Search Results (658)

Background and Objectives: This study investigated the association between periodontal procedure intensity, serving as an indirect proxy for periodontal disease burden, and incident tinnitus in Korean adults. Materials and Methods: Using the Korean National Health Insurance Service–National Health Screening Cohort (2002–2019), we included adults aged ≥40 years who had a diagnosis of periodontal disease (International Classification of Diseases, 10th Revision [ICD-10] code K05), had undergone relevant periodontal treatment, and had available health-screening data. Because direct clinical periodontal measures were unavailable, participants were classified according to treatment intensity into: a mild procedure group (scaling or root planing only) and a moderate-to-severe procedure group (subgingival curettage, extraction, periodontal flap surgery, bone grafting, or guided tissue regeneration). Incident tinnitus was defined as an ICD-10 H93.1 diagnosis recorded during two or more outpatient visits to a neurology or otolaryngology department to improve diagnostic specificity. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models adjusted for demographic, socioeconomic, cardiometabolic, and behavioral factors. Results: Among 132,808 participants (76,844 mild; 55,964 moderate-to-severe), the incidence rate of tinnitus was higher in the moderate-to-severe group than in the mild group (4.38 vs. 3.87 per 1000 person-years). After adjustment, the moderate-to-severe group showed a significantly higher risk of tinnitus (HR 1.24, 95% CI 1.17–1.30). These associations were consistent across sex- and age-stratified analyses and in sensitivity analyses using stricter tinnitus definitions. Conclusions: Greater periodontal procedure intensity was associated with a modestly higher incidence of tinnitus in this nationwide cohort. Because procedure intensity serves only as an indirect surrogate for periodontal disease burden, and because auditory confounders and short-term procedure-related factors were unavailable, causality and a specific inflammatory mechanism cannot be established. Further studies incorporating direct periodontal measurements, audiological data, and prespecified lag-time analyses are warranted to confirm these findings. Full article

Guided bone regeneration (GBR) is a widely used clinical approach for managing bone defects associated with periodontal disease in dogs, employing barrier membranes to selectively direct tissue regeneration. The performance of these membranes is influenced by composition, structural design, and degradation behavior, which together determine biological responses and clinical outcomes. Biodegradable GBR membranes, fabricated from natural polymers, synthetic polymers, or composite materials, offer advantages over non-biodegradable membranes, including controlled resorption, elimination of secondary surgery, and the potential for delivery of bioactive agents. Preclinical studies in dogs have demonstrated that GBR membranes can promote periodontal regeneration, including bone and cementum formation and space maintenance; however, optimization of degradation behavior remains critical to align membrane resorption with tissue healing in some cases. Clinical studies in dogs with naturally occurring periodontal disease remain scarce, and only two biodegradable membranes (Ossiflex^® and Doxirobe^®) are commercially approved for veterinary use, while all others are applied off-label. These limitations highlight the need for more adaptable and cost-effective regenerative strategies, including membranes that can be customized to different defect sizes and multifunctional membranes incorporating bioactive agents that will offer an advanced regenerative potential and improved predictability in veterinary periodontal therapy. Full article

Periodontal organoid research remains underdeveloped, largely due to the lack of standardized fabrication protocols and multicellular constructs capable of reproducing epithelial–mesenchymal interactions relevant to periodontal biology. In particular, it remains unclear whether different spatial assembly strategies influence construct stability, multicellular organization, or early molecular behavior in periodontal three-dimensional (3D) systems. Therefore, this study aimed to develop and compare two different methods for generating dual-lineage 3D periodontal organoid-like constructs using human periodontal ligament cells (hPDL) and human gingival epithelial cells (hGEP). These strategies were selected to compare two biologically and technically distinct spatial configurations: bilayer assembly to partially mimic epithelial–connective tissue compartmentalization, and surface seeding as a simplified fabrication approach with potential advantages for reproducibility and workflow standardization. Both cell types were cultured in different media conditions (CnT-57, DMEM, and a 1:1 CnT-57/DMEM mixture) to determine compatibility for co-culture applications. Cell viability was assessed on days 1, 3, and 7 using the MTS assay. Constructs were produced in hyaluronic acid-based hydrogels using two strategies: Group 1–sequential photopolymerization of hPDL and hGEP layers to generate a bilayer construct; and Group 2—encapsulation of hPDL followed by direct seeding of hGEP onto the construct surface. Viability within constructs was evaluated on days 3 and 7 using the Live/Dead assay. Morphology was monitored using stereomicroscopy on days 0, 1, 3, and 7. Exploratory RNA sequencing was performed on day 7 to characterize transcriptomic profiles. All tested culture media maintained cellular viabilities above 70%, with no statistically significant differences among conditions (p > 0.05), indicating biocompatibility for both cell types. Group 1 exhibited viabilities of 86.54% ± 8.55% and 90.69% ± 7.88% on days 3 and 7, respectively, while Group 2 showed viabilities of 87.00% ± 9.58% and 88.08% ± 9.12%, with no significant intergroup differences (p > 0.05). Morphological analyses demonstrated preservation of construct integrity and progressive interaction between epithelial and mesenchymal compartments. Exploratory RNA sequencing revealed only subtle transcriptomic differences between assembly strategies. In conclusion, both methodologies successfully generated viable and structurally stable dual-lineage periodontal organoid-like constructs within a hyaluronic acid-based matrix. Comparison of these two assembly strategies demonstrates the feasibility of generating reproducible multicellular periodontal 3D models using distinct spatial configurations, establishing a proof-of-concept platform for future optimization toward periodontal disease modeling, regenerative studies, and advanced biofabrication applications. Full article

