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Periodontal diseases are initiated by Gram-negative tooth-associated microbial biofilms that elicit a host response, with resultant osseous and soft tissue destruction. In response to endotoxins derived from periodontal pathogens, several osteoclast-related mediators target the destruction of alveolar bone and supporting connective tissues. Major drivers of this aggressive tissue destruction are matrix metalloproteinases (MMPs), cathepsins, and other osteoclast-derived enzymes. This article focuses on the downstream factors of the osteoclast responsible for the degradation of bone and soft tissues around teeth and oral implants. Furthermore, therapeutic approaches that target MMP-2, -8, and -9 inhibition, such as MMP inhibitors, chemically modified tetracyclines, and subantimicrobial formulations of tetracycline analogues, are discussed. The use of rapid, chair-side tests of MMP activity, in particular for MMP-8 and bone collagen fragments, show strong potential as non-invasive measures of tissue health or disease. In addition, studies using other agents for the preservation of bone mass, such as bisphosphonates that inhibit osteoclast recruitment, are highlighted. The application of these bone-preservation strategies to periodontal management and treatment are discussed in the context of high-risk patients susceptible to disease reactivation or disease complications. [ABSTRACT FROM AUTHOR]

Background: The CXC chemokine receptor 4 (CXCR4) and its ligand, stromal cell-derived factor-1 (SDF-1alpha or CXC chemokine ligand 12) are involved in the trafficking of leukocytes into and out of extravascular tissues. The purpose of this study was to determine whether SDF-1alpha secreted by host cells plays a role in recruiting inflammatory cells into the periodontia during local inflammation.Methods: SDF-1alpha levels were determined by enzyme-linked immunosorbent assay in gingival crevicular fluid (GCF) of 24 individuals with periodontitis versus healthy individuals in tissue biopsies and in a preclinical rat model of Porphyromonas gingivalis lipopolysaccharide-induced experimental bone loss. Neutrophil chemotaxis assays were also used to evaluate whether SDF-1alpha plays a role in the recruitment of host cells at periodontal lesions.Results: Subjects with periodontal disease had higher levels of SDF-1alpha in their GCF compared to healthy subjects. Subjects with periodontal disease who underwent mechanical therapy demonstrated decreased levels of SDF-1alpha. Immunohistologic staining showed that SDF-1alpha and CXCR4 levels were elevated in samples obtained from periodontally compromised individuals. Similar results were observed in the rodent model. Neutrophil migration was enhanced in the presence of SDF-1alpha, mimicking immune cell migration in periodontal lesions.Conclusions: SDF-1alpha may be involved in the immune defense pathway activated during periodontal disease. Upon the development of diseased tissues, SDF-1alpha levels increase and may recruit host defensive cells into sites of inflammation. These studies suggest that SDF-1alpha may be a useful biomarker for the identification of periodontal disease progression. [ABSTRACT FROM AUTHOR]

PURPOSE: Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of periodontia. Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a well-known biomarker of bone turnover, and as such is a potential indicator of osseous metabolic activity. The objective of this study was to evaluate the release of the ICTP into the periodontal wound fluid (WF) following periodontal reconstructive surgery using local delivery of highly purified recombinant human PDGF (rhPDGF)-BB. METHODS: Forty-seven human subjects at five treatment centres possessing chronic severe periodontal disease were monitored longitudinally for 24 weeks following PDGF regenerative surgical treatment. Severe periodontal osseous defects were divided into one of three groups and treated at the time of surgery with either: beta-tricalcium phosphate (TCP) osteoconductive scaffold alone (active control), beta-TCP+0.3 mg/ml of rhPDGF-BB, or beta-TCP+1.0 mg/ml of rhPDGF-BB. WF was harvested and analysed for local ICTP levels by radioimmunoassay. Statistical analysis was performed using analysis of variance and an area under the curve analysis (AUC). RESULTS: The 0.3 and 1.0 mg/ml PDGF-BB treatment groups demonstrated increases in the amount of ICTP released locally for up to 6 weeks. There were statistically significant differences at the week 6 time point between beta-TCP carrier alone group versus 0.3 mg/ml PDGF-BB group (p<0.05) and between beta-TCP alone versus the 1.0 mg/ml PDGF-BB-treated lesions (p<0.03). The AUC analysis revealed no statistical differences amongst groups. CONCLUSION: This study corroborates the release of ICTP as a measure of active bone turnover following local delivery of PDGF-BB to periodontal osseous defects. The amount of ICTP released from the WF revealed an early increase for all treatment groups. Data from this study suggests that when PDGF-BB is delivered to promote periodontal tissue engineering of tooth-supporting osseous defects, there is a direct effect on ICTP released from the wound. [ABSTRACT FROM AUTHOR]

