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Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

ABSTRACT: Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg²⁺ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg²⁺ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg²⁺ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.

SUBMITTER: Ben Amara H

PROVIDER: S-EPMC10024189 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

Ben Amara Heithem H Martinez Diana C DC Shah Furqan A FA Loo Anna Johansson AJ Emanuelsson Lena L Norlindh Birgitta B Willumeit-Römer Regine R Plocinski Tomasz T Swieszkowski Wojciech W Palmquist Anders A Omar Omar O Thomsen Peter P

Bioactive materials 20230316

Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading <i>in situ</i>. Since Mg implants and Mg<sup>2+</sup> have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surf ...[more]

PMID: 36942009

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Project description:Background and Objectives: The influence of the quantity and quality of peri-implant soft tissue on implant health and long-term maintenance is controversial. This consensus aimed to assess the importance of peri-implant soft tissue by analyzing four aspects: the role of keratinized mucosa (KM), the efficacy of specific collagen matrix, the influence of abutment material, and soft-tissue thickness. Materials and Methods: Active members of the Italian Academy of Osseointegration (IAO) participated in the consensus. Four systematic reviews were conducted, and their results were discussed to provide guidelines on the importance of soft tissue around implants. The first review evaluated the effect of KM on soft-tissue health, peri-implant bone loss, and patient-related variables. The second one analyzed if there was a specific type of matrix that provided better results in terms of peri-implant buccal soft-tissue thickness and keratinized mucosa width compared to autogenous soft-tissue graft. The third review evaluated the influence of different abutment materials on the soft tissues, and the fourth assessed the effect of soft-tissue thickness on peri-implant marginal bone loss (MBL). Results and Conclusions: The agreements reached by the assembly were as follows: the presence of supra-periosteal keratinized tissue is considered to favorably influence peri-implant health and aesthetics but had no relation to preventing bone crest resorption unrelated to infection. It facilitates patient cleaning around implants and reduces patient-reported pain. The free gingival graft (FGG) is considered the best in terms of supra-periosteal KM increase. Connective tissue grafts (CTG) perform better than volume-stable collagen matrices to increase soft-tissue thickness. Collagen matrices reduce surgical time and patient morbidity and can give better camouflaging. The influence of abutment material (titanium or zirconia) on MBL remains controversial, and no conclusion could be reached on this issue. Peri-implant soft-tissue health and recession seem not to be influenced by abutment material, but data are limited to zirconia and titanium. Although this systematic review highlighted the absence of a correlation between soft-tissue thickness and MBL, the assembly failed to find a consensus on this issue.

Project description:ObjectivesIn systematically healthy patients with an implant-supported fixed restoration (P), what is the influence of thin (E) as compared to thick (C) peri-implant soft tissues on aesthetic outcomes (O)?MethodsFollowing an a priori protocol, a literature search of six databases was conducted up to August 2020 to identify prospective/retrospective clinical studies on healthy patients with an implant-supported fixed reconstruction. Measurement of the buccal soft tissue thickness and an aesthetic outcome was a prerequisite, and sites presenting with a buccal soft tissue thickness of <2 mm or shimmering of a periodontal probe were categorized as a thin phenotype. After study selection, data extraction, and risk of bias assessment, random-effects meta-analysis of Mean Differences (MD) or Odds Ratios (OR) with their corresponding 95% Confidence Intervals (CI) were conducted, followed by sensitivity analyses and assessment of the quality of evidence.ResultsThirty-four unique studies reporting on 1508 patients with 1606 sites were included (9 randomized controlled trials, one controlled trial, 10 prospective cohort studies, 8 cross-sectional studies, and 6 retrospective cohort studies). The mean difference of the pink aesthetic score (PES) after the follow-up was not significantly different between thin (<2.0 mm) or thick soft tissues (≥2.0 mm) or phenotypes (12 studies; MD = 0.15; [95% CI = -0.24, 0.53]; p = .46). PES changes during the follow-up, however, were significantly in favour of thick soft tissues (≥2.0 mm) or phenotypes (p = .05). An increased mean mucosal thickness was associated with an increased papilla index (5 studies; MD = 0.5; [95% CI = 0.1, 0.3]; p = .002) and an increase in papilla presence (5 studies; OR = 1.6; [95% CI = 1.0, 2.3]; p = .03). Thin soft tissues were associated with more recession, -0.62 mm (4 studies; [95% CI = -1.06, -0.18]; p = .006). Patient-reported outcome measures (patient satisfaction) were in favour of thick soft tissues -2.33 (6 studies; [95% CI = -4.70, 0.04]; p = .05). However, the quality of evidence was very low in all instances due to the inclusion of non-randomized studies, high risk of bias and residual confounding.ConclusionWithin the limitations of the present study (weak study designs and various soft tissue measurements or time-points), it can be concluded that increased soft tissue thickness at implant sites was associated with more favourable aesthetic outcomes.

