Bone Tissue Interaction With 3d-Printed Titanium Implants in a Bioreactor Testing Machine: A Preclinical Assessment Methodology for New Implant Designs

Abstract

The success of cementless orthopaedic implants relies on bony ingrowth and active bone remodelling. Much research effort is invested to develop implants with controllable surface roughness and internal porous architectures that encourage these biological processes. Evaluation of these implants requires long-term and costly animal studies, which do not always yield the desired outcome requiring iteration. The aim of our study is to develop a cost-effective method to prescreen design parameters prior to animal trials to streamline implant development and reduce live animal testing burden.Ex vivo porcine cancellous bone cylinders (n=6, Ø20×12mm) were extracted from porcine knee joints with a computer-numerically-controlled milling machine under sterile conditions within 4 hours of animal sacrifice. The bone discs were implanted with Ø6×12mm additive manufactured porous titanium implants and were then cultured for 21days. Half underwent static culture in medium (DMEM, 10% FBS, 1% antibiotics) at 37°C and 5% CO2. The rest were cultured in novel high-throughput stacked configuration in a bioreactor that simulated physiological conditions after surgery: the fluid flow and cyclic compression force were set at 10ml/min and 10–150 N (1Hz,5000 cycles/day) respectively. Stains were administered at days 7 and 14. Samples were evaluated with widefield microscopy, scanning electron microscopy (SEM) and with histology.More bone remodelling was observed on the samples cultured within the bioreactor: widefield imaging showed more remodelling at the boundaries between the implant-bone interface, while SEM revealed immature bone tissue integration within the pores of the implant. Histological analysis confirmed these results, with many more trabecular struts with new osteoid formation on the samples cultured dynamically compared to static ones.Ex vivo bone can be used to analyse new implant technologies with lower cost and ethical impact than animal trial. Physiological conditions (load and fluid flow) promoted bone ingrowth and remodelling.