Periodontal and peri-implant diseases are primarily biofilm-induced pathologies in susceptible hosts affecting the periodontium and dental implants. Differences in disease susceptibility, severity, and patterns of progression have been attributed to immune regulatory mechanisms such as epigenetics. DNA methylation is an essential epigenetic mechanism governing gene expression that plays pivotal roles in genomic imprinting, chromosomal stability, apoptosis, and aging. Clinical studies have explored DNA methylation inhibitors for cancer treatment and predictive methylation profiles for disease progression. In periodontal health, DNA methylation has emerged as critical, evidenced by clinical studies unraveling its complex interplay with inflammatory genes and its regulatory role in periodontitis contributing to disease severity. Human studies have shown that methylation enzymes associated with gene reactivation (e.g., ten-eleven translocation-2) are elevated in periodontitis compared with gingivitis. Dysregulation of these genes can lead to the production of inflammatory cytokines and an altered initial response to bacteria via the toll-like receptor signaling pathway in periodontal diseases. In addition, in peri-implant diseases, this dysregulation can result in altered DNA methylation levels and enzymatic activity influenced by the properties of the titanium surface. Beyond traditional perspectives, recent evidence highlights the involvement of RNA methylation (e.g., N6-methyladenosine [m6A], N6,2'-0-dimethyladenosine [m6Am]) in periodontitis and peri-implantitis lesions, playing vital roles in the innate immune response, production of inflammatory cytokines, and activation of dendritic cells. Both DNA and RNA methylation can influence the gene expression, virulence, and bacterial behavior of well-known periodontal pathogens such as Porphyromonas gingivalis . Alterations in bacterial methylation patterns result in changes in the metabolism, drug resistance, and gene expression related to survival in the host, thereby promoting tissue degradation and chronic inflammatory responses. In summary, the present state-of-the-art review navigates the evolving landscape of DNA and RNA methylation in periodontal and peri-implant diseases, integrating recent developments and mechanisms to reshape the understanding of epigenetic dynamics in oral health., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To assess tissue perfusion changes and wound healing biomarker levels after root coverage procedures with coronally advanced flap in combination with the cross-linked xenogeneic collagen matrix (CCMX), loaded either with a placebo or recombinant human platelet-derived growth factor-BB (rhPDGF)., Methods: This study was designed as a secondary analysis from a previously published clinical trial, and it assessed the tissue perfusion changes over 6 months around multiple gingival recession defects, treated with either with CCMX alone (control) or with CCMX + rhPDGF (test). High frequency Doppler ultrasonography (HFUS) scans were obtained at sites of interest at baseline, 2 weeks, 3 months, and 6 months after surgery. Dynamic tissue perfusion measurements (DTPMs) were performed at the midfacial, interproximal, and transverse aspects of the teeth by an operator, blinded to treatment allocation, using a software package. The expression of different wound healing biomarkers from the gingival crevicular fluid was also assessed., Results: The regression analyses showed similar tissue perfusion changes between the two groups throughout the majority of the 6 months. DTPMs at 2 weeks showed the test group to have significantly higher perfusion relief intensity (pRI, p < 0.001), mean perfused area (pA, p < 0.001), mean blood flow intensity (FI mean , p = 0.021), and total blood flow intensity (FI tot , p = 0.021) at the graft region of interest (ROI) compared to control sites. The test sites also exhibited significantly greater pA (p = 0.033) and blood flow intensity "blue" (FI blue , meaning flow away from the transducer, p = 0.035) at the level of the flap compared to the control sites. At 2 weeks, FI blue of the graft was directly correlated with the final mean root coverage (p = 0.008) and complete root coverage (p = 0.003). FI mean and FI tot of the graft exhibited a direct correlation with volume gain at 6 months (p = 0.031 for both parameters). The final GT gain was correlated to the early DTPMs (pA and FI blue ) of the graft and the flap. The two groups exhibited different expressions of IL-1β, PDFG-BB, and VEGF over 3 months, with the 1-week levels of PDGF-BB that were associated with time to recovery., Conclusions: HFUS allowed exquisite assessment of tissue perfusion occurring at the entire surgical reconstructive regions and also within the flap and the graft. Sites treated with CCMX + rhPDGF exhibited higher DTPMs, primarily within the graft and flap ROIs at the 2-week timepoint compared to sites augmented with CCMX + saline. Early DTPMs at the graft and flap ROIs showed associations with PROMs and the final clinical outcomes., Trial Registration: ClinicalTrials.gov: NCT04462237., (© 2025 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objective: Abaloparatide (ABL) is a synthetic parathyroid hormone-related protein analog developed as an anabolic drug to treat osteoporosis. ABL increases bone mineral density (BMD) of the long bones and spine; however, the influence of ABL on alveolar bone regeneration remains unknown. This study assessed the effects of systemic ABL administration on tooth extraction socket healing and dental implant osseointegration in a preclinical rodent model., Methods: Sprague-Dawley rats received daily subcutaneous injection of ABL (25 μg/kg) or vehicle (VEH) at the time of maxillary first molar (M1) extraction surgery; animals underwent either: (1) unilateral M1 extraction followed by sacrifice at 10 or 42d or (2) bilateral M1 extraction followed by staged implant placement in osteotomies with standardized defects and sacrifice at 21 or 28d., Results: Micro-computed tomography (micro-CT) analysis demonstrated that ABL increased bone volume fraction (p = 0.004) and bone mineral density (BMD) (p = 0.006) of regenerated extraction sockets at 42d. Micro-CT of the femur validated systemic effects of ABL, showing greater trabecular BMD after 6 (p < 0.01), 9 (p < 0.001), and 14 (p < 0.001) weeks of treatment. Histomorphometry confirmed a higher mineralized bone area with ABL treatment in extraction sockets at 42d (p = 0.03) and in the regenerated peri-implant bone at 21d post-implant placement (p = 0.01) compared to control., Conclusion: Systemic ABL administration enhances osteogenesis in extraction sockets prior to implant placement and accelerates peri-implant bone formation in the early phase of healing in the present rodent model., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To identify gingival crevicular fluid (GCF)-derived inflammatory markers of periodontitis progression and periodontal treatment impact., Methods: Periodontally healthy (H; n = 112) and periodontitis (P; n = 302) patients were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Levels of 64 biomarkers were measured in the GCF samples collected at each visit from progressing (n = 12 sites in H; n = 76 in P) and stable (n = 100 in H, n = 225 in P) sites. Clinical parameters and log-transformed analyte levels were averaged within clinical groups at each time point and analysed using linear mixed models., Results: During monitoring, progressing sites had significantly higher levels of IL-1β, MMP-8, IL-12p40, EGF and VEGF. MMP-9 and Periostin were significantly more elevated in stable sites. Distinct cytokine profiles were observed based on baseline PD. Treatment led to significant reductions in Eotaxin, Flt-3L, GDF-15, GM-CSF, IL-1β, IL-17, MIP-1d, RANTES and sCD40L, and increases in IP-10 and MMP-9., Conclusion: Distinct cytokine signatures observed in stable and progressing sites were maintained over time in the absence of treatment and significantly affected by NSPT., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Aim: To assess the Doppler ultrasonographic tissue perfusion at dental implant sites augmented with connective tissue graft (CTG) using coronally advanced flap (CAF) or tunnel technique (TUN)., Materials and Methods: Twenty-eight patients presenting with isolated healthy peri-implant soft-tissue dehiscence (PSTD) were included in this randomized clinical trial. PSTDs were treated with either CAF + CTG or TUN + CTG. Ultrasound scans were taken at baseline, 1 week, 1 month, 6 months and 12 months. Tissue perfusion at the mid-facial, mesial and distal aspects of the implant sites was assessed by colour Doppler velocity (CDV) and power Doppler imaging (PDI). Early vascularization of the graft and the flap at 1 week and at 1 month were evaluated via dynamic tissue perfusion measurements (DTPMs), including flow intensity (FI), mean perfusion relief intensity (pRI) and mean perfused area (pA)., Results: Regression analysis did not reveal significant differences in terms of mid-facial CDV and PDI changes between CAF and TUN over 12 months (p > .05), while significant differences between the two groups were observed at the interproximal areas (p < .001 for both CDV and PDI changes). Higher early DTPMs were observed at the TUN-treated sites in terms of mean FI of the graft (p = .027) and mean FI (p = .024) and pRI of the flap (p = .031) compared with CAF-treated sites at 1 week. Assessment of the FI direction showed that CTG perfusion at 1 week and at 1 month mainly occurred from the flap towards the implant/bone. Early tissue perfusion outcomes were found to be associated with the 12-month mean PSTD coverage and mucosal thickness gain., Conclusions: Doppler ultrasonography shows tissue perfusion changes occurring at implant sites augmented with CTG. The main differences in tissue perfusion between CAF and TUN were observed at the interproximal sites, with early perfusion associated with clinical and volumetric outcomes at 12 months., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Aim: To identify serum- and salivary-derived inflammatory biomarkers of periodontitis progression and determine their response to non-surgical treatment., Materials and Methods: Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Participants were classified according to disease progression: P0 (no sites progressed; P1: 1-2 sites progressed; P2: 3 or more sites progressed). Ten salivary and five serum biomarkers were measured using Luminex. Log-transformed levels were compared over time according to baseline diagnosis, progression trajectory and after NSPT. Significant differences were sought using linear mixed models., Results: P2 presented higher levels (p < .05) of salivary IFNγ, IL-6, VEGF, IL-1β, MMP-8, IL-10 and OPG over time. Serum analytes were not associated with progression. NSPT led to clinical improvement and significant reduction of IFNγ, IL-6, IL-8, IL-1β, MMP-8, IL-10, OPG and MMP-9 in saliva and of CRP, MMP-8, MMP-9 and MPO in serum., Conclusions: Periodontitis progression results from a sustained pro-inflammatory milieu that is reflected in salivary biomarkers, but less so in serum, likely because of the limited amount of progression per patient. NSPT can significantly decrease the levels of several salivary analytes., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: Bone anabolic drugs used for the pharmacologic treatment of osteoporosis have the potential to enhance alveolar bone regeneration to improve implant success. There are no US Food and Drug Administration-approved drugs indicated to improve oral bone density around teeth or implants., Methods: The authors summarized expert opinions on a novel coordinated treatment approach leveraging the effects of systemic bone anabolic drugs to enhance dental implant therapy in patients with osteoporosis and a dual referral model for physicians and dentists to address the clinical needs of patients with osteoporosis from a comprehensive perspective of oral-systemic health. Interviews of key opinion leaders were conducted with a bone health specialist group consisting of specialists in orthopedic surgery, internal medicine, geriatrics, endocrinology, and clinical densitometry and a surgical dental specialist group consisting of periodontists and oral surgeons., Results: Overall, both groups shared positive feedback on the idea of strategically timing administration of anabolic osteoporosis drugs with dental treatment. Both groups expressed interest in the dual referral model., Conclusions: The feedback of key opinion leaders supported the coordinated bone anabolic therapy concept and identified a need for improved interdisciplinary collaboration, education, and communication to realize the synergies of physician-dentist clinical cooperation., Practical Implications: Strategic timing of osteoporosis therapy could improve skeletal bone health and reduce fracture risk while offering adjunctive dental benefits., Competing Interests: Disclosure Dr. Berkey is the president of The Avenues Company. None of the other authors reported any disclosures., (Copyright © 2024 American Dental Association. Published by Elsevier Inc. All rights reserved.)

