About

Georgios Kotsakis is an Assistant Dean for Clinical Research and Director of Research at Rutgers School of Dental Medicine, within the Department of Oral Biology. He is a dual-trained clinician scientist whose clinical interests focus on the management of implant complications and alveolar bone regenerative surgeries, utilizing evidence-based clinical and surgical strategies. His primary research centers on translational studies investigating the complex pathogenetic mechanisms of peri-implant inflammation, aiming to develop prevention and therapy methods. Dr. Kotsakis has led and participated in multi-center clinical trials targeting bacterial, host, and environmental factors affecting oral health. At Rutgers, he directs the RSDM Clinical Research Center, funded by the NIH, which conducts translational research to examine biological mechanisms underlying peri-implant bone loss and to identify druggable targets for improving the success of dental and biomedical implants.

Research topics

• Information Retrieval
• Computer Science
• Data science
• Psychology

Selected publications

• Effects of Periodontal‐Specific Exosomes and <scp>rhBMP2</scp> on Osteogenic Behaviour and Differentiation of <scp>BMSCs</scp>

  Journal of Cellular and Molecular Medicine · 2026-01-28 · 1 citations

  articleOpen accessSenior author

  Growth factors, including recombinant human bone morphogenetic protein-2 (rhBMP2), have been clinically utilised for large bone augmentation with good outcomes. Nevertheless, long-term healing, swelling, safety concerns, and high cost limit their use. Exosomes, nanoscale extracellular vesicles, have emerged as promising regenerative alternatives. This study assessed the osteogenic potential of periodontal-specific exosomes (Px) on bone marrow mesenchymal stem cells (BMSCs) compared to rhBMP2. Px were morphologically characterised by TEM and quantified via BCA assay. BMSCs were treated with Px at 1:10, 1:50, and 1:100 dilutions (100, 20, and 10 μg/mL) and compared to rhBMP2 (100 ng/mL). Px uptake was evaluated using PKH26 labeling. Functional assays included viability, migration, alkaline phosphatase (ALP) activity, alizarin red (ARS) mineralization, collagen, osteocalcin secretion, and RT-PCR analysis of osteogenic genes. Px exhibited spheroidal to cup-shaped morphology and internalisation in BMSCs up to 18 days. Compared to rhBMP2, Px promoted viability (1.14-fold), migration (1.78-fold) up to 1.14 and 1.78-fold, ALP (1.48-, 4.11-fold), ARS (1.43-, 14.71-fold), collagen (1.40-, 3.58-fold), and osteocalcin (1.86-, 5.2-fold). Gene expression demonstrated significant upregulation of ALP (1.73-fold), RUNX2 (1.70-fold), OCN (1.36-fold), and OPN (1.35-fold). Overall, Px significantly enhanced BMSC osteogenesis compared to rhBMP2, highlighting their potential as a cell-free nanotherapeutic in bone tissue engineering.

  PublisherOA PDFDOI

• Effects of Periodontal-Specific Exosomes and rhBMP2 on Osteogenic Behaviour and Differentiation of BMSCs.

  Open Access CRIS of the University of Bern · 2026-01-31

  articleOpen accessSenior author

  Growth factors, including recombinant human bone morphogenetic protein-2 (rhBMP2), have been clinically utilised for large bone augmentation with good outcomes. Nevertheless, long-term healing, swelling, safety concerns, and high cost limit their use. Exosomes, nanoscale extracellular vesicles, have emerged as promising regenerative alternatives. This study assessed the osteogenic potential of periodontal-specific exosomes (Px) on bone marrow mesenchymal stem cells (BMSCs) compared to rhBMP2. Px were morphologically characterised by TEM and quantified via BCA assay. BMSCs were treated with Px at 1:10, 1:50, and 1:100 dilutions (100, 20, and 10 μg/mL) and compared to rhBMP2 (100 ng/mL). Px uptake was evaluated using PKH26 labeling. Functional assays included viability, migration, alkaline phosphatase (ALP) activity, alizarin red (ARS) mineralization, collagen, osteocalcin secretion, and RT-PCR analysis of osteogenic genes. Px exhibited spheroidal to cup-shaped morphology and internalisation in BMSCs up to 18 days. Compared to rhBMP2, Px promoted viability (1.14-fold), migration (1.78-fold) up to 1.14 and 1.78-fold, ALP (1.48-, 4.11-fold), ARS (1.43-, 14.71-fold), collagen (1.40-, 3.58-fold), and osteocalcin (1.86-, 5.2-fold). Gene expression demonstrated significant upregulation of ALP (1.73-fold), RUNX2 (1.70-fold), OCN (1.36-fold), and OPN (1.35-fold). Overall, Px significantly enhanced BMSC osteogenesis compared to rhBMP2, highlighting their potential as a cell-free nanotherapeutic in bone tissue engineering.

