The effects of keratin-coated titanium on osteoblast function and bone regeneration.

Wool derived keratin, due to its demonstrated ability to promote bone formation, has been suggested as a potential bioactive material for implant surfaces. The aim of this study was to assess the effects of keratin-coated titanium on osteoblast functionin vitroand bone healingin vivo. Keratin-coated titanium surfaces were fabricated via solvent casting and molecular grafting. The effect of these surfaces on the attachment, osteogenic gene, and osteogenic protein expression of MG-63 osteoblast-like cells were quantifiedin vitro. The effect of these keratin-modified surfaces on bone healing over three weeks using an intraosseous calvaria defect was assessed in rodents. Keratin coating did not affect MG-63 proliferation or viability, but enhanced osteopontin, osteocalcin and bone morphogenetic expressionin vitro. Histological analysis of recovered calvaria specimens showed osseous defects covered with keratin-coated titanium had a higher percentage of new bone area two weeks after implantation compared to that in defects covered with titanium alone. The keratin-coated surfaces were biocompatible and stimulated osteogenic expression in adherent MG-63 osteoblasts. Furthermore, a pilot preclinical study in rodents suggested keratin may stimulate earlier intraosseous calvaria bone healing.

The mechanical properties of 3D printed denture base resin incorporating essential oil microcapsules.

Purpose: The aim of this study was to investigate the mechanical properties of three-dimensional (3D) printed denture base resin incorporating microcapsules containing plant essential oils. Materials and Methods: Denture base specimens containing up to 3% w/v essential oil microcapsule powders (MCPs), i.e., eucalyptus, geranium, lavender, menthol, and tea tree, in two resins (Detax and NextDent 3D+) were 3D printed using two printers (Asiga and NextDent 5100). The dispersion and interaction of the MCPs in the resin were assessed by SEM while the mechanical properties of the incorporated denture base including flexural strength (MPa), flexural modulus (MPa), Vickers hardness (VHN), and surface roughness (Ra) were also subsequently evaluated. Statistical analysis of any differences in mean values was determined using a two-way ANOVA with Tukey's post hoc testing (α = .05). Results: The spherical shape of the MCPs was maintained during the mixing and polymerization/printing process. However, the Detax-Asiga group showed significant agglomeration of the MCPs even at the lowest MCP concentration levels (0.5% w/v). Overall, as the microcapsule concentration increased, the mean flexural strength decreased, though the menthol MCP groups remained compliant with the ISO standard. The flexural modulus and harness remained relatively unchanged, and the flexural modulus complied with the ISO standard regardless of the MCP concentration. Surface roughness increased with the addition of the MCPs but also remained below that required for clinical acceptance. Conclusion: Incorporation of microencapsulated plant essential oils into 3D printed denture base resin was successfully achieved. While incorporation negatively influenced flexural strength and surface roughness, little effect on flexural modulus and Vickers hardness was demonstrated.

Medication-related osteonecrosis of the jaw: A disease of significant importance for older patients.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is clinically defined as a non-healing jawbone ulcerative-necrotic lesion appearing after dental therapy or minor trauma in patients treated previously with anti-resorptive, anti-angiogenic or immunomodulators. Older patients with osteoporosis and cancer receive these pharmacological agents regularly. As these patients are long-term survivors, efficient treatment is of paramount importance for their quality of life. METHODS: Literature searches via PubMed were conducted to identify relevant MRONJ studies. Basic information on MRONJ classification, clinical features, and pathosphysiology is presented herein as well as various clinical studies dealing with MRONJ in patients with osteoporosis and cancer. Lastly, we discuss current managment of patients and new trends in treatment of MRONJ. RESULTS: Although close follow-up and local hygiene have been advocated by some authors, severe forms of MRONJ are not responsive to conservative therapy. At present, there is no "gold standard" therapy for this condition. However, as the physiopathological basis of MRONJ is represented by the anti-angiogenic action of various pharmacological agents, new methods to increase and promote local angiogenesis and vascularization have recently been successfully tested in vitro, limited preclinical studies, and in a pilot clinical study. CONCLUSIONS: It appears that the best method implies application on the lesion of endothelial progenitor cells as well as pro-angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and other related molecules. More recently, scaffolds in which these factors have been incorporated have shown positive results in limited trials. However, these studies must be replicated to include a large number of cases before any official therapeutic protocol is adopted.