At present, a lack of consensus exists regarding the clinical impact of osteoporosis on alveolar bone metabolism during implant osseointegration. While limited preclinical and clinical evidence demonstrates a negative influence of osteoporosis on dental extraction socket healing, no preclinical studies offer data on the results of implant placement in 6-mo-old, ovariectomized (OVX) Sprague-Dawley rats. This study aimed to investigate the outcomes of dental tooth extraction socket healing and implant placement in a rodent model of osteoporosis following daily vehicle (VEH) or abaloparatide (ABL) administration. Micro-CT and histologic analysis demonstrated signs of delayed wound healing, consistent with alveolar osteitis in extraction sockets following 42 d of healing in both the VEH and ABL groups. In a semiquantitative histological analysis, the OVX-ABL group demonstrated a tendency for improved socket regeneration with a 3-fold greater rate for moderate socket healing when compared to the OVX-VEH group (43% vs 14%), however, this finding was not statistically significant ( p =.11). No significant differences were observed between vehicle and test groups in terms of implant outcomes (BMD and bone volume/total volume) at 14- and 21-d post-implant placement. Abaloparatide (ABL) significantly increased BMD of the femoral shaft and intact maxillary alveolar bone sites in OVX animals, demonstrating the therapeutic potential for oral hard tissue regeneration. The present model involving estrogen-deficiency-induced bone loss demonstrated an impaired healing response to dental extraction and implant installation., Competing Interests: B.M. and B.L. are employees of Radius Health, Inc. P.K. is a consultant to Amgen Inc, AgNovos, Ascendis, Ashi Bio, Mesentech, NextCure, Beren Therapeutics, Radius Health, UCB, and Myovant/Sumimoto., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Aim: The aim of this study is to assess early wound healing expression of local angiogenic biomarkers following connective tissue graft (CTG) at dental implant sites., Methods: Twenty-eight subjects with single dental implants exhibiting a soft tissue dehiscence were included and randomly treated with CTG, either with coronally advanced flap (CAF) or with tunnel technique (TUN). Peri-implant crevicular fluid (PICF) was collected at the midfacial and midlingual aspect of the implant sites at baseline and at 3, 7, 14, 30, and 90 days after the surgical intervention. The expression of angiogenin (ANG), fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinases-2 (TIMP-2), and vascular endothelial growth factor (VEGF) was investigated over a period of 3 months. Patient-reported outcomes, clinical measurements, and ultrasonography scans at multiple time points were also evaluated., Results: The longitudinal regression revealed a significant difference in the expression of VEGF and TIMP-2 between CAF- and TUN-treated sites over 3 months (p = .033 and p = .004, respectively), whereas no significant differences were observed for ANG, FGF-2 and PDGF between the two groups. At 7 days, a direct correlation was observed between ANG levels and ultrasonographic color velocity in the CAF group (p < .001) and between ANG levels and ultrasonographic color power in the TUN group (p = .028). VEGF levels and ultrasonographic mean perfused area of the CTG were significantly correlated at the 7-day time point (p < .001 for both CAF and TUN). The expression of VEGF at 7 days was directly associated with mucosal thickness gain at 1 year (p < .001 for both groups). Early TIMP-2 expression showed an inverse correlation with time to recovery (p = .002). TIMP-2 levels at 3 months exhibited inverse correlations with mean dehiscence coverage (p = .004) and the rate of complete dehiscence coverage (p = .012)., Conclusion: PICF biomarkers can be used to monitor early wound healing events following soft tissue grafting at implant sites. VEGF and TIMP-2 showed correlations with the 1-year clinical and volumetric outcomes, as well as with post-operative patient-reported outcomes and Doppler Ultrasonographic tissue perfusion-related parameters., (© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Artificial intelligence (AI) is increasingly applied across all disciplines of medicine, including dentistry. Oral health research is experiencing a rapidly increasing use of machine learning (ML), the branch of AI that identifies inherent patterns in data similarly to how humans learn. In contemporary clinical dentistry, ML supports computer-aided diagnostics, risk stratification, individual risk prediction, and decision support to ultimately improve clinical oral health care efficiency, outcomes, and reduce disparities. Further, ML is progressively used in dental and oral health research, from basic and translational science to clinical investigations. With an ML perspective, this review provides a comprehensive overview of how dental medicine leverages AI for diagnostic, prognostic, and generative tasks. The spectrum of available data modalities in dentistry and their compatibility with various methods of applied AI are presented. Finally, current challenges and limitations as well as future possibilities and considerations for AI application in dental medicine are summarized., Competing Interests: BF reports prior speaking fees from dentalXr.ai and synMedico. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feher, Tussie and Giannobile.)

Introduction: The aim of our study was to investigate the impact of diabetes-related factors on the dental disease outcomes of diabetes patients in Trincomalee, Sri Lanka. Materials and Methods: Dental data were collected from 80 type-2-diabetic individuals. A dental risk score was calculated based on the frequency of dental outcomes observed and categorized as low risk (≤3 dental outcomes) and high risk (>3 dental outcomes). Results: In this cohort of men and women with type 2 diabetes, there was a high frequency of periodontal related outcomes, including missing teeth (70%), gingival recessions (40%), tooth mobility (41%), and bleeding (20%). Thirty-nine (39%) of participants had high dental risk, while forty-nine (61%) had low risk. Conclusions : After controlling for age, participants with higher capillary blood glucose levels had 3-fold greater odds of a high dental risk score (OR = 2.93, 95%CI = 1.13, 7.61). We found that poor glycemic control indicated by elevated capillary blood glucose was associated with increased dental risk.

