Bone healing around biodegradable Magnesium implants: Differential response between interfacial and near-implant bone in vivo

• INTRODUCTION: By virtue of their mechanical properties and of their degradation, magnesium (Mg)-based osteosynthesis systems are metallic implants that hold the fractured bones while eliminated in situ, thus offering the promise of reduced complications posed by permanent implants. A growing amount of research validated Mg-based implants for bone fixation by providing robust evidence in support of new bone deposition in contact with the interfacial degradation layer. Whereas Mg-degradation products are known to distribute in the implant environment, less attention has been paid to the bone response at distance from the implant interface. The present study investigated the structural, cellular, and molecular events taking place at the bone-Mg implant interface and at distance from it after in vivo implantation in an experimental rat model. METHODS: Following approval by the Local Ethical Committee at the University of Gothenburg (Dnr: 14790/2019), male Sprague-Dawley rats (n=56) were implanted with miniature screws manufactured from pure magnesium (99.99% - high purity; Mg) or from pure titanium (grade 4; Ti) (herein, serving as a control, enabling osseointegration in this model). In each animal, the metaphysis of the left and right tibiae was drilled prior to the insertion of Ti or Mg screws. After 3 and 28 days, animals were euthanized, and two types of samples were retrieved (Fig. 1): 1-Implants and peri-implant bone for quantitative polymerase chain reaction (qPCR) (n=8/group/time-point): were separately collected and allocated for molecular gene expression of the implant-adherent cells and of the cells in the peri-implant space. 2-Peri-implant bone with implants en bloc for paraffin or plastic embedding (n=6/group/time-point): enabling radiographical analyses using micro-computed tomography (micro-CT) and histomorphometrical measurements of the bone at the implant interface and at distance from it. Statistical comparisons were made between experimental groups at each time point and between time-points for each experimental group. (Kruskal-Wallis, Mann-Whitney and Wilcoxon signed-rank tests; p<0.05). RESULTS: While histological observations provided evidence of new bone formation at the vicinity of both Ti and Mg, the bone marrow at distance from the implant-interface featured morphological differences between groups (Fig. 2). At 3 days, the proportion of the interstitial and microvascular area was significantly higher at the expense of the area occupied by the hematopoietic cells in Mg- vs Ti-implanted metaphyses. At 28 days, bone marrow around Mg implants showed significantly higher adiposity in comparison to Ti implants. Yet, no differences in the trabecular bone micro-architecture were detected between biomaterials by micro-CT analysis at distance from the implant-interface. The RNA extracted from cells from the implant surface and from the peri-implant bone revealed good quality, allowing detailed molecular analysis. CONCLUSIONS: In comparison to non-degradable Ti controls, the degradation of Mg implants changes the composition of the peri-implant bone marrow, but yet without alteration of new bone formation at the implant interface. ACKNOWLEDGEMENTS: Mg rods were generously provided by the Helmholtz-Zentrum Hereon, Geesthacht, Germany. This project is part of the European Training Network within the framework of Horizon 2020 Marie Skłodowska-Curie Action No 811226.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomaterials Science (hsv//eng)

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