The Effect of Titanium Surface Topography on Adherent Macrophage Integrin and Cytokine Expression.

Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling, as opposed to persistent inflammation and scar tissue formation. This study examined the effects of titanium surface modification on integrin expression and concurrent cytokine secretion by adherent macrophages in vitro in an attempt to delineate the molecular events involved in biomaterial-mediated immunomodulation. Non-polarised (M0) and inflammatory polarised (M1) macrophages were cultured on a relatively smooth (machined) titanium surface and two proprietary modified rough titanium surfaces (blasted and fluoride-modified) for 24 h. The physiochemical characteristics of the titanium surfaces were assessed by microscopy and profilometry, while macrophage integrin expression and cytokine secretion were determined using PCR and ELISA, respectively. After 24 h adhesion onto titanium, integrin α1 expression was downregulated in both M0 and M1 cells on all titanium surfaces. Expression of integrins α2, αM, ß1 and ß2 increased in M0 cells cultured on the machined surface only, whereas in M1 cells, expression of integrins α2, αM and ß1 all increased with culture on both the machined and rough titanium surfaces. These results correlated with a cytokine secretory response whereby levels of IL-1ß, IL-31 and TNF-α increased significantly in M1 cells cultured on the titanium surfaces. These results show that adherent inflammatory macrophages interact with titanium in a surface-dependent manner such that increased levels of inflammatory cytokines IL-1ß, TNF-α and IL-31 secreted by M1 cells were associated with higher expression of integrins α2, αM and ß1.

Overview of incorporation of inorganic antimicrobial materials in denture base resin: A scoping review.

STATEMENT OF PROBLEM: Dental hygiene for institutionalized patients and recurring Candida-associated denture stomatitis remain problematic because of a patient's limited dexterity or inability to eliminate Candida from denture surfaces. Although there has been extensive research into antimicrobial modification of denture base resins with inorganic materials, scoping reviews of the literature to identify knowledge gaps or efficacy of inorganic antimicrobial materials in denture base resins are lacking. PURPOSE: The purpose of this scoping review was to provide a synopsis of the efficacy of the major classes of inorganic antimicrobial materials currently incorporated into denture base resins. MATERIAL AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews was applied. Four electronic databases, including Embase, PubMed, Web of Science, and Google Scholar, were accessed for articles in the English language, up to February 2019, without restrictions on the date of publication. RESULTS: From the 53 articles selected, 25 distinguishable inorganic materials were found and divided into 3 subgroups. Forty-three articles evaluated nanomaterials, where mostly silver ion nanoparticles and/or titanium dioxide nanoparticles were incorporated into denture base resins. Fourteen articles examined antimicrobial drugs and medications, including azole group medications, amphotericin-B, Bactekiller, chlorhexidine, Novaron, and Zeomic. Two articles classified as others explored hydroxyapatite- and fiber-incorporated denture base resins. CONCLUSIONS: Although nanotechnology and antimicrobial medications or drugs have been successfully used to reduce Candida-associated denture stomatitis, long-term solutions are still lacking, and their disadvantages continue to outweigh their advantages.

Titanium Implant Surface Effects on Adherent Macrophage Phenotype: A Systematic Review.

Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to persistent inflammation and scar tissue formation. As such, the controlled activation of macrophages and modulation of their phenotype through implant surface modification has emerged as a key therapeutic strategy. METHODS: Online databases were searched for in vitro studies between January 1991 and June 2020 which examined the effect of titanium implant surface topography on the adherent macrophage phenotype at either the gene or protein level. RESULTS: Thirty-nine studies were subsequently included for review. Although there was significant heterogeneity between studies, treatment of titanium surfaces increased the surface roughness or hydrophilicity, and hence increased macrophage attachment but decreased cell spreading. Physical coating of the titanium surface also tended to promote the formation of cell clusters. Titanium and titanium-zirconium alloy with a micro- or nano-scale rough topography combined with a hydrophilic surface chemistry were the most effective surfaces for inducing an anti-inflammatory phenotype in adherent macrophages, as indicated by significant changes in cytokine gene expression and or cytokine secretion profiles. CONCLUSIONS: The published data support the hypothesis that incorporation of specific topographical and physiochemical surface modifications to titanium can modulate the phenotypic response of adherent macrophages.

Local delivery of hydrogel encapsulated vascular endothelial growth factor for the prevention of medication-related osteonecrosis of the jaw.

The anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiologic factors in the development of medication-related osteonecrosis of the jaw (MRONJ), a severe debilitating condition with limited treatment options. This study evaluated the potential of a gelatine-hyaluronic acid hydrogel loaded with the angiogenic growth factor, vascular endothelial growth factor (VEGF), as a local delivery system to aid in maintaining vascularization in a bisphosphonate-treated (Zoledronic Acid) rodent maxillary extraction defect. Healing was assessed four weeks after implantation of the VEGF-hydrogel into extraction sockets. Gross examination and histological assessment showed that total osteonecrosis and inflammatory infiltrate was significantly reduced in the presence of VEGF. Also, total vascularity and specifically neovascularization, was significantly improved in animals that received VEGF hydrogel. Gene expression of vascular, inflammatory and bone specific markers within the defect area were also significantly altered in the presence of VEGF. Furthermore, plasma cytokine levels were assessed to determine the systemic effect of locally delivered VEGF and showed similar outcomes. In conclusion, the use of locally delivered VEGF within healing extraction sockets assists bone healing and prevents MRONJ via a pro-angiogenic and immunomodulatory mechanism.

Fluorescence characteristics of E. faecalis in dentine following treatment with oxidizing endodontic irrigants.

INTRODUCTION: This study aimed to assess changes in the fluorescence characteristics of Enterococcus faecalis in human dentine over a period of 24 h following treatment with endodontic irrigants. METHOD: Sterilised, non-functional extracted third molars were embedded in acrylic resin and uniformly sectioned into 2 mm thick dentine sections. After the removal of smear layer, the dentine sections were inoculated with E. faecalis and cultured for 7 days. The infected dentine sections were subsequently treated with different concentrations of sodium hypochlorite (NaOCl) and hydrogen peroxide (H2O2). Bacterial fluorescence readings were assessed at different time points using a calibrated laser device. All data were assessed for normality (Kolmogorov Smirnoff test) and analysed using ANOVA with Bonferroni post-hoc tests. RESULTS: Fluorescence readings were quenched when E. faecalis infected human dentine sections were treated with oxidizing irrigants in vitro. Throughout a 24-hour period, fluorescence recovered in part but did not return to baseline level. CONCLUSION: The fluorescence quenching effect of these oxidizing agents needs to be considered when using laser fluorescence in assessing the quality of root canal debridement or disinfection.

Enamel matrix derivative promotes new bone formation in xenograft assisted maxillary anterior ridge preservation-A randomized controlled clinical trial.

