Bioactivity and antibacterial effects of zinc-containing bioactive glass on the surface of zirconia abutments

As dental implant treatment is now recognized as a successful option for replacing missing teeth with functional and aesthetic [[1], [2], [3]] results, there is an increased focus on the longevity of dental implants and clinical outcomes. The vertical thickness of peri‑implant soft tissue is important for maintaining the health of peri‑implant tissues and the stability of the surrounding bone over time [[4], [5], [6]]. A minimum thickness of 2 mm is necessary for implants to develop a supracrestal tissue attachment and undergo physiological changes that protect the implants from oral microorganisms [7]. Gingival fibroblasts (GFs) are major components of the connective tissue around implants. The mature peri‑implant connective tissue is rich in collagen fibers but has fewer cells and blood vessels compared to those around natural teeth [8]. Moon et al. reported that connective tissue within 40 µm of implant abutments contains approximately 32 % of the GFs among all components. These GFs play a role in maintaining a proper seal between the soft tissue and the implant-abutment interface [9].

Peri-implant diseases are pathological inflammatory conditions caused by the accumulation of biofilm [10,11]. The consensus report from the Sixth European Workshop on Periodontology indicated that peri‑implant mucositis was observed in approximately 80 % of the subjects who had received implant restorations, and peri‑implantitis was found in 28 % to 56 % of the subjects [12]. The microbial composition at the peri‑implant infection site showed higher levels of periodontal pathogenic bacteria (e.g., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) compared to that of the healthy site [13]. As a host defense against bacterial pathogens, the production of reactive oxygen species (ROS), such as superoxide anion (O2−), peroxide (O2−2), hydrogen peroxide (H2O2), hydroxyl radicals (−OH), and hydroxyl ion (OH−), is an essential pathogenic mechanism [14,15]. High ROS levels have been observed in the inflammatory environment associated with peri‑implantitis [16]. However, higher concentrations of ROS can have destructive effects on cell membranes, phospholipids, organelles, DNA, and nucleotides [17,18]. They degrade collagen and enzymes, inhibit cell migration and proliferation, causing severe cell damage and increased apoptosis [19,20].

Bioactive glasses (BG), first introduced by Hench et al. in 1969 [21], can release calcium and phosphate ions and form a bone-like hydroxyapatite (HA) surface when soaked in physiological environments, enabling osteoblasts to mineralize and attach to the bone [[22], [23]]. Additionally, BG has osteoinductive and osteogenic properties as it promotes the recruitment, proliferation, and differentiation of immature cells [23]. BG improves angiogenesis through its effect on endothelial cells and fibroblasts. The role of BAGs in the release of vascular endothelial growth factor (VEGF) and fibroblast growth factor (bFGF) facilitates the skin wound healing process [24].

Despite the excellent bioactive properties, the major disadvantage of BG are their low mechanical properties. These characteristics typically limit their use to non-load bearing applications. The original composition of BG, which is 45 %SiO2, 24.5 %Na2O, 24.5 %CaO, and 6 %P2O5 by weight, has been modified over time to enhance its physical and biological properties. The incorporation of various elements, including silver (Ag), magnesium (Mg), strontium (Sr), zinc (Zn), aluminum (Al), potassium (K), fluoride (F), and zirconia (Zr), into the composition of BG has garnered significant interest for enhancing its physical properties and biological activities [25].

Zinc (Zn) is an essential trace element that influences bone metabolism, the central nervous system, immune function, and wound healing. Moreover, Zn was found to positively affect collagen formation and angiogenesis [26]. Zn is a vital cofactor for the function of more than 10 % of proteins encoded by the human genome [27,28]. Approximately 300 enzymes require zinc (Zn) for their activity, and around 3000 transcription factors depend on zinc to maintain their structural integrity [29]. It is well known that Zn has good antibacterial activity against viruses, fungi, and both gram-positive and gram-negative bacteria [30]. Additionally, zinc (Zn) has potent anti-inflammatory properties through the regulation of Cu/Zn superoxide dismutase (SOD) activity, which leads to the indirect removal of extracellular reactive oxygen species (ROS) [31]. This, in turn, results in reduced expression of cyclooxygenase-2 and reduced release of prostaglandin E2 [32]. Furthermore, Zn can reduce the activation of nuclear factor-kappa B and upregulate the expression of anti-inflammatory zinc finger proteins, such as A20 and peroxisome proliferator-activated receptor [[33], [34], [35]].

To achieve the functionalization of the implant abutment, a lot of coating (e.g. hydroxyapatite, TiO2, titanium nitride, silver) have been studied [[36], [37], [38], [39]], and scaffolds comprising biopolymers such as gelatin, chitosan, collagen, and Poly-l-Lacticde Acid have also been studied for drug delivery system [[40], [41], [42]]. But no breakthrough to clinical translation have been achieved. Based on the findings previously described, we hypothesized that Zn containing BG can enhance GF function and achieve antibacterial activity on implant abutment surfaces. The present study aimed to investigate the effect of antibacterial effect of Zn containing GB, and the effects on GF, focusing on the cytotoxicity, antioxidant activities, and collagen gene expression levels in these cells to improve the peri‑implant environments.

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