Tooth loss and bone resorption of the alveolar cavity caused by dental caries and periodontal disease remain major clinical challenges that compromise oral function. Tissue engineering approaches based on biocompatible scaffolds have emerged as promising strategies for bone regeneration; however, the influence of fabrication methods on scaffold performance remains unclear. This study developed hydroxyapatite/poly (lactic-coglycolic acid)/chitosan scaffolds (HAp/PLGA/CS) using freeze-drying and 3D-printing techniques and evaluated their physicochemical, biological, and biomechanical properties. The morphology, porosity, elemental composition, and mechanical properties of the scaffold were characterized, while the biocompatibility and osteogenic potential were evaluated using human dental pulp stem cells (hDPSCs). Finite element analysis (FEA) using COMSOL Multiphysics^® Version 6.2. was performed to evaluate scaffold behavior under simulated dental implant loading conditions. The 3D-printed scaffolds exhibited significantly higher cell viability than the freeze-dried scaffolds, reaching approximately 85% in the 50% filling group compared with 50% in the freeze-dried group. Microstructural analysis revealed interconnected hierarchical porosity, including macro-, micro-, and submicrometer scale pores. Although the 50% infill scaffold showed the highest cell viability, the 70% infill scaffold demonstrated the most favorable osteogenic profile, with enhanced expression of RUNX2 and OSX. Both types exhibited degradation profiles compatible with early bone regeneration. FEA simulations indicated that further mechanical optimization is required to improve load transfer and reduce deformation at the implant–scaffold interface. Overall, HAp/PLGA/CS scaffolds showed potential as experimental bioactive platforms for bone tissue engineering, with 3D-printed scaffolds providing greater architectural control and favorable early osteogenic responses. However, the translational relevance of these findings remains preliminary and requires validation through long-term degradation studies, in vivo bone regeneration and osseointegration models, cyclic mechanical testing, and implant fixation experiments. Full article

Background: Periodontitis is a chronic inflammatory disease characterized by a dysbiotic oral microbiome that leads to progressive periodontal tissue destruction. Current treatment primarily relies on scaling and root planing (SRP); however, this approach does not always completely eliminate pathogenic microorganisms or adequately modulate the host inflammatory response. Cold atmospheric plasma (CAP) generates reactive oxygen and nitrogen species (RONS) with potential antimicrobial, antibiofilm, and immunomodulatory properties, making it a promising adjunctive therapeutic modality for the management of periodontitis. Literature Search Strategy: A comprehensive literature search was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Embase to identify relevant studies published between January 2000 and June 2025. The search included in vitro, in vivo, and clinical studies evaluating the antimicrobial, immunomodulatory, and regenerative effects of CAP in periodontitis and related periodontal models. Reference lists of relevant articles were also manually screened to identify additional eligible studies. Objectives: This review aims to provide a comprehensive overview of the antimicrobial and immunomodulatory effects of CAP on periodontitis and to evaluate its potential as an adjunctive treatment modality. Furthermore, the review examines the regenerative potential and underlying mechanisms of CAP, while also addressing its clinical safety and biocompatibility. Key Findings: Preclinical evidence indicates that CAP reduces bacterial viability, disrupts biofilm architecture, and modulates host immune responses through RONS-mediated signaling pathways. In animal models of periodontitis, CAP has been shown to enhance markers of periodontal tissue repair, reduce the expression of pro-inflammatory cytokines, increase LC3-associated phagocytosis in macrophages, and accelerate wound healing. Clinical studies evaluating CAP as an adjunct to SRP have reported improvements in clinical attachment level (CAL) and reductions in the recolonization of periodontal pathogens. Nevertheless, substantial heterogeneity in CAP treatment parameters and a lack of long-term safety and efficacy data limit direct comparisons across studies and highlight the need for further well-designed clinical investigations. Conclusions: CAP appears to be a potentially useful adjunct to SRP in the management of periodontitis. Current preclinical evidence demonstrates significant antimicrobial, immunomodulatory, and regenerative effects; however, clinical evidence remains limited. Further high-quality clinical trials are required to validate these findings, establish standardized treatment protocols, optimize therapeutic parameters, and facilitate the development of regulatory frameworks for clinical implementation. Full article