OBJECTIVES: To compare the effectiveness of deproteinized bovine bone mineral with 10% collagen alone (DBBMC) or with enamel matrix derivative (DBBMC-EMD) in ridge preservation. METHODS: 42 maxillary anterior teeth were extracted and received either a DBBMC (control) or DBBMC-EMD (test) treatment protocol. CBCT taken before and 4 months after the extraction procedure was used to measure changes in alveolar ridge width (RW), buccal bone height (BH) and palatal bone height (PH). Bone cores were harvested during implant osteotomy preparation, and the samples processed histomorphometrically to assess the fraction of new bone (%NB), residual graft (%RG) and soft tissue matrix (%STM). RESULTS: Overall, both treatment groups showed significant reductions in mean RW from baseline to 4 months after extraction, but no significant change in either mean BH or PH over this time. When CBCT measurements were analysed according to the initial thickness of the buccal wall (BT < 1 mm vs. BT ≥ 1 mm), significant reductions in all ridge dimensions (RW, BH and PH) were noted in the <1 mm BT group. Histomorphometrically, the DBBMC-EMD test group showed significantly increased new bone formation (%NB): (control = 16.5 ± 6.9% cf.; test = 45.1 ± 8.8%) with less residual graft (%RG): (control = 36.8 ± 8.8% cf.; test = 20.3 ± 7.2%) compared to the DBBMC control group. CONCLUSIONS: Both DBBMC alone and DBBMC-EMD treated sites 4 months after extraction lost RW but showed no significant change in BH or PH. Irrespective of treatment, maxillary anterior teeth with thick initial buccal walls (≥1 mm) exhibited less alveolar ridge reduction 4 months after treatment. The addition of EMD to DBBMC resulted in more new bone formation in the test group.

Incorporation of antimicrobial agents in denture base resin: A systematic review.

STATEMENT OF PROBLEM: Denture base resins (DBRs), such as polymethyl methacrylate, are commonly used in the fabrication of removable dentures because of their physical, mechanical, and esthetic properties. However, the denture base acts as a substrate for microorganism adherence and biofilm formation, which may lead to denture stomatitis and be further complicated by fungal infections, of especial importance with geriatric and immunosuppressed patients. Therefore, methods to enhance the antimicrobial property of DBRs will be beneficial. PURPOSE: The purpose of this systematic review was to evaluate the literature on the antimicrobial activity of DBRs incorporating antimicrobial agents or materials. MATERIAL AND METHODS: A search of English peer-reviewed literature up to February 2019 reporting on antimicrobial activity of DBRs with respect to antimicrobial agents or materials, antimicrobial test effects and methods, and conclusion or knowledge gaps was conducted by using Embase, Google Scholar, PubMed, and Web of Science databases. Search terms included denture base resin and antibacterial, denture base resin and antifungal, and denture base resin and antimicrobial. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied for subsequent data analysis. RESULTS: Of 2536 identified articles, 28 met the inclusion criteria for the systematic review. Antimicrobial materials were divided into 3 groups: antimicrobial monomer or copolymer, phytochemical or phytomedical components, and other compounds. Strategies on how to incorporate these substances into DBRs and their impact on the reduction and prevention of the growth of microorganisms were identified. CONCLUSIONS: Although many efforts have been made to improve the antimicrobial ability of DBRs, this systematic review found that the effectiveness of incorporating of antimicrobial agents into DBRs has not been demonstrated conclusively.

Re-establishment of macrophage homeostasis by titanium surface modification in type II diabetes promotes osseous healing.

Titanium surface mediated immunomodulation may address compromised post-implantation bone healing in diabetes mellitus. To assess in vitro phenotypic changes, M1 and M2 polarised Type 2 diabetic rat (Goto Kakizaki, GK) macrophages were cultured on micro-rough (SLA) or hydrophilic nanostructured SLA (modSLA) titanium. The in vivo effects of the SLA and modSLA surfaces on macrophage phenotype, wound-associated protein expression and bone formation were investigated using a critical-sized calvarial defect model. Compared to healthy macrophages, GK M2 macrophage function was compromised, secreting significantly lower levels of the anti-inflammatory cytokine IL-10. The modSLA surface attenuated the pro-inflammatory cellular environment, reducing pro-inflammatory cytokine production and promoting M2 macrophage phenotype differentiation. ModSLA also suppressed gene expression associated with macrophage multinucleation and giant cell formation and stimulated pro-osteogenic genes in co-cultured osteoblasts. In vivo, modSLA enhanced osteogenesis compared to SLA in GK rats. During early healing, proteomic analysis of both surface adherent and wound exudate material showed that modSLA promoted an immunomodulatory pro-reparative environment. The modSLA surface therefore successfully compensated for the compromised M2 macrophage function in Type 2 diabetes by attenuating the pro-inflammatory response and promoting M2 macrophage activity, thus restoring macrophage homeostasis and resulting in a cellular environment favourable for enhanced osseous healing.