  PublisherDOI

• Protocol for spectrophotometric determination of titanium microparticles in biological samples via Ti(IV)-H2O2 reactions

  STAR Protocols · 2026-04-21

  articleOpen accessSenior author

  ) chromogenic reaction and validating detection accuracy. This protocol provides an accessible, scalable technique for quantifying Ti particles in laboratories with limited access to advanced analytical instrumentation.

  PublisherDOI

• Peri-implant disease pathogenesis animal models: Consensus report of Workgroup 1 of the IADR Implantology Research Group Best Evidence Consensus Symposium on Peri-Implant Disease and Its Treatment.

  Open Access CRIS of the University of Bern · 2026-01-14

  articleOpen access1st authorCorresponding

  Background The pathogenesis and etiology of peri-implantitis demand a deeper understanding to lead to successful treatment modalities. Animal models of peri-implantitis pathogenesis offer unique insights but their translational impact requires consideration of implant biomaterials science. This systematic review, sanctioned by the International Association for Dental Research (IADR) Implantology Research Group, aimed to systematically review animal models in peri-implant disease research. Experts deliberated on merits, limitations, and optimization of various models to guide researchers in selecting suitable platforms for investigations.Methods A pre-registered review (ID: CRD42023399976) was performed guided by the PICO question: Population (P): Laboratory animals with dental implants or surrogate biomaterials placed in the oral cavity; Intervention (I): Induction of peri-implant inflammation; Control (C): Animals without induced inflammation or those subjected to a placebo treatment only; Outcome (O): Parameters including bone loss, histopathology of peri-implant tissues, tissue inflammatory response, and microbiological outcomes.Results Searches identified 158 articles, with 96 meeting inclusion criteria following a 2-step systematic review (inter-reviewer agreement: kappa = 0.72; 0.68, respectively for each phase). Most studies were on large animal models, mainly dogs (n = 66); the majority employed ligature-induced peri-implant defect models. These models often reported delayed implant placement after teeth extraction followed by active breakdown via ligatures of various types, and a chronicity progression period without the ligatures to assimilate chronic inflammatory lesions. Primate studies (n = 6) were published from the late 1990s to early 2000s. Murine models in mice (n = 16) focused on disease establishment and biomolecular aspects, while rat models (n = 6) addressed diabetes, xerostomia, and inflammation suppression. Murine models invariably required custom implant devices due to volume limitations, which often did not have implant surface modifications limiting their translational potential. Mini-pig models (n = 2) delved into microbiological shifts and the impact of soft tissue management on peri-implant infection.Conclusion Comprehensive overview of animal models in peri-implant disease research offered insights into their strengths, challenges, and findings. The ongoing shift toward non-animal alternatives and future horizons in peri-implantitis research is highlighted.Plain Language Summary This commissioned systematic review provides a comprehensive overview of animal models in peri-implant disease research, offering insights into their strengths, challenges, and findings. Further, this article summarizes the consensus proceedings of the IADR IRG Peri-Implantitis Best Evidence Consensus and provides guidance for future use of animals in peri-implantitis research.