Aim: To determine the effects of RVX-208, a selective bromodomain and extra-terminal domain (BET) inhibitor targeting bromodomain 2 (BD2), on periodontal inflammation and bone loss., Materials and Methods: Macrophage-like cells (RAW264.7) and human gingival epithelial cells were challenged by Porphyromonas gingivalis (Pg) with or without RVX-208. Inflammatory gene expression and cytokine production were measured by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RAW264.7 cells were induced to osteoclast differentiation. After RVX-208 treatment, osteoclast differentiation was evaluated by histology, tartrate-resistant-acid-phosphatase (TRAP) activity and the expression of osteoclast-specific genes. The effect of RVX-208 on osteoclast transcriptome was studied by RNA sequencing. Periodontitis was induced in rats by ligature and local RVX-208 treatment was administered every other day. Alveolar bone loss was measured by micro-computed tomography., Results: RVX-208 inhibited inflammatory gene expression and cytokine production in Pg-infected cells. Osteoclast differentiation was inhibited by RVX-208, as evidenced by reduced osteoclast number, TRAP activity and osteoclast-specific gene expression. RVX-208 displayed a more selective and less profound suppressive impact on transcriptome compared with pan-BET inhibitor, JQ1. RVX-208 administration prevented the alveolar bone loss in vivo., Conclusions: RVX-208 regulated both upstream (inflammatory cytokine production) and downstream (osteoclast differentiation) events that lead to periodontal tissue destruction, suggesting that it may be a promising 'epi-drug' for the prevention of periodontitis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A 13-year follow-up was conducted of a short-term investigation of the use of living cellular construct (LCC) versus free gingival graft (FGG) for keratinized tissue width (KTW) augmentation in natural dentition, to evaluate the long-term outcomes and assess the changes occurring since the end of the original 6-month study., Methods: Twenty-four subjects out of the original 29 enrolled participants were available at the 13-year follow-up. The primary endpoint was the number of sites demonstrating stable clinical outcomes from 6 months to 13 years (defined as KTW gain, stability, or ≤0.5 mm of KTW loss, together with reduction, stability, or increase of probing depth, and recession depth [REC] ≤0.5 mm). Secondary outcomes included the assessment of KTW, attached gingiva width (AGW), REC, clinical attachment level, esthetics, and patient-reported outcomes at the 13-year visit, assessing the changes from baseline to 6 months., Results: Nine sites per group (42.9%) were found to have maintained stable (≤0.5 mm or improved) clinical outcomes from 6 months to 13 years. No significant differences were observed for the clinical parameters between LCC and FGG from 6 months to 13 years. However, the longitudinal mixed model analysis showed that FGG delivered significantly better clinical outcomes over 13 years (p < 0.01). LCC-treated sites exhibited superior esthetic outcomes compared to FGG-treated sites at 6 months and 13 years (p < 0.01). Patient-evaluated esthetics were significantly higher for LCC over FGG (p < 0.01). Patient overall treatment preference was also in favor of LCC (p < 0.01)., Conclusions: A similar stability of the treatment outcomes from 6 months to 13 years was found for LCC- and FGG-treated sites, with both approaches shown to be effective in augmenting KTW and AGW. However, superior clinical outcomes were found for FGG over 13 years, while LCC was associated with better esthetics and patient-reported outcomes than FGG., (© 2023 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Aim: To evaluate the efficacy of coronally advanced flap (CAF) versus tunnel technique (TUN) in covering isolated mid-facial peri-implant soft tissue dehiscences (PSTDs)., Materials and Methods: Twenty-eight participants presenting with isolated non-molar implants exhibiting PSTDs were enrolled and randomized to receive either CAF or TUN, both with a connective tissue graft (CTG). The primary outcome of the study was the percentage of mean PSTD coverage at 12 months. Secondary endpoints included the frequency of complete PSTD coverage, changes in keratinized mucosa width (KMW) and horizontal mucosal thickness (MT), as assessed with transgingival probing, 3D optical scanning and ultrasonography, professional aesthetic evaluation and patient-reported outcome measures (PROMs)., Results: At 12 months, the mean PSTD coverage of the CAF and TUN groups was 90.23% and 59.76%, respectively (p = .03). CAF-treated sites showed a substantially higher frequency of complete PSTD coverage (p = .07), together with significantly greater gain of KMW (p = .01), increase in MT (p = .02), volumetric gain (p < .01) and professional aesthetic outcomes (p = .01). Both interventions showed an improvement in patient-reported aesthetics and a reduction of the anxiety related to the appearance of the implant compared to baseline, with the CAF group obtaining significantly higher scores (p = .03 for both PROMs)., Conclusions: CAF + CTG resulted in superior PSTD coverage outcomes, greater gain in KMW and MT, and better PROMs than TUN + CTG for the treatment of isolated PSTDs (ClinicalTrials.gov NCT03498911)., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Palatal-tissue harvesting is a routinely performed procedure in periodontal and peri-implant plastic surgery. Over the years, several surgical approaches have been attempted with the aim of obtaining autogenous soft-tissue grafts while minimizing patient morbidity, which is considered the most common drawback of palatal harvesting. At the same time, treatment errors during the procedure may increase not only postoperative discomfort or pain but also the risk of developing other complications, such as injury to the greater palatine artery, prolonged bleeding, wound/flap sloughing, necrosis, infection, and inadequate graft size or quality. This chapter described treatment errors and complications of palatal harvesting techniques, together with approaches for reducing patient morbidity and accelerating donor site wound healing. The role of biologic agents, photobiomodulation therapy, local and systemic factors, and genes implicated in palatal wound healing are also discussed., (© 2022 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