In vivo bone regeneration assessment of offset and gradient melt electrowritten (MEW) PCL scaffolds.

BACKGROUND: Biomaterial-based bone tissue engineering represents a promising solution to overcome reduced residual bone volume. It has been previously demonstrated that gradient and offset architectures of three-dimensional melt electrowritten poly-caprolactone (PCL) scaffolds could successfully direct osteoblast cells differentiation toward an osteogenic lineage, resulting in mineralization. The aim of this study was therefore to evaluate the in vivo osteoconductive capacity of PCL scaffolds with these different architectures. METHODS: Five different calcium phosphate (CaP) coated melt electrowritten PCL pore sized scaffolds: 250 µm and 500 µm, 500 µm with 50% fibre offset (offset.50.50), tri layer gradient 250-500-750 µm (grad.250top) and 750-500-250 µm (grad.750top) were implanted into rodent critical-sized calvarial defects. Empty defects were used as a control. After 4 and 8 weeks of healing, the new bone was assessed by micro-computed tomography and immunohistochemistry. RESULTS: Significantly more newly formed bone was shown in the grad.250top scaffold 8 weeks post-implantation. Histological investigation also showed that soft tissue was replaced with newly formed bone and fully covered the grad.250top scaffold. While, the bone healing did not happen completely in the 250 µm, offset.50.50 scaffolds and blank calvaria defects following 8 weeks of implantation. Immunohistochemical analysis showed the expression of osteogenic markers was present in all scaffold groups at both time points. The mineralization marker Osteocalcin was detected with the highest intensity in the grad.250top and 500 µm scaffolds. Moreover, the expression of the endothelial markers showed that robust angiogenesis was involved in the repair process. CONCLUSIONS: These results suggest that the gradient pore size structure provides superior conditions for bone regeneration.

Oxidising agents and its effect on human dentine fluorescence diagnostic measurements.

BACKGROUND: The ability to determine the effectiveness of root canal disinfection in real-time prior to the final root filling could significantly influence the management and treatment outcomes of root canal therapy. Laser fluorescence devices can detect bacterial fluorescence in real-time, however since quenching of fluorescence is a possible confounding factor, this study explored the effects of oxidising endodontic irrigants on laser fluorescence in dentine. METHODS: A total of 78 transverse 2 mm thick sections were prepared from the crowns of sterilised extracted non-functional third molars that had been embedded in acrylic resin. The dentine sections where then treated with different concentrations of sodium hypochlorite and hydrogen peroxide, with or without further rinsing with distilled water wash. Fluorescence values were recorded over 24 h using the DIAGNOdent laser fluorescence device. RESULTS: Both sodium hypochlorite and hydrogen peroxide cause quenching of fluorescence readings of human dentine, with reductions of 30-60% in fluorescence readings. The quenching effect occurred quickly, and recovery to baseline readings took from 1 h to 24 h. Rinsing with water reduced but did not eliminate the quenching effect. CONCLUSION: The use of laser fluorescence to reliably detect root canal bacteria porphyrins in real-time could significantly influence the management of teeth needing root canal therapy. This study highlighted the quenching effects of some root canal irrigants on human teeth root dentine, a variable that should be considered and controlled prior to using lasers to assist in assessing root canal sterility.

Silver Nanoparticles at Biocompatible Dosage Synergistically Increases Bacterial Susceptibility to Antibiotics.