  PublisherDOI

• Implant-derived titanium particles impair macrophage bacterial clearance via TRPC1 and lysosomal dysfunction

  PNAS Nexus · 2026-03-21

  articleOpen accessSenior author

  Abstract Peri-implantitis (PI) is a treatment-resistant inflammatory condition that affects millions of patients with dental implants, leading to destructive loss of jawbone, implant failure, and escalating healthcare costs. It is classically attributed to bacterial biofilms; however, unlike periodontitis, it frequently progresses despite resolution of infection with standard antimicrobial therapy, suggesting a critical gap in our understanding of host-response dysfunction. Here, we identify implant-derived titanium particles (i-TiPs) as a persistent, abiotic pathogenic co-factor that impairs macrophage immune function by disrupting TRPC1-dependent Ca2+ signaling and lysosomal integrity. Mechanistically, we demonstrate that i-TiPs inhibit bacterial clearance by triggering dysregulated Ca2+ influx and lysosomal alkalinization, leading to defective phagolysosome maturation and increased inflammatory cytokine release. In vivo, TRPC1 knockout (trpc1−/−) mice challenged with i-TiPs maintain effective bacterial clearance, exhibit reduced cytokine responses, and develop significantly smaller titanium-mediated abscesses. These findings uncover a particle-induced host immune failure mechanism that explains PI's clinical resistance to antibiotics and underscore the need for adjunctive host modulation strategies beyond antimicrobial treatments to restore immune competence. In summary, this study demonstrates that i-TiPs fundamentally alter the host immune response to bacteria and act as a critical co-factor in the pathogenesis of PI. More broadly, our work positions the peri-implant microenvironment as a high-impact model system for investigating how abiotic exposomes, such as medical implant debris, alter host–microbe interactions and immune regulation in chronic disease.

  PublisherDOI

• Peri‐implant disease pathogenesis animal models: Consensus report of Workgroup 1 of the IADR Implantology Research Group Best Evidence Consensus Symposium on Peri‐Implant Disease and Its Treatment

  Journal of Periodontology · 2026-01-14

  articleOpen access1st authorCorresponding

  BACKGROUND: The pathogenesis and etiology of peri-implantitis demand a deeper understanding to lead to successful treatment modalities. Animal models of peri-implantitis pathogenesis offer unique insights but their translational impact requires consideration of implant biomaterials science. This systematic review, sanctioned by the International Association for Dental Research (IADR) Implantology Research Group, aimed to systematically review animal models in peri-implant disease research. Experts deliberated on merits, limitations, and optimization of various models to guide researchers in selecting suitable platforms for investigations. METHODS: A pre-registered review (ID: CRD42023399976) was performed guided by the PICO question: Population (P): Laboratory animals with dental implants or surrogate biomaterials placed in the oral cavity; Intervention (I): Induction of peri-implant inflammation; Control (C): Animals without induced inflammation or those subjected to a placebo treatment only; Outcome (O): Parameters including bone loss, histopathology of peri-implant tissues, tissue inflammatory response, and microbiological outcomes. RESULTS: Searches identified 158 articles, with 96 meeting inclusion criteria following a 2-step systematic review (inter-reviewer agreement: kappa = 0.72; 0.68, respectively for each phase). Most studies were on large animal models, mainly dogs (n = 66); the majority employed ligature-induced peri-implant defect models. These models often reported delayed implant placement after teeth extraction followed by active breakdown via ligatures of various types, and a chronicity progression period without the ligatures to assimilate chronic inflammatory lesions. Primate studies (n = 6) were published from the late 1990s to early 2000s. Murine models in mice (n = 16) focused on disease establishment and biomolecular aspects, while rat models (n = 6) addressed diabetes, xerostomia, and inflammation suppression. Murine models invariably required custom implant devices due to volume limitations, which often did not have implant surface modifications limiting their translational potential. Mini-pig models (n = 2) delved into microbiological shifts and the impact of soft tissue management on peri-implant infection. CONCLUSION: Comprehensive overview of animal models in peri-implant disease research offered insights into their strengths, challenges, and findings. The ongoing shift toward non-animal alternatives and future horizons in peri-implantitis research is highlighted. PLAIN LANGUAGE SUMMARY: This commissioned systematic review provides a comprehensive overview of animal models in peri-implant disease research, offering insights into their strengths, challenges, and findings. Further, this article summarizes the consensus proceedings of the IADR IRG Peri-Implantitis Best Evidence Consensus and provides guidance for future use of animals in peri-implantitis research.