Objectives: This randomized clinical trial assessed changes in protein biomarker levels and bacterial profiles after surgical reconstructive therapy of peri-implantitis and investigated whether the adjunctive use of Er:YAG laser impacts protein biomarker and microbial outcomes., Materials and Methods: Twenty-four patients received surgical reconstructive therapy for peri-implantitis with guided bone regeneration following mechanical debridement with (test) or without (control) the adjunctive irradiation of Er:YAG laser. Bacterial and peri-implant crevicular fluid (PICF) samples were collected over 6 months and analyzed with bacterial qPCR and luminex multiplex assays., Results: Surgical reconstructive treatment significantly affected the concentration of PICF protein biomarkers, including a 50% reduction in IL-1β between 2 and 4 weeks (p < .0001). Both MMP-9 (p < .001) and VEGF (p < .05) levels steadily decreased after treatment. In the laser group, the peak increase in IL-1β was attenuated at 2 weeks, followed by significant reduction in MMP-9 (p < .01) and VEGF (p < .05) across all follow-up appointments compared with the control nonlaser group. The total bacterial load was reduced 2 weeks after treatment, especially in the laser group, but recolonized to presurgical levels after 4 weeks in both groups (p < .01). The composition of selective pathogens varied significantly over the follow-up, but recolonization patterns did not differ between groups., Conclusions: Reconstructive therapy of peri-implantitis significantly altered PICF protein biomarker and microbial levels during the healing process. The adjunctive use of Er:YAG laser significantly modulated the inflammatory response through reduced levels of MMP-9 and VEGF during the postsurgical period. The bacterial load was reduced immediately after therapy, but recolonization was observed by 4 weeks in both groups., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Scientific advancements in biomaterials, cellular therapies, and growth factors have brought new therapeutic options for periodontal and peri-implant reconstructive procedures. These tissue engineering strategies involve the enrichment of scaffolds with living cells or signaling molecules and aim at mimicking the cascades of wound healing events and the clinical outcomes of conventional autogenous grafts, without the need for donor tissue. Several tissue engineering strategies have been explored over the years for a variety of clinical scenarios, including periodontal regeneration, treatment of gingival recessions/mucogingival conditions, alveolar ridge preservation, bone augmentation procedures, sinus floor elevation, and peri-implant bone regeneration therapies. The goal of this article was to review the tissue engineering strategies that have been performed for periodontal and peri-implant reconstruction and implant site development, and to evaluate their safety, invasiveness, efficacy, and patient-reported outcomes. A detailed systematic search was conducted to identify eligible randomized controlled trials reporting the outcomes of tissue engineering strategies utilized for the aforementioned indications. A total of 128 trials were ultimately included in this review for a detailed qualitative analysis. Commonly performed tissue engineering strategies involved scaffolds enriched with mesenchymal or somatic cells (cell-based tissue engineering strategies), or more often scaffolds loaded with signaling molecules/growth factors (signaling molecule-based tissue engineering strategies). These approaches were found to be safe when utilized for periodontal and peri-implant reconstruction therapies and implant site development. Tissue engineering strategies demonstrated either similar or superior clinical outcomes than conventional approaches for the treatment of infrabony and furcation defects, alveolar ridge preservation, and sinus floor augmentation. Tissue engineering strategies can promote higher root coverage, keratinized tissue width, and gingival thickness gain than scaffolds alone can, and they can often obtain similar mean root coverage compared with autogenous grafts. There is some evidence suggesting that tissue engineering strategies can have a positive effect on patient morbidity, their preference, esthetics, and quality of life when utilized for the treatment of mucogingival deformities. Similarly, tissue engineering strategies can reduce the invasiveness and complications of autogenous graft-based staged bone augmentation. More studies incorporating patient-reported outcomes are needed to understand the cost-benefits of tissue engineering strategies compared with traditional treatments., (© 2022 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd.)

A biologic is a therapeutic agent with biological activity that is administered to achieve an enhanced regenerative or reparative effect. The use of biologics has progressively become a core component of contemporary periodontal practice. However, some questions remain about their safety, indications, and effectiveness in specific clinical scenarios. Given their availability for routine clinical use and the existing amount of related evidence, the goal of this American Academy of Periodontology (AAP) best evidence consensus (BEC) was to provide a state-of-the-art, evidence-based perspective on the therapeutic application of autologous blood-derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet-derived growth factor BB (rhPDGF-BB), and recombinant human bone morphogenetic protein 2 (rhBMP-2). A panel of experts with extensive knowledge on the science and clinical application of biologics was convened. Three systematic reviews covering the areas of periodontal plastic surgery, treatment of infrabony defects, and alveolar ridge preservation/reconstruction and implant site development were conducted a priori and provided the foundation for the deliberations. The expert panel debated the merits of published data and exchanged experiential information to formulate evidence-based consensus statements and recommendations for clinical practice and future research. Based on an analysis of the current evidence and expert opinion, the panel concluded that the appropriate use of biologics in periodontal practice is generally safe and provides added benefits to conventional treatment approaches. However, therapeutic benefits and risks range based on the specific biologics used as well as patient-related local and systemic factors. Given the limited evidence available for some indications (e.g., gingival augmentation therapy, alveolar ridge preservation/reconstruction, and implant site development), future clinical studies that can expand the knowledge base on the clinical use of biologics in periodontal practice are warranted., (© 2022 The Authors. Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Importance: Although many academic institutions have implemented infection control and prevention protocols, including regular asymptomatic self-testing, in response to the COVID-19 pandemic, the outcomes of mandatory surveillance testing programs at academic dental institutions that offer direct patient-facing clinical care has not yet been reported., Objective: To report the findings of a comprehensive surveillance COVID-19 testing program at an academic dental institution by assessing SARS-CoV-2 positivity rates and the potential association of test positivity with individual-level characteristics such as age, sex, and role., Design, Setting, and Participants: A retrospective cohort study was conducted using SARS-CoV-2 self-testing data from a mandatory surveillance program at the Harvard School of Dental Medicine. Test results obtained between August 24, 2020, and February 28, 2022, from students, faculty, and staff members were analyzed. Testing cadence varied from 1 to 3 times per week depending on risk status. The association of individual characteristics with test positivity was evaluated with univariate analyses and a bayesian multilevel logistic regression model., Exposures: Age by decade, sex, and role or position category (staff members, faculty, and students stratified by their involvement in clinical care activities), testing cadence, and testing date., Main Outcomes and Measures: Positive results from SARS-CoV-2 real-time reverse transcription-polymerase chain reaction self-tests were assessed., Results: Of the 390 study participants, 210 (53.8%) were women. Participants were grouped by age as follows: 20 to 29 years (190 [48.7%]), 30 to 39 years (88 [22.6%]), 40 to 49 years (44 [11.3%]), 50 to 59 years (42 [10.8%]), and 60 years or older (26 [6.7%]). Test results demonstrated an overall 0.27% positivity rate (61 test-positive cases), with a peak weekly positivity rate of 5.12% in the first week of January 2022. The mean (SD) test positivity rate among those involved in clinical activities was 0.25% (0.04) compared with 0.36% (0.09) among nonclinical participants. When adjusting for all considered covariates, test positivity was significantly associated with testing frequency (3 times vs 1 time per week: odds ratio [OR], 1.51 [95% credible interval (CrI), 1.07-3.69]) and timing of the test (after vs during the Alpha wave: OR, 0.33 [95% CrI, 0.11-0.88]; and Omicron vs Alpha: OR, 11.59 [95% CrI, 6.49-22.21]) but not with individual characteristics (age, sex, and role)., Conclusions and Relevance: These findings suggest that implementing an adaptive testing cadence based on the risk status of individuals may be effective in reducing the risk of SARS-CoV-2 infection within an institution. In this study, involvement in clinical activities did not pose additional risk of SARS-CoV-2 infection compared with other in-person activities in the presence of these control measures.

Background: With technological advancements in reconstructive periodontology, traditional protocols for the treatment of gingival recessions (GRs) can be challenged. This manuscript presents preliminary findings of a novel minimally-invasive approach for the regenerative treatment of multiple adjacent GR defects., Methods: Two healthy adults were treated as part of this study. Multiple adjacent GRs in both subjects (1 in the mandible, and 1 in the maxilla) were treated employing a tunneled coronally advanced flap (TCAF) design, with the application of a cross-linked collagen matrix (CCM) that was enriched with recombinant human platelet-derived growth factor-BB (PDGF-BB) that was also applied on the prepared root surfaces. Clinical, ultrasonographic, esthetic, and patient-reported outcomes were observed at approximately 6- and 18-month time points., Results: All sites healed uneventfully after the treatments. Complete root coverage was achieved and maintained throughout the follow-up observations, from 6 to 18 months. Patients reported minimal discomfort and reduction of dentinal hypersensitivity at the augmented sites. The areas augmented with CCM + PDGF-BB revealed an increased soft tissue thickness relative to baseline (pretreatment) measures, as well as reduction in the level of the facial bone dehiscences., Conclusion: This article describes the success of two cases of a novel minimally invasive regenerative approach for the treatment of multiple adjacent GR defects by the TCAF, using a CCM loaded with PDGF-BB. This approach offers potential as a minimally-invasive method to repair multiple adjacent GRs., (© 2022 The Authors. Clinical Advances in Periodontics published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.)

Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue-to-bone interfaces. Inspired by the hierarchical structure of native periodontal tissues, tissue engineering technology provides unique opportunities to coordinate multiple cell types into scaffolds that mimic the natural periodontal structure in vitro. In this study, we designed and fabricated highly ordered multicompartmental scaffolds by melt electrowriting, an advanced 3-dimensional (3D) printing technique. This strategy attempted to mimic the characteristic periodontal microenvironment through multicompartmental constructs comprising 3 tissue-specific regions: 1) a bone compartment with dense mesh structure, 2) a ligament compartment mimicking the highly aligned periodontal ligaments (PDLs), and 3) a transition region that bridges the bone and ligament, a critical feature that differentiates this system from mono- or bicompartmental alternatives. The multicompartmental constructs successfully achieved coordinated proliferation and differentiation of multiple cell types in vitro within short time, including both ligamentous- and bone-derived cells. Long-term 3D coculture of primary human osteoblasts and PDL fibroblasts led to a mineral gradient from calcified to uncalcified regions with PDL-like insertions within the transition region, an effect that is challenging to achieve with mono- or bicompartmental platforms. This process effectively recapitulates the key feature of interfacial tissues in periodontium. Collectively, this tissue-engineered approach offers a fundament for engineering periodontal tissue constructs with characteristic 3D microenvironments similar to native tissues. This multicompartmental 3D printing approach is also highly compatible with the design of next-generation scaffolds, with both highly adjustable compartmentalization properties and patient-specific shapes, for multitissue engineering in complex periodontal defects.

Aim: To evaluate the efficacy of recombinant human platelet-derived growth factor (rhPDGF)-BB combined with a cross-linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF)., Materials and Methods: Thirty patients were enrolled in this triple-blind, randomized, placebo-controlled trial and treated with either CAF + CCM + rhPDGF, or CAF + CCM + saline. The primary outcome was mean root coverage (mRC) at 6 months. Complete root coverage, gain in gingival thickness (GT), keratinized tissue width, volumetric and ultrasonographic changes, and patient-reported outcome measures were also assessed. Mixed-modelling regression analyses were used for statistical comparisons., Results: At 6 months, the mRC of the CCM + rhPDGF and CCM alone groups were 88.25% and 77.72%, respectively (p = .02). A significant gain in GT was consistently observed for both treatment arms, and more so for the patients receiving the matrix containing rhPDGF through time (0.51 vs. 0.80 mm, on average, p = .01). The rhPDGF + CCM treated patients presented greater volume gain, higher soft tissue thickness, and a superior aesthetic score., Conclusion: rhPDGF enhances the clinical, volumetric, and aesthetic outcomes of MAGRs above the results achieved with CAF + CCM alone (ClinicalTrials.gov NCT04462237)., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Periodontitis is a disease characterized by tooth-associated microbial biofilms that drive chronic inflammation and destruction of periodontal-supporting tissues. In some individuals, disease progression can lead to tooth loss. A similar condition can occur around dental implants in the form of peri-implantitis. The immune response to bacterial challenges is not only influenced by genetic factors, but also by environmental factors. Epigenetics involves the study of gene function independent of changes to the DNA sequence and its associated proteins, and represents a critical link between genetic and environmental factors. Epigenetic modifications have been shown to contribute to the progression of several diseases, including chronic inflammatory diseases like periodontitis and peri-implantitis. This review aims to present the latest findings on epigenetic influences on periodontitis and to discuss potential mechanisms that may influence peri-implantitis, given the paucity of information currently available., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

For individuals who have experienced tooth loss, dental implants are an important treatment option for oral reconstruction. For these patients, alveolar bone augmentation and acceleration of osseointegration optimize implant stability. Traditional oral surgery often requires invasive procedures, which can result in prolonged treatment time and associated morbidity. It has been previously shown that chemical vapor deposition (CVD) polymerization of functionalized [2.2]paracyclophanes can be used to anchor gene encoding vectors onto biomaterial surfaces and local delivery of a bone morphogenetic protein (BMP)-encoding vector can increase alveolar bone volume and density in vivo. This study is the first to combine the use of CVD technology and BMP gene delivery on titanium for the promotion of bone regeneration and bone to implant contact in vivo. BMP-7 tethered to titanium surface enhances osteoblast cell differentiation and alkaline phosphatase activity in vitro and increases alveolar bone regeneration and % bone to implant contact similar to using high doses of exogenously applied BMP-7 in vivo. The use of this innovative gene delivery strategy on implant surfaces offers an alternative treatment option for targeted alveolar bone reconstruction., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Human bone marrow stromal cell (hBMSC)-derived exosomes are promising therapeutics for inflammatory diseases due to their unique microRNA (miRNA) and protein cargos. Periodontal diseases often present with chronicity and corresponding exuberant inflammation, which leads to loss of tooth support. In this study, we explored whether hBMSC exosomes can affect periodontitis progression. hBMSC exosomes were isolated from cell culture medium through sequential ultracentrifugation. miRNAs and proteins that were enriched in hBMSC exosomes were characterized by RNA sequencing and protein array, respectively. hBMSC exosomes significantly suppressed periodontal keystone pathogen Porphyromonas gingivalis- triggered inflammatory response in macrophages in vitro. Transcriptomic analysis suggested that exosomes exerted their effects through regulating cell metabolism, differentiation, and inflammation resolution. In vivo, weekly exosome injection into the gingival tissues reduced the tissue destruction and immune cell infiltration in rat ligature-induced periodontitis model. Collectively, these findings suggest that hBMSC-derived exosomes can potentially be used as a host modulation agent in the management of periodontitis.

The objective of this pilot clinical study was to identify salivary biomarkers that are associated with periodontal disease and measures of diabetic autonomic dysfunction. Saliva samples from 32 participants were obtained from 3 groups: healthy (H), type 1 diabetes mellitus (DM), and type 1 diabetes mellitus with neuropathy (DMN). Based on the periodontal examination, individuals' mean Periodontal Screening and Recording scores were categorized into two groups (periodontally healthy and gingivitis), and correlated to specific salivary inflammatory biomarkers assessed by a customized protein array and enzyme assay. The mean salivary IgA level in DM was 9211.5 ± 4776.4 pg/ml, which was significantly lower than H (17,182.2 ± 8899.3 pg/ml). IgA in DMN with healthy periodontium was significantly lower (5905.5 ± 3124.8 pg/ml) compared to H, although IgA levels in DMN patients with gingivitis (16,894. 6 ± 7084.3) were not. According to the result of a logistic regression model, IgA and periodontal condition were the indicators of the binary response given by H versus DM, and H versus DMN, respectively. These data suggest that selected salivary biomarkers, such as IgA, combined with a periodontal examination prior to obtaining salivary samples can offer a non-invasive method to assess risk for developing diabetic neuropathy., (© 2022. The Author(s).)

