{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:19:22Z","timestamp":1777407562875,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>Background\/Objectives: Peri-implant inflammatory complications remain a major cause of late implant failure and are closely associated with the condition of peri-implant soft tissues. Insufficient keratinized attached mucosa has been identified as a potential risk factor for peri-implant inflammation; however, morphological and immunohistochemical validation of soft tissue remodeling following corrective interventions remains limited. The aim of this study was to perform a morphological and immunohistochemical evaluation of a reproducible surgical approach for increasing keratinized attached mucosa around dental implants. Methods: A comparative clinical\u2013morphological study included 25 patients undergoing implant-supported prosthetic treatment. Patients were divided into a control group (standard prosthetic protocol without soft tissue augmentation, n = 10) and a study group (soft tissue correction using a previously developed technique, n = 15). Punch biopsies of peri-implant mucosa were obtained at baseline and prior to definitive prosthetic restoration. Histological examination and immunohistochemical analysis were performed using the semi-quantitative Astaldi\u2013Verga method. Expression of inflammatory markers (MPO, CD3, CD20, CD68), vascular marker CD31, and remodeling markers MMP-9 and TIMP-2 was evaluated. Data were analyzed using the Mann\u2013Whitney U test (p &lt; 0.05). Results: The study group demonstrated significantly lower expression of inflammatory markers, including MPO, CD68, CD3, and CD20 (p &lt; 0.001), and reduced MMP-9 expression (p = 0.001) compared with controls. The MMP-9\/TIMP-2 balance was more favorable in the study group, suggesting more regulated extracellular matrix remodeling. Histologically, the control group exhibited epithelial disruption and microcirculatory alterations, whereas the study group showed preserved epithelial architecture and reduced inflammatory infiltration. Conclusions: Morphological and immunohistochemical assessment suggests that soft tissue correction of keratinized mucosa deficiency may be associated with more favorable early peri-implant soft tissue characteristics, including reduced inflammatory activity and modulation of matrix remodeling. Immunohistochemical markers such as MMP-9 and TIMP-2 may provide additional insight into early soft tissue integration around dental implants. However, these findings should be interpreted with caution due to the exploratory design and short follow-up period.<\/jats:p>","DOI":"10.3390\/dj14050256","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:55:39Z","timestamp":1777370139000},"page":"256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Surgical Correction of Keratinized Mucosa Deficiency Around Dental Implants: A Clinical, Histological and Immunohistochemical Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Emil K.","family":"Khabirov","sequence":"first","affiliation":[{"name":"Department of Prosthetic Dentistry, Kazan State Medical University, Kazan 420012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulshat T.","family":"Saleeva","sequence":"additional","affiliation":[{"name":"Department of Prosthetic Dentistry, Kazan State Medical University, Kazan 420012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2593-4478","authenticated-orcid":false,"given":"Dmitry E.","family":"Tsyplakov","sequence":"additional","affiliation":[{"name":"General Pathology Department, Kazan State Medical University, Kazan 420012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rinat A.","family":"Saleev","sequence":"additional","affiliation":[{"name":"Department of Prosthetic Dentistry, Kazan State Medical University, Kazan 420012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laysan R.","family":"Shakirova","sequence":"additional","affiliation":[{"name":"Department of Prosthetic Dentistry, Kazan State Medical University, Kazan 420012, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S313","DOI":"10.1002\/JPER.17-0739","article-title":"Peri-implant Diseases and Conditions: Consensus Report of Workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Berglundh","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S230","DOI":"10.1111\/jcpe.12952","article-title":"Peri-implant Health","volume":"45","author":"Araujo","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","first-page":"13","article-title":"Significance of Peri-Implant Keratinised Mucosa on Implant Health: An Umbrella Systematic Review with Evidence Mapping and Quantitative Meta-Meta-Analysis","volume":"18","author":"Sabri","year":"2025","journal-title":"Int. J. Oral Implantol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1097\/ID.0000000000000483","article-title":"Effect of the Keratinized Mucosa Width on the Health Status of Periimplant and Contralateral Periodontal Tissues: A Cross-Sectional Study","volume":"25","author":"Ueno","year":"2016","journal-title":"Implant. Dent."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1563\/aaid-joi-D-25-00049","article-title":"The Significance of Keratinized Mucosa on Implant Health: An Umbrella Review","volume":"51","author":"Fathi","year":"2025","journal-title":"J. Oral Implantol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1111\/clr.13381","article-title":"Influence of the Keratinized Mucosa on the Stability of Peri-implant Tissues and Brushing Discomfort: A 4-year Follow-up Study","volume":"29","author":"Perussolo","year":"2018","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/clr.13114","article-title":"Effects of Soft Tissue Augmentation Procedures on Peri-implant Health or Disease: A Systematic Review and Meta-analysis","volume":"29","author":"Thoma","year":"2018","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/clr.13798","article-title":"Soft Tissue Management at Implants: Summary and Consensus Statements of Group 2. The 6th EAO Consensus Conference 2021","volume":"32","author":"Thoma","year":"2021","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"913","DOI":"10.11607\/prd.5063","article-title":"A Biologically Driven Concept to Design the Emergence Profile Around Dental Implants: Surgical and Prosthetic Considerations to Optimize Hard and Soft Tissue Integration","volume":"41","author":"Fabbri","year":"2021","journal-title":"Int. J. Periodontics Restor. Dent."