Treating mouse skull defects with 3D-printed fatty acid and tricalcium phosphate implants.

Skull surgery, also known as craniectomy, is done to treat trauma or brain diseases and may require the use of an implant to reestablish skull integrity. This study investigates the performance of 3D printed bone implants in a mouse model of craniectomy with the aim of making biodegradable porous implants that can ultimately be fitted to a patient's anatomy. A nonpolymeric thermoplastic bioink composed of fatty acids and ß-tricalcium phosphate was used to 3D print the skull implants. Some of these were sintered to yield pure ß-tricalcium phosphate implants. The performance of nonsintered and sintered implants was then compared in two semi-quantitative murine calvarial defect models using computed tomography, histology, and luciferase activity. Both types of implants were biocompatible, but only sintered implants promoted defect healing, with osseointegration to adjacent bone and the formation of new bone and bone marrow tissue in the implant pores. Luciferase scanning and histology showed that mesenchymal stem cells seeded onto the implants engraft and proliferate on the implants after implantation and contribute to forming bone. The experiments indicate that fatty acid-based 3D printing enables the creation of biocompatible and bone-forming ß-tricalcium phosphate implants.

Simple additive manufacturing of an osteoconductive ceramic using suspension melt extrusion.

OBJECTIVE: Craniofacial bone trauma is a leading reason for surgery at most hospitals. Large pieces of destroyed or resected bone are often replaced with non-resorbable and stock implants, and these are associated with a variety of problems. This paper explores the use of a novel fatty acid/calcium phosphate suspension melt for simple additive manufacturing of ceramic tricalcium phosphate implants. METHODS: A wide variety of non-aqueous liquids were tested to determine the formulation of a storable 3D printable tricalcium phosphate suspension ink, and only fatty acid-based inks were found to work. A heated stearic acid-tricalcium phosphate suspension melt was then 3D printed, carbonized and sintered, yielding implants with controllable macroporosities. Their microstructure, compressive strength and chemical purity were analyzed with electron microscopy, mechanical testing and Raman spectroscopy, respectively. Mesenchymal stem cell culture was used to assess their osteoconductivity as defined by collagen deposition, alkaline phosphatase secretion and de-novo mineralization. RESULTS: After a rapid sintering process, the implants retained their pre-sintering shape with open pores. They possessed clinically relevant mechanical strength and were chemically pure. They supported adhesion of mesenchymal stem cells, and these were able to deposit collagen onto the implants, secrete alkaline phosphatase and further mineralize the ceramic. SIGNIFICANCE: The tricalcium phosphate/fatty acid ink described here and its 3D printing may be sufficiently simple and effective to enable rapid, on-demand and in-hospital fabrication of individualized ceramic implants that allow clinicians to use them for treatment of bone trauma.