Aim: To assess the prognostic value of soft tissue phenotype modification following root coverage procedures for predicting the long-term (10-year) behaviour of the gingival margin., Materials and Methods: Participants from six randomized clinical trials on root coverage procedures at the University of Michigan were re-invited for a longitudinal evaluation. Clinical measurements were obtained by two calibrated examiners. A data-driven approach to model selection with Akaike information criterion (AIC) was carried out via multilevel regression analyses and partial regression plotting for changes in the level of the gingival margin over time and interactions with the early (6-month) results of soft tissue phenotypic modification., Results: One-hundred and fifty-seven treated sites in 83 patients were re-assessed at the long-term recall. AIC-driven model selection and regression analyses demonstrated that 6-month keratinized tissue width (KTW) and gingival thickness (GT) influenced the trajectory of the gingival margin similarly in a concave manner; however, GT was the driving determinant that predicted significantly less relapse in the treatments, with stability of the treated gingival margin obtained beyond values of 1.46 mm., Conclusions: Among a compliant patient cohort, irrespective of the rendered therapy, the presence of at least 1.5 mm KTW and 1.46 mm GT was correlated with the long-term stability of the gingival margin., (© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Background: To investigate the pro-inflammatory cytokine profiles in patients with or without cardiovascular disease (CVD) and with or without peri-implantitis., Methods: Serum, peri-implant crevicular fluid (PICF), and gingival crevicular fluid (GCF) were collected from patients with (n = 82) or without CVD (n = 46) at the most severe peri-implantitis site including sites with periodontitis. A panel of proinflammatory molecules including high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-1 beta (IL-1β), IL-6, plasma tumor necrosis factor-alpha (TNF-α), matrix metallo-proteinase-8 (MMP-8), osteoprotegerin (OPG), vascular endothelial growth factor (VEGF), IL-17, IL-8, tissue inhibitor of metalloproteinase-2 (TIMP-2), myeloperoxidase (MPO), and prostaglandin E 2 (PGE 2 ) were analyzed using human custom Quantibody arrays. Krunskal-Wallis test was used to compare groups. The diagnostic ability of each biomarker was assessed using chi-square test and ROC analysis., Results: Serum IL-1β, TNF-α and fibrinogen were significantly higher in CVD patients than those without. Serum fibrinogen displayed a trend of higher concentration in patients with radiographic bone loss (RBL) ≥2 mm (P = 0.08). PICF TNF-α exhibited a significantly higher detection level in the CVD patients that is coincided with the local peri-implant inflammation. In addition, PICF MMP-8 was significantly higher in the RBL ≥2 mm sites than the healthy implants; whereas IL-1β, IL-8, MMP-8, and TIMP-2 proved to be the significant predictors for peri-implant disease. GCF TNF-α collected from patients with periodontitis was significantly associated with CVD cases., Conclusion: The augmented expression of local and systemic pro-inflammatory cytokines found in the current study supports the weak association between the chronic peri-implantitis with increasing severity and CVD., (© 2021 American Academy of Periodontology.)

Introduction: The purpose of the study was to explore the influence of leadership training programs on career development and to gain insight into the perspectives on faculty training programs according to the current US dental school deans., Methods: This prospective study analyzed the results of a questionnaire distributed to 67 active Deans of U.S dental schools using a survey instrument that explored the areas of leadership programs that were useful, the support mechanisms received from institutions, and the necessity to integrate formal leadership development programs into training programs for faculty and students., Results: Among 33 participants (49.3% participation rate) in the study, 97% of responders strongly or somewhat agreed that leadership development programs could improve the quality of leadership and administrative skills. The respondents found that the most useful areas in leadership training were conflict resolution, communication skills, organizational change, diversity, inclusion, and belonging. The findings highlighted that critical barriers to accessing leadership training are financial support and lack of protected time for faculty. The results also showed that 73% strongly or somewhat agreed that the leadership training should be integrated into the predoctoral program and 87% into the postdoctoral graduate programs., Conclusion: Participation in formal leadership development programs for faculty leaders in dental education is viewed as beneficial and could offer dental educators leadership training to better navigate the academic environment. The findings suggest the need to further explore the availability and effectiveness of leadership development opportunities for developing current and future educators and administrative leaders., (© 2022 American Dental Education Association.)

Background: This study assesses the association between peri-implantitis and cardiovascular diseases (CVD)., Methods: One hundred and twenty-eight patients with dental implants were recruited to evaluate the prevalence of peri-implantitis in patients with or without CVD (CVD group, n = 82, control group, n = 46, respectively). Diagnosis of peri-implantitis followed the 2017 World Workshop guidelines and the severity was defined as mild, moderate, and severe form when the radiographic bone loss (RBL) was <2, 2 to 4, and >4 mm. Multivariable logistic regression was performed to test the association between two diseases., Results: A trend of higher prevalence of peri-implantitis defined by detectable RBL beyond the physiologic bone remodeling was found in the CVD group (64.6%) when compared with the controls (56.5%). A significant higher prevalence (48.8%) of moderate to severe peri-implantitis was identified in CVD compared with controls(30.4%) with a significant crude association between moderate to severe peri-implantitis and CVD (odds ratio = 2.18, 95% CI, 1.02 to 4.67; P = 0.04). The CVD group had a trend of higher prevalence of deep pockets (≥7 mm) and higher numbers of sites with bleeding on probing  (>66%) when compared with controls (P > 0.05). However, after controlling for multiple confounders including age, hypertension, smoking, family history of heart attack, and periodontitis, the significant association was not found., Conclusions: CVD group had significantly higher prevalence of moderate to severe peri-implantitis (RBL ≥2 mm). The association between the two diseases did not exist after controlling multiple confounders for CVD. Future studies with a larger sample size controlling for the patient- and implant-related confounders are needed to better understand the link between peri-implantitis and CVD., (© 2021 American Academy of Periodontology.)

Objective: To describe long-term oral health outcomes and examine associations between sociodemographic factors, clinical characteristics, and markers of diabetes control on tooth loss in participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study., Research Design and Methods: Oral health outcomes related to tooth loss were reported at annual visits during EDIC years 22-26 (2015-2019). Generalized estimating equation models were used to assess the association of individual risk factors and tooth loss, over repeated time points., Results: A total of 165 (17%) participants with type 1 diabetes reported 221 oral health outcomes related to tooth loss over a five-year period. After controlling for age and current tobacco use, the presence of diabetic peripheral neuropathy was significantly associated with an increased odds of tooth loss (OR = 1.88, 95% CI 1.24, 2.87) while higher mean HDL/LDL cholesterol ratio was significantly associated with a decreased odds of tooth loss (OR = 0.87, 95% CI = 0.79, 0.97)., Conclusions: These findings suggest that diabetes-related complications, either resulting from or independent of poor glycemia, may be directly associated with oral health conditions, and support the need for individuals with type 1 diabetes and providers to implement lifestyle and medical interventions to reduce oral health risks., (Copyright © 2021. Published by Elsevier Inc.)