Antibiotics used to treat bacterial infections can become ineffective over time or result in the emergence of antibiotic resistant pathogens. With the advent of nanotechnology, silver nanoparticles (AgNPs) have gained significant attention as a therapeutic agent due to the well-known antimicrobial properties of silver. However, there are concerns and limited literature on the potential cytotoxicity of nanoparticles at effective antimicrobial concentrations. AgNPs prepared from silver nitrate with glucose reduction were characterized by surface plasmon resonance, dynamic light scattering, zeta potential analysis and transmission electron microscopy. The cytotoxicity of AgNPs towards human gingival fibroblasts over 7 days was determined using cell proliferation assays and confocal microscopy. AgNP MIC and antibacterial effects alone and in combination with 11 antibiotics were determined against a panel of nine microbial species including gram-positive and gram-negative bacterial species. AgNPs concentrations ≤ 1 µg/mL were non-cytotoxic but also showed no antibacterial effects. However, when combined with each of eleven antibiotics, the biocompatible concentration of AgNPs (1 µg/mL) resulted in significant inhibition of bacterial growth for multiple bacterial species that were resistant to either the antibiotics or AgNPs alone. This study presents a promising strategy with further testing in vivo, to develop novel antimicrobial agents and strategies to confront emerging antimicrobial resistance.

Impact of non-surgical periodontal treatment on salivary expression of cytokines related to bone metabolism.

We aimed to evaluate the impact of non-surgical periodontal treatment on the salivary expression of leptin, TNF-α, sclerostin, parathyroid hormone, osteoprotegerin, osteopontin, osteocalcin, IL-6, IL-1ß and fibroblast growth factor 23 in patients with chronic periodontitis after 1 year of follow-up. Fifteen patients with chronic periodontitis (56.0 ± SD 9.6 years) and 15 subjects with gingivitis (39.7 ± SD 4.4 years) were included in the study. Clinical periodontal parameters, such as probing pocket depth (PPD), clinical attachment level (CAL), % of plaque and bleeding on probing (BOP) were evaluated, and non-stimulated whole saliva was collected from all patients before periodontal treatment and after 1 year of follow-up. A bead-based multiplex assay measured cytokines. In the chronic periodontitis group, periodontal treatment significantly improved clinical parameters and reduced the salivary levels of IL-1ß, leptin and TNF-α (p = 0.002, 0.007 and 0.015, respectively). In the gingivitis group, there were also significant improvements in the mean patient %BOP, % Plaque, CAL and PPD. However, there were no significant changes in the cytokine's salivary levels. In conclusion, chronic periodontitis patients showed a significant reduction in the salivary levels of leptin, TNF-α and IL-1ß 1 year after periodontal treatment and a significant improvement in their clinical periodontal parameters suggesting that periodontal treatment alone can downregulate important cytokines associated with bone metabolism.

Role of offset and gradient architectures of 3-D melt electrowritten scaffold on differentiation and mineralization of osteoblasts.

BACKGROUND: Cell-scaffold based therapies have the potential to offer an efficient osseous regenerative treatment and PCL has been commonly used as a scaffold, however its effectiveness is limited by poor cellular retention properties. This may be improved through a porous scaffold structure with efficient pore arrangement to increase cell entrapment. To facilitate this, melt electrowriting (MEW) has been developed as a technique able to fabricate cell-supporting scaffolds with precise micro pore sizes via predictable fibre deposition. The effect of the scaffold's architecture on cellular gene expression however has not been fully elucidated. METHODS: The design and fabrication of three different uniform pore structures (250, 500 and 750 µm), as well as two offset scaffolds with different layout of fibres (30 and 50%) and one complex scaffold with three gradient pore sizes of 250-500 - 750 µm, was performed by using MEW. Calcium phosphate modification was applied to enhance the PCL scaffold hydrophilicity and bone inductivity prior to seeding with osteoblasts which were then maintained in culture for up to 30 days. Over this time, osteoblast cell morphology, matrix mineralisation, osteogenic gene expression and collagen production were assessed. RESULTS: The in vitro findings revealed that the gradient scaffold significantly increased alkaline phosphatase activity in the attached osteoblasts while matrix mineralization was higher in the 50% offset scaffolds. The expression of osteocalcin and osteopontin genes were also upregulated compared to other osteogenic genes following 30 days culture, particularly in offset and gradient scaffold structures. Immunostaining showed significant expression of osteocalcin in offset and gradient scaffold structures. CONCLUSIONS: This study demonstrated that the heterogenous pore sizes in gradient and fibre offset PCL scaffolds prepared using MEW significantly improved the osteogenic potential of osteoblasts and hence may provide superior outcomes in bone regeneration applications.