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/JPER.24-0144","article-title":"The Influence of Prosthetic Designs on Peri-Implant Bone Loss: An AO\/AAP Systematic Review and Meta-Analysis","volume":"96","author":"Lin","year":"2025","journal-title":"J. Periodontol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.prosdent.2025.03.027","article-title":"Influence of Abutment Shape on Early Peri-Implant Marginal Bone Loss and Crestal Bone Remodeling: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"135","author":"Liu","year":"2026","journal-title":"J. Prosthet. Dent."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/clr.13759","article-title":"Linear and Profilometric Changes of the Mucosa Following Soft Tissue Augmentation in the Zone of Aesthetic Priority: A Systematic Review and Meta-analysis","volume":"32","author":"Raghoebar","year":"2021","journal-title":"Clin. Oral Implant. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1111\/j.1600-051X.2009.01460.x","article-title":"Clinical Evaluation of a New Collagen Matrix (Mucograft\u00ae Prototype) to Enhance the Width of Keratinized Tissue in Patients with Fixed Prosthetic Restorations: A Randomized Prospective Clinical Trial","volume":"36","author":"Sanz","year":"2009","journal-title":"J. Clin. Periodontol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1590\/S0103-64402009000300003","article-title":"Clinical Evaluation of a Dermic Allograft in Procedures to Increase Attached Gingiva Width","volume":"20","author":"Vieira","year":"2009","journal-title":"Braz. Dent. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ardila, C.M., Pineda-V\u00e9lez, E., and Vivares-Builes, A.M. (2025). Transcriptomic and Metagenomic Biomarkers in Peri-Implantitis: A Systematic Review, Diagnostic Meta-Analysis, and Functional Meta-Synthesis. Med. Sci., 13.","DOI":"10.3390\/medsci13030187"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Luchian, I., Goriuc, A., Sandu, D., and Covasa, M. (2022). The Role of Matrix Metalloproteinases (MMP-8, MMP-9, MMP-13) in Periodontal and Peri-Implant Pathological Processes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031806"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25854","DOI":"10.1074\/jbc.M109.033472","article-title":"Neutrophil MMP-9 Proenzyme, Unencumbered by TIMP-1, Undergoes Efficient Activation in Vivo and Catalytically Induces Angiogenesis via a Basic Fibroblast Growth Factor (FGF-2)\/FGFR-2 Pathway","volume":"284","author":"Ardi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.joen.2009.10.030","article-title":"Matrix Metalloproteinase Expression in Teeth with Apical Periodontitis Is Differentially Modulated by the Modality of Root Canal Treatment","volume":"36","author":"Kapila","year":"2010","journal-title":"J. Endod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/odi.12159","article-title":"Matrix Metalloproteinases and Periodontal Diseases","volume":"20","author":"Sapna","year":"2014","journal-title":"Oral Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1159\/000205237","article-title":"The Glycogen Content of the Cells of Lymphatic Leukaemia","volume":"17","author":"Astaldi","year":"2009","journal-title":"Acta Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Roi, C., Gaje, P.N., Ceau\u0219u, R.A., Roi, A., Rusu, L.C., Boia, E.R., Boia, S., Luca, R.E., and Rivi\u0219, M. (2022). Heterogeneity of Blood Vessels and Assessment of Microvessel Density-MVD in Gingivitis. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102758"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Checchi, V., Maravic, T., Bellini, P., Generali, L., Consolo, U., Breschi, L., and Mazzoni, A. (2020). The Role of Matrix Metalloproteinases in Periodontal Disease. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17144923"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huang, W.-C., Sala-Newby, G.B., Susana, A., Johnson, J.L., and Newby, A.C. (2012). Classical Macrophage Activation Up-Regulates Several Matrix Metalloproteinases through Mitogen Activated Protein Kinases and Nuclear Factor-\u03baB. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042507"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1111\/jcpe.14025","article-title":"Elevated Neutrophil Extracellular Trap Levels in Periodontitis: Implications for Keratinization and Barrier Function in Gingival Epithelium","volume":"51","author":"Cui","year":"2024","journal-title":"J. Clin. Periodontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"96","DOI":"10.5051\/jpis.2010.40.2.96","article-title":"Clinical Evaluation of a Collagen Matrix to Enhance the Width of Keratinized Gingiva around Dental Implants","volume":"40","author":"Lee","year":"2010","journal-title":"J. Periodontal Implant. Sci."}],"container-title":["Dentistry Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-6767\/14\/5\/256\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:37:57Z","timestamp":1777372677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-6767\/14\/5\/256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["dj14050256"],"URL":"https:\/\/doi.org\/10.3390\/dj14050256","relation":{},"ISSN":["2304-6767"],"issn-type":[{"value":"2304-6767","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]}}}