  PublisherDOI

• Biomaterials for resolution of peri‐implantitis: Consensus report of Workgroup 2 of the IADR Implantology Research Group Best Evidence Consensus Symposium on Peri‐Implant Disease and Its Treatment

  Journal of Periodontology · 2026-03-30

  articleOpen accessSenior author

  BACKGROUND: Peri-implantitis is a destructive disease affecting the tissues surrounding dental implants. Biomaterials may be applied during surgical treatment to reconstruct bony defects and support soft tissue healing. However, current evidence is unclear if these treatments increase the likelihood of peri-implantitis resolution. METHODS: A systematic review and meta-analysis was performed on randomized controlled trials (RCTs) comparing surgical treatment with addition of reconstructive biomaterials (intervention) versus surgical treatment of peri-implantitis alone (comparison) with follow-up periods of at least 12 months. Resolution of peri-implantitis, defined as a reduction of probing pocket depth (PPD) to ≤5 mm, absence bleeding on probing (BOP), and stable or decreasing radiographic defect level (RDL), was selected as the primary outcome. Secondary outcomes included RDL reduction, buccal mucosal recession (REC), and patient-related outcome measures (PROMs). Risk of bias and quality of evidence were calculated using established guidelines. RESULTS: : 85%) and for REC, a WMD of -0.38 (95% CI -0.66, -0.11) was found, both in favor of the intervention. Analysis of the heterogeneity affecting RDL identified a positive effect on RDL when hydrogen peroxide but not rotary titanium brushes were used as an adjunct for implant surface debridement. CONCLUSION: Current evidence suggests that incorporating reconstructive biomaterials into surgical treatment may not definitively enhance the likelihood of peri-implantitis disease resolution. However, this lack of effect may be due to other factors such as implant surface treatments which may also affect clinical outcomes. Overall, this work highlights the critical need for standardizing the reporting of composite outcomes for the resolution of peri-implantitis disease and controlling for implant surface treatment effects when assessing reconstructive biomaterials. PLAIN LANGUAGE SUMMARY: Peri-implantitis is a destructive disease affecting tissues around dental implants. We studied whether adding reconstructive biomaterials (i.e., biomaterials used to improve the likelihood of new bone formation or bone defect fill) to surgical treatments improves the clinical condition, meaning no further bone loss, probing pocket depths (PPD) ≤5 mm, and no bleeding on probing (BOP). We reviewed randomized controlled trials (RCTs) comparing surgery with biomaterials to surgery alone with at least 12 months of follow-up. The main outcomes measured were PPD reduction, absence of BOP, and radiographic defect level (RDL). Secondary outcomes included RDL change, buccal mucosal recession (REC), and patient-related outcomes (PROMs). Seven studies with 402 patients and 405 implants were analyzed. Due to variations in outcome reporting, it was challenging to compare the effectiveness of treatments. However, some individual analyses showed a small improvement in PPD and BOP with biomaterials. For RDL reduction, biomaterials showed better results, but with significant variability. REC also improved slightly with biomaterials. The analysis also suggested that using hydrogen peroxide, but not rotary titanium brushes, for implant cleaning could positively affect bone levels. The study concluded that adding biomaterials to surgical treatment does not definitively improve peri-implantitis resolution, possibly due to other factors like implant surface treatments. This study emphasized the need for standardized reporting and considering these factors in future research.

  PublisherDOI

• Periodontitis and quality of life in adults with cystic fibrosis - A pilot cross-sectional study

