In vivo interaction between biodegradable magnesium implants and soft tissue Part II: Kinetics of the cellular response at the host-implant interface

• INTRODUCTION: Regenerative therapies often engage multiple tissues. Soft tissue complications (e.g. dehiscences and infection) may violate successful bone regeneration. Magnesium (Mg)-based degradable implants is a promising treatment alternative for musculoskeletal injuries, avoiding second-stage surgical removal. In several clinical applications, the implant is in contact with both the bone and the overlying soft tissue. Whereas the bone response to Mg implants has been a major research focus, less attention has been paid to the soft tissue response. The present study investigated the spatial and temporal molecular, cellular and structural events taking place at the soft tissue-Mg implant interface after in vivo implantation in an experimental rat model. METHODS: Following approval by the Local Ethical Committee at the University of Gothenburg (Dnr 02437/2018), female Sprague-Dawley rats (n=90) were implanted with discs manufactured from pure magnesium (99.99% - high purity; Mg) or from pure titanium (grade 4; Ti) (herein, employed as a control, possessing biocompatibility properties). Subcutaneous pockets were surgically created in the animal dorsum and were implanted with: 1- Ti; or 2- Mg discs; or 3- left without implants (Sham Ti or Sham Mg). After 1, 3, 6, 14 and 28 days, animals were euthanized, and three types of samples were retrieved: 1-Implants with the adherent cells (n=8/group/time-point): for cell counting and molecular gene expression of the implant-adherent cells. 2-Peri-implant exudate (n=8/group/time-point): for analyses of the number, type, viability, and gene expression of cells in the peri-implant space. 3-Peri-implant tissue with implants (n=8/group/time-point): enabling histological and histomorphometric analyses of soft tissue and fibrous capsule organization around the implant. 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: Cells recruited to the exudates and adherent to the surface of the implants featured different kinetics between Mg and Ti groups. At the surface of Mg implant, the number of adherent cells sharply increased from 1 day to reach a peak at 6 days, thereafter decreasing toward 28 days. The ratio of implant-adherent/exudate cells was significantly higher at Mg vs Ti after 6 days, whereas the reverse was detected after 28 days. RNA extracted from cells from the different compartments revealed good quality, allowing detailed molecular analysis. After 28d, the fibrous capsule around Mg implants was significantly thinner than around Ti. CONCLUSIONS: In comparison to non-degradable Ti controls, soft tissue healing around biodegradable Mg implants is characterized by an early, intense, but yet transient, cellular influx in the immediate vicinity of the implant surface, and, at later stage, with a reduced fibrotic encapsulation. ACKNOWLEDGEMENTS: Mg implants 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 Skodowska-Curie Action No 811226.

Ämnesord

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

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

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