Subepithelial connective tissue graft with or without enamel matrix derivative for the treatment of multiple Class III-IV recessions in lower anterior teeth: A 3-year randomized clinical trial.

BACKGROUND: This study compared clinical and patient-centered outcomes of subepithelial connective tissue graft (CTG) with and without enamel matrix derivative (EMD) in the treatment of multiple Class III-IV Miller periodontal recession (REC) defects on mandibular anterior teeth. METHODS: This randomized clinical study evaluated 41 patients at 3 years follow-up. One hundred and fifty-six teeth were divided into two groups: test (CTG-EMD, 79 teeth) and control (CTG only, 77 teeth). Clinical REC, keratinized tissue (KT) width, percentage of root coverage, patient-centered outcomes were compared between the two groups. RESULTS: At 36 months follow-up, patient level analysis showed that REC in the test group reduced significantly (5.71 ± 0.58 mm to 1.57 ± 0.85 mm) compared with the control group (5.94 ± 0.46 mm to 2.51 ± 0.62 mm) (P < 0.001), while KT width increased in the test group (1.51 ± 0.26 mm to 4.18 ± 0.34 mm) and was significantly greater than the control group (1.65 ± 0.21 mm to 2.90 ± 0.20 mm) (P < 0.001). At 36 months, tooth level analysis (Class III and Class IV groups) found less residual REC and increased KT in the test group compared with the control group (P < 0.01). Significantly less pain was reported at 2, 7, and 14 days follow-up post-surgery in the test group (P < 0.001). CONCLUSIONS: The addition of EMD to CTG results in improved root coverage outcomes and higher amounts of KT width 36 months after treatment of Class III-IV REC on mandibular anterior teeth. The adjunctive use of EMD also resulted in significantly reduced pain 14 days post-surgery.

A 3-year prospective clinical and patient-centered trial on subepithelial connective tissue graft with or without enamel matrix derivative in Class I-II Miller recessions.

BACKGROUND AND OBJECTIVE: The study compared clinical and patient-centered outcomes of subepithelial connective tissue graft (CTG) with and without enamel matrix derivative (EMD) in the treatment of Class I-II Miller periodontal recession defects. MATERIAL AND METHODS: This prospective clinical study evaluated 80 patients over a 3 years follow-up in a private periodontal practice. A total of 144 maxillary and mandibular anterior teeth were divided into two groups: group 1 (CTG with EMD-80 teeth) and group 2 (CTG only-64 teeth). Recession (REC), keratinized tissue (KT) width, % root overage, patient-centered outcomes, and pain visual analog scale (P-VAS) were compared between the two groups. RESULTS: At 3 years follow-up at a patient level, statistically significant changes in REC were achieved in both group 1 (4.65 ± 1.84 to 0.39 ± 0.19 mm) and group 2 (4.43 ± 1.11 to 0.92 ± 0.43 mm). Complete root coverage (CRC) was achieved in 66.4% of group 1 and 50.1% of group 2. At both patient and tooth level, the 3-year outcomes were superior for group 1 compared with group 2 in terms of % root coverage, REC, and KT width. Clinical attachment loss (CAL) was reduced in group 1 compared with group 2 at the tooth level analysis only (<.01). Significantly less pain was reported using the pain visual analog Scale (P < .001) at the two weeks follow-up post-surgery in group 1. CONCLUSIONS: Addition of EMD results in improved root coverage outcomes and higher amounts of keratinized tissue width 36 months after treatment of multiple adjacent recessions on maxillary and mandibular anterior teeth. The adjunctive use of EMD also resulted in significantly reduced pain 14 days after the surgery.