  Community dental health · 2025-12-03

  article

  BACKGROUND: Attributes of cystic fibrosis (CF) can increase one's risk of developing periodontitis, and both CF and periodontitis are known to impact health-related quality of life (HRQoL). In this hypothesis-generating pilot study, our goals were to assess if periodontitis is associated with lower HRQoL for adults with CF and to identify sociodemographic, medical, and dental factors associated with HRQoL. METHODS: = 32). HRQoL was assessed in two ways: (1) Oral health-related quality of life (OHRQoL) based on the Oral Health Impact Profile 14 (OHIP-14); and (2) CF-related quality of life (CFRQoL) based on the Cystic Fibrosis Questionnaire-Revised (CFQ-R). We used the Mann-Whitney test to assess for differences in median scores of OHIP-14 and CFQ-R domains by periodontitis status. We used the Mann-Whitney test, the Kruskal-Wallis test, and the Spearman rank correlation to identify factors associated with HRQoL. RESULTS: The median age of participants was 30 years, 63% were female, and 97% were white. Median OHIP-14 and CFQ-R domain scores did not differ significantly by periodontitis status. There were no significant differences in the OHIP-14 or CFQ-R domain scores for adults with CF by periodontitis severity. Low socioeconomic status (SES), anxiety, and depression were associated with significantly worse domain scores for both HRQoL measures. CONCLUSIONS: Periodontitis in adults with CF was not associated with HRQoL, but markers of low SES and poor mental health were associated with lower HRQoL, including OHRQoL. These findings are preliminary and should be interpreted within the context of this study population comprised of higher-income adults with CF. Future studies should further examine potential disparities in HRQoL for a more socioeconomically diverse individuals with CF.

  PublisherDOI

• 3D Peri-Implant Epi-Mucosa-on-a-Chip Reveals Alterations in Epithelial Barrier Function Mediated by Host-Bacteria-Biomaterial Interactions

  ACS Biomaterials Science & Engineering · 2025-11-12 · 5 citations

  articleOpen access

  Peri-implantitis is characterized by disruption of the epithelial barrier at the implant–mucosa interface, driven by complex interactions between mechanical, microbial, and material factors. Histological and immunohistochemical analysis of human peri-implant and periodontal tissues revealed significant epithelial abnormalities specific to peri-implantitis, which indicated compromised barrier integrity. Specifically, peri-implant tissues had increased intercellular edema, inflammatory infiltration, and marked loss of junctional proteins E-cadherin and ZO-1. To further investigate these findings in a controlled environment, we developed a novel 3D Peri-implant Epi-mucosa-on-a-chip model incorporating clinically relevant titanium surfaces, hydrostatic pressure, and bacterial challenge to mimic peri-implant crevicular fluid dynamics and disease pathogenesis. Using this microfluidic platform, we demonstrated that untreated titanium surfaces significantly increased epithelial leakiness and disrupted the localization of junctional proteins, such as E-cadherin. In contrast, acid-etched titanium with defined microroughness restored barrier function and preserved junctional integrity. High hydrostatic pressure, mimicking inflammatory mechanical stress, independently impaired epithelial cohesion, whereas the combination of Porphyromonas gingivalis (P. gingivalis) and implant-derived titanium microparticles (i-TiPs) synergistically exacerbated barrier breakdown. i-TiPs also altered matrix architecture and stiffness, further compromising epithelial integrity and potentiating bacterial damage. These results underscore the critical role of implant surface properties and the mechanical microenvironment in modulating host barrier responses and highlight the utility of our 3D model in elucidating the mechanobiology of peri-implantitis. This platform may pave the way for the development of new therapeutic strategies against peri-implantitis, aimed at preserving epithelial sealing and preventing disease progression.

  PublisherDOI

• Complete genome sequence of <i>Veillonella parvula</i> strain PK1910

  Microbiology Resource Announcements · 2025-02-25

  articleOpen access

  ABSTRACT Here, we announce the complete genome sequence of Veillonella parvula strain PK1910, obtained from a frozen stock. The genome is composed of one closed contig with a length of 2,213,486 bp, resulting in 98.0× coverage containing 1,979 protein-coding genes, with a GC content of 38.74%.

  PublisherDOI

Frequent coauthors

• Dan J. Stein

  South African Medical Research Council

  102 shared

• Ai Koyanagi

  Instituto de Salud Carlos III

  97 shared

• Nancy Fullman

  88 shared

• Rakhi Dandona

  University of Washington

  88 shared

• Christopher J L Murray

  University of Washington

  88 shared

• P A Mahesh

  JSS Medical College and Hospital

  87 shared

• Lalit Dandona

  87 shared

• Chuanhua Yu

  87 shared

Education

• DDS, Developmental and Surgical Sciences

  University of Minnesota

  2015