Preclinical in vivo research of magnesium-based implants for fracture treatment: A systematic review of animal model selection and study design

Degradable magnesium implants are promising for clinical fracture treatment, providing less stress-shielding mechanical support and superior bone-strengthening benefits to traditional materials. The quality of preclinical research is essential for developing Mg implants; however, there are considerable variations in the model selection and study design in published studies, posing challenges for safe and effective clinical translation of lab discoveries. The purpose of this systematic review is to investigate the current progress on in vivo research of Mg implants for fracture treatment, focusing on model selection, Mg materials, implant design, methodological and analyzing techniques, aiming to provide comprehensive guidance for future preclinical research. PubMed and Embase online databases were searched to identify researches investigating Mg implants in animal models of fracture from 1960 to December 2019, using a combination of keywords: magnesium and fracture. Eligible studies were included without language restriction. Data extraction was conducted for qualitative analysis. Meta-analysis was not performed due to extensive heterogeneities among studies. Twenty studies published from 2014 to 2019 were included. Publication information, animal model, methodological quality, implants preparation, and evaluation techniques were extracted. The methodological assessment revealed low to high risk of bias among studies. Both rodent and non-rodent species were selected, and the anatomical sites for inducing fractures included both cranial-facial and limb bones. Pure Mg and alloys with or without surface modification were evaluated, covering implant designs of both intra-medullary and extra-medullary fixation. Radiological and histological evaluations were commonly conducted. Published in vivo evidence confirmed the role of Mg-based implants in promoting fracture healing. However, considering heterogeneity in animal selection, implant preparation, and evaluation methods, there still lacks a standardized reference model. By analyzing the information extracted from included studies, the systematic review may facilitate planning and conducting preclinical research with translational perspective.