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn's disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

Few university-based regenerative medicine innovations in the dental, oral, and craniofacial (DOC) space have been commercialized and affected clinical practice in the United States. An analysis of the commercial translation literature and National Institute for Dental and Craniofacial Research's (NIDCR's) portfolio identified barriers to commercial translation of university-based DOC innovations. To overcome these barriers, the NIDCR established the Dental Oral Craniofacial Tissue Regeneration Consortium. We provide generalized strategies to inform readers how to bridge the "valley of death" and more effectively translate DOC technologies from the research laboratory or early stage company environment to clinical trials and bring needed innovations to the clinic. Three valleys of death are covered: 1) from basic science to translational development, 2) from translational technology validation to new company formation (or licensing to an existing company), and 3) from new company formation to scaling toward commercialization. An adapted phase-gate model is presented to inform DOC regenerative medicine teams how to involve regulatory, manufacturability, intellectual property, competitive assessments, business models, and commercially oriented funding mechanisms earlier in the translational development process. An Industrial Partners Program describes how to conduct market assessments, industry maps, business development processes, and industry relationship management methods to sustain commercial translation through the later-stage valley of death. Paramount to successfully implementing these methods is the coordination and collaboration of interdisciplinary teams around specific commercial translation goals and objectives. We also provide several case studies for translational projects with an emphasis on how they addressed DOC biomaterials for tissue regeneration within a rigorous commercial translation development environment. These generalized strategies and methods support innovations within a university-based and early stage company-based translational development process, traversing the many funding gaps in dental, oral, and craniofacial regenerative medicine innovations. Although the focus is on shepherding technologies through the US Food and Drug Administration, the approaches are applicable worldwide.

Additive manufacturing (AM) is the automated production of three-dimensional (3D) structures through successive layer-by-layer deposition of materials directed by computer-aided-design (CAD) software. While current clinical procedures that aim to reconstruct hard and soft tissue defects resulting from periodontal disease, congenital or acquired pathology, and maxillofacial trauma often utilize mass-produced biomaterials created for a variety of surgical indications, AM represents a paradigm shift in manufacturing at the individual patient level. Computer-aided systems employ algorithms to design customized, image-based scaffolds with high external shape complexity and spatial patterning of internal architecture guided by topology optimization. 3D bioprinting and surface modification techniques further enhance scaffold functionalization and osteogenic potential through the incorporation of viable cells, bioactive molecules, biomimetic materials and vectors for transgene expression within the layered architecture. These computational design features enable fabrication of tissue engineering constructs with highly tailored mechanical, structural, and biochemical properties for bone. This review examines key properties of scaffold design, bioresorbable bone scaffolds produced by AM processes, and clinical applications of these regenerative technologies. AM is transforming the field of personalized dental medicine and has great potential to improve regenerative outcomes in patient care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Latimer, Maekawa, Yao, Wu, Chen and Giannobile.)

The new classification of periodontal diseases recognizes the key role of the interdental clinical attachment for defining the periodontal status and the extent of disease severity. Regenerating interdental clinical attachment not only improves the prognosis of the tooth, but it also lessens the severity of the disease condition. This manuscript provides a state-of-the-art review on surgical reconstructive approaches for treating papillary deficiency associated with soft and hard tissue interproximal defects. Combination therapy of papilla preservation, connective tissue grafting, and coronally advanced flaps may result in regeneration of the intrabony defect coupled with root coverage. Future research highlighted here may have the potential, especially in combination approaches, to repair challenging interproximal soft and hard tissue deficiencies., (© 2020 American Academy of Periodontology.)

Rationale: The endemic of peri-implantitis affects over 25% of dental implants. Current treatment depends on empirical patient and site-based stratifications and lacks a consistent risk grading system. Methods: We investigated a unique cohort of peri-implantitis patients undergoing regenerative therapy with comprehensive clinical, immune, and microbial profiling. We utilized a robust outlier-resistant machine learning algorithm for immune deconvolution. Results: Unsupervised clustering identified risk groups with distinct immune profiles, microbial colonization dynamics, and regenerative outcomes. Low-risk patients exhibited elevated M1/M2-like macrophage ratios and lower B-cell infiltration. The low-risk immune profile was characterized by enhanced complement signaling and higher levels of Th1 and Th17 cytokines. Fusobacterium nucleatum and Prevotella intermedia were significantly enriched in high-risk individuals. Although surgery reduced microbial burden at the peri-implant interface in all groups, only low-risk individuals exhibited suppression of keystone pathogen re-colonization. Conclusion: Peri-implant immune microenvironment shapes microbial composition and the course of regeneration. Immune signatures show untapped potential in improving the risk-grading for peri-implantitis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aim: The use of recombinant human platelet-derived growth factor-BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and orthopedic bone defects and dermal wound healing. Many studies have investigated its regenerative potential in a variety of other oral clinical indications. The aim of this systematic review was to assess the efficacy, safety, and clinical benefit of recombinant human platelet-derived growth factor (rhPDGF) use for alveolar bone and/or soft tissue regeneration., Material and Methods: Comprehensive electronic and manual literature searches according to the PRISMA guidelines were performed to identify interventional and observational studies evaluating the regenerative applications of rhPDGF-BB. The primary outcomes were the safety, efficacy, and overall clinical benefit of rhPDGF use in oral regenerative procedures., Results: Sixty-three human clinical studies (mean ± SD follow-up period of 10.7 ± 3.3 mo) were included in the qualitative analysis. No serious adverse effects were reported in any of the 63 studies, aside from the postoperative complications routinely associated with surgical therapy. Use of rhPDGF was shown to be beneficial when combined with allografts, xenografts, and alloplasts (the latter tricalcium phosphate [β-TCP]) for the treatment of periodontal defects and gingival recession. The use of rhPDGF also led to favorable clinical outcomes when combined with allografts or xenografts for guided bone regeneration (GBR) and alveolar ridge preservation. While favorable clinical results support the use of the combination of rhPDGF plus allograft or xenograft for GBR, ARP, and sinus floor augmentation, current data support the use of rhPDGF and alloplasts (e.g., β-TCP) only in periodontal defects and gingival recession., Conclusions: Based on the clinical evidence, rhPDGF is safe and provides clinical benefits when used in combination with bone allografts, xenograft, or β-TCP for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for GBR and ARP (PROSPERO CRD42020142446)., Knowledge Transfer Statement: Clinicians should be aware that rhPDGF is a safe and effective approach for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for bone regeneration and alveolar ridge preservation. With consideration of cost and patient preference, this result could lead to more appropriate therapeutic decisions.

Aim: To describe the application of power Doppler Ultrasonography (US) for evaluating blood flow at implant and palatal donor sites following soft tissue augmentation with the connective tissue graft (CTG)., Materials and Methods: Five patients exhibiting a peri-implant soft tissue dehiscence received treatment with a coronally advanced flap and corresponding CTG. Power Doppler US was used for assessing blood volume at baseline, 1 week, 1 month, 6 months and 12 months post-surgery for assessing blood-flow dynamics at the implant and palatal donor sites. The speed-weighted and power-weighted colour pixel density (CPPD) were computed from colour velocity (CV) and colour power (CP), respectively., Results: A mean increase in CV of 199.25% was observed at the midfacial region of the implant sites after 1 week compared to baseline. CV and CP were increased in all sites at 1 week and 1 month. At 6 and 12 months, the mean CV appeared lower than baseline at the implant sites. CCPD was increased at the palatal donor sites and at the great palatine foramen areas at the 1-week and 1-month post-operative evaluations., Conclusions: Power Doppler US is a non-invasive and valuable tool for estimating tissue perfusion and CPPD variation during different phases of intra-oral soft tissue graft healing., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)