Promoting soft and hard tissue repair via immunomodulation by the surface degradation of magnesium implants in vivo

• INTRODUCTION: Magnesium (Mg) is a reactive metallic biomaterial that degrades via surface corrosion upon contact with body fluids. By virtue of its degradation and mechanical properties, Mg implants are currently employed with success to treat musculoskeletal injuries and avoid second-stage surgical removal 1. While these implants are claimed to possess anti-inflammatory properties, this notion contrasts with the initial signs of inflammation observed in the soft tissue of patients treated with Mg implants. This study investigated how the surface degradation of Mg implants in vivo influences the molecular, cellular, and structural events during initial inflammation and subsequent healing of the interfacing soft tissue and bone in comparison to nondegradable titanium (Ti) implants using experimental rat models. METHODS: Rats received disc-shaped implants in their dorsum subcutis or screw-shaped implants in the proximal metaphysis of their tibiae. Implants were manufactured from pure Mg (>99.995% - high purity) or from pure Ti (grade 4). Animals were euthanized after 1, 3, 6, 14, and 28 days of soft tissue implantation, and after 3 and 28 days of bone implantation. Two types of samples were collected: i) Implants only (n = 7-8/group/time-point): for counting and/or gene expression analyses of implant-adherent cells. ii) Implants with peri-implant tissues (n = 5-8/group/time-point): for compositional analysis of the Mg degradation layer in conjunction with the histomorphometry of the fibrous capsule around implants in soft tissues and of osseointegration at the bone–implant interface. Statistical comparisons were run using Kruskal-Wallis and Mann-Whitney tests (p<0.05). RESULTS: Cells adherent to the implant surfaces featured different gene regulation patterns between Mg and Ti groups (Fig. 1). Initially in soft tissue (1–6 d) and bone (3 d), a higher expression of proinflammatory macrophage polarization markers, e.g. inducible nitric oxide synthase (iNos), was shown in Mg versus Ti groups. Afterward, by 28 d, gene expression of both macrophage subtype markers (proinflammatory – iNos, and prohealing – Mannose receptor c1; Mrc1) was comparable between implants, irrespective of their insertion site. Histomorphometry revealed superior bone–implant contact (at 28 d in bone) and thinner fibrous capsule (at 6–28 d in soft tissue) for Mg versus Ti (Fig. 1). The 28 d-degradation layer at the Mg surface was enriched in Ca and P in both soft tissue and bone. CONCLUSIONS: In comparison to Ti implants, both soft tissue and bone responses to Mg implants featured an initial, amplified, yet transient, inflammation marked by the gene activation of the macrophage proinflammatory subtype. Such immunomodulation by the surface degradation of Mg implant promoted more bone deposition, at the bone–implant interface, and less fibrous encapsulation, at the soft tissue–implant interface. REFERENCES: 1. Han et al. Mater Today 2019, 23: 57-71. ACKNOWLEDGEMENTS: Horizon 2020 Marie Skłodowska-Curie Action (No 811226) and Area of Advance Materials/Chalmers and GU Biomaterials. Mg implants were generously provided by Hereon, Geesthacht, Germany.

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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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