Hydrophilic titanium surface-induced macrophage modulation promotes pro-osteogenic signalling.

OBJECTIVES: As biomaterial-induced modulation of mediators of the immune response may be a potential therapeutic approach to enhance wound healing events, the aim of this study was to delineate the effects of titanium surface modification on macrophage phenotype and function. MATERIAL AND METHODS: Rodent bone marrow-derived macrophages were polarized into M1 and M2 phenotypes and cultured on micro-rough (SLA) and hydrophilic modified SLA (modSLA) titanium discs. Macrophage phenotype and cytokine secretion were subsequently assessed by immunostaining and ELISA, respectively. Osteoblast gene expression in response to culture in the M1 and M2 macrophage conditioned media was also evaluated over 7 days by RT-PCR. RESULTS: M1 macrophage culture on the modSLA surface promoted an M2-like phenotype as demonstrated by marked CD163 protein expression, Arg1 gene expression and the secretion of cytokines that significantly upregulated in osteoblasts the expression of genes associated with the TGF-ß/BMP signalling pathway and osteogenesis. In comparison, M2 macrophage culture on SLA surface promoted an inflammatory phenotype and cytokine profile that was not conducive for osteogenic gene expression. CONCLUSIONS: Macrophages are able to alter or switch their phenotype according to the signals received from the biomaterial surface. A hydrophilic micro-rough titanium surface topography elicits a macrophage phenotype associated with reduced inflammation and enhanced pro-osteogenic signalling.

The influence of high-dose systemic zoledronate administration on osseointegration of implants with different surface topography.

AIM: To evaluate the influence of systemic zoledronate administration on the osseointegration of titanium implants with different surface topography in rat maxillae. METHODS: Twenty Sprague-Dawley rats were divided into two groups-test (bisphosphonate) and control (healthy). Bisphosphonate administration began three weeks prior to implant placement, and the animals received zoledronate (66 µg/kg) three times per week. Forty endosseous implants with a moderately rough (20 implants) or a turned surface (20 implants) were immediately placed bilaterally into extraction sockets of maxillary first molars. Animals were sacrificed after 14 and 28 days of healing, and en bloc specimens were harvested for histological and histomorphometric analysis. Osseointegration was quantified by measuring the percentage of bone-to-implant contact. RESULTS: Bone-to-implant contact (BIC) (mean ± SD) values of moderately rough and turned implants at day 14 in test group were 17.62 ± 6.68 and 10.69 ± 1.48, respectively, while in the control group, they were 46.36 ± 5.08 and 33.29 ± 8.89, respectively. At day 28, BIC values of moderately rough and turned implants in the test group were 25.94 ± 7.87 and 7.83 ± 4.30, respectively, while in the control group, they were 72.99 ± 6.60 and 47.62 ± 18.19, respectively. Statistically significant higher BIC values were measured on moderately rough implants compared to turned implants at 28 days, and the control group compared to the test group for both implant surfaces. Histological observations for the control and the test groups demonstrated initial bone formation around moderately rough implants not only on the surface of the parent bone, as was the case with the turned surfaced implants, but also along the implant surface itself. CONCLUSIONS: Systemic zoledronate administration negatively influences osseointegration. Osseointegration was enhanced adjacent to moderately rough compared to turned implants in both the presence and absence of systemic zoledronate administration. Therefore, topographical surface modification may partially offset the negative impact of zoledronate administration.