Project description:ObjectivePeri-implantitis, caused by an inflammatory response to pathogens, is the leading cause of dental implant failure. Poor soft tissue healing surrounding implants - caused by inadequate surface properties - leads to infection, inflammation, and dysregulated keratinocyte and macrophage function. One activated inflammatory response, active around peri-implantitis compared to healthy sites, is the IL-23/IL-17A cytokine axis. Implant surfaces can be synthesized with peptide nanocoatings to present immunomodulatory motifs to target peri-implant keratinocytes to control macrophage polarization and regulate inflammatory axises toward enhancing soft tissue healing.MethodsWe synthesized an IL-23 receptor (IL-23R) noncompetitive antagonist peptide nanocoating using silanization and evaluated keratinocyte secretome changes and macrophage polarization (M1-like "pro-inflammatory" vs. M2-like "pro-regenerative").ResultsIL-23R antagonist peptide nanocoatings were successfully synthesized on titanium, to model dental implant surfaces, and compared to nonfunctional nanocoatings and non-coated titanium. IL-23R antagonist nanocoatings significantly decreased keratinocyte IL-23, and downstream IL-17A, expression compared to controls. This peptide noncompetitive antagonistic function was demonstrated under lipopolysaccharide stimulation. Large scale changes in keratinocyte secretome content, toward a pro-regenerative milieu, were observed from keratinocytes cultured on the IL-23R antagonist nanocoatings compared to controls. Conditioned medium collected from keratinocytes cultured on the IL-23R antagonist nanocoatings polarized macrophages toward a M2-like phenotype, based on increased CD163 and CD206 expression and reduced iNOS expression, compared to controls.SignificanceOur results support development of IL-23R noncompetitive antagonist nanocoatings to reduce the pro-inflammatory IL-23/17A pathway and augment macrophage polarization toward a pro-regenerative phenotype. Immunomodulatory implant surface engineering may promote soft tissue healing and thereby reduce rates of peri-implantitis.

Project description:ObjectivesSoft tissue phenotype modification (STPM) could be performed to maintain peri-implant health. Therefore, the aim of the study was to analyze tissue alteration around implants following soft tissue phenotype modification during implant uncovering surgery.Materials and methodsPatients who had STPM (either pouch roll or modified roll technique) during implant second-stage surgery with at least 12-month follow-up were included. Clinical and radiographic parameters including mucosal tissue thickness (MTT), recession (REC), keratinized mucosa width (KMW), probing pocket depth (PPD), marginal bone loss (MBL), emergence profile, and emergence angle were extracted from 2-week, 2-month, and 12-month visits after second-stage surgery.ResultsTwenty-eight patients with 33 implants that fulfilled the inclusion criteria were included. After soft tissue phenotype modification, at 2 weeks, REC was negatively correlated to mean MTT at mid-buccal site (r = - 0.41, p = 0.018) and borderline correlated at mid-lingual site (r = - 0.343, p = 0.051). Stable KMW was maintained from 2 weeks to 12 months with minimal shrinkage rate (3 ~ 14%). MBL change was limited (0.24 ~ 0.47 mm) after STPM. All implants had shallow PPD (≤ 3 mm) with the absence of bleeding on probing. Emergence angle at the mesial side, however, was significantly correlated to surgical techniques, which indicated pouch roll technique would have 6.96 degrees more than modified roll technique (p = 0.024).ConclusionsSoft tissue phenotype modification, either pouch roll or modified roll technique, during uncovering surgery resulted in favorable clinical outcomes. Thin mucosal tissue thickness and pouch roll technique are the factors related to more recession at 2 weeks. Pouch roll technique could influence the restorative design by having a wide emergence angle at the mesial side.Clinical relevanceModified and pouch roll techniques during uncovering surgery were viable methods to yield favorable peri-implant health, while the preciseness of pouch roll technique was required to avoid mucosal recession and inadequate restorative design.

Dataset Information

Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

Publications

Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues.

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