equine bone research is focused on fracture repair [ 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 ].…”

“…Best results were evident when the BMP concentration was high, regardless of the cell amount [ 280 ]. With the increasing availability of 3D printers that enable easier handling and mixing of material in different architectural designs, bone replacements are becoming more and more innovative in recent years [ 238 , 240 ]. These advances hold promise for the future possibility to design replacements based on the fracture configuration with a wide variety of materials.…”