Periodontitis, a chronic inflammatory disease driven by plaque biofilm, is a leading cause of tooth loss in adults worldwide. Effective treatment requires not only infection and inflammation control but, more critically, functional regeneration of the periodontal ligament, cementum, and alveolar bone. Periodontal regeneration, however, is a highly ordered, multi-stage biological cascade involving temporally coordinated phases of blood clot formation, inflammatory regulation, tissue formation, and remodeling. Conventional single-drug or mixed-delivery strategies cannot distinguish the distinct demands of each healing phase and fail to replicate this natural rhythm. Sequential controlled-release systems address this gap by delivering multiple bioactive agents (antimicrobials, immunomodulators, and growth factors) in a programmed order tailored to the healing cascade, enabling precise modulation of the periodontal microenvironment and orderly tissue regeneration. This review systematically summarizes advances in these systems, classifying material platforms into four categories: (1) diffusion-barrier and degradation-kinetics systems, including multilayer films, core–shell fibers, porous microspheres, and microneedle arrays; (2) stimuli-responsive systems triggered by pH, matrix metalloproteinases, reactive oxygen species, or exogenous physical stimuli; (3) cell and extracellular vesicle-based systems exploiting the inflammatory tropism of M2 macrophage-derived exosomes for targeted immune reprogramming; and (4) asymmetric structural designs achieving spatiotemporal coordination of physical and biochemical signals through hierarchical architectures. These systems follow an anti-infection/anti-inflammation first, osteogenesis later therapeutic logic, circumventing temporal antagonism among bioactive factors. However, significant challenges hinder clinical translation, including individualized prediction of release kinetics, long-term biocompatibility of carrier materials, material retention under dynamic oral conditions, translational limitations of animal models, and precise regulation of complex factor networks. Future progress will likely depend on multi-responsive and logic-gated systems, deeper integration of biotechnology and immunomodulation, personalized precision medicine, AI-driven material design, and robust clinical translational research. Full article

The tooth is a complex biological organ composed of multiple tissues, including enamel, dentine, cementum and pulp. However, dental disease and tooth loss due to periodontitis, caries, or trauma adversely affect most adults at some time in their lives. Tooth regeneration represents a shift in the dental paradigm from removal to repair to regeneration. Tooth regeneration is an extension of the broader field of regenerative medicine, aiming to restore a tissue defect to its original form and function by using biological substitutes to replace lost teeth or tooth tissue, providing a viable alternative to currently available clinical treatments. A full array of cell sources has been trialled for endodontic regeneration, following the basic premise of tissue engineering, including cells–scaffold–bioactive molecules. Several reports have documented dental pulp-like tissue regeneration, either in vitro or following the transplantation of stem cells. Tooth regeneration follows two unique approaches: cell transplantation and cell homing. Cell transplantation has been the predominant approach, whereas cell homing aims to achieve tissue repair and regeneration of the injury site through the chemotaxis of host endogenous cells. This narrative review explores therapeutically viable tooth regeneration approaches by contrasting cell transplantation and cell-to-scaffold methodologies focussing on the cell–scaffold–bioactive molecule triad. Full article

Material selection is crucial to hard tissue regeneration, and matching scaffold properties to those of the target tissue can improve clinical outcomes. This study compared the physicochemical, mechanical, and biological performance of fibrous scaffolds fabricated from polycaprolactone (PCL), polydioxanone (PDO), and gelatin methacryloyl (GelMA) for hard tissue regeneration. Polymeric fibers were produced by electrospinning, and their morphological, physical, and mechanical properties were characterized by scanning electron microscopy (SEM, n = 2), swelling and degradation analyses (n = 8), water contact angle measurements (n = 16), and tensile testing (n = 8). In addition, periodontal ligament stem cells (PDLSCs), alveolar bone marrow stem cells (aBMSCs), and dental pulp stem cells (DPSCs) were seeded onto the scaffolds to evaluate cell spreading (n = 4), viability (n = 8), and mineralized matrix formation (n = 6). Data were analyzed using one- or two-way ANOVA followed by appropriate post hoc tests (α = 5%). All polymers formed homogeneous fibrous scaffolds, with diameters within the nanoscale range. PDO and GelMA showed higher swelling than PCL, while PCL retained approximately 95% of its initial mass after three months. PCL and PDO showed higher elongation at break, tensile strength, and Young’s modulus than GelMA. Both PDO and GelMA displayed contact angles below 90°, with GelMA showing the lowest values. In vitro, all polymers were cytocompatible: PDO and GelMA enhanced DPSC viability at 7 days, whereas GelMA produced the highest viability for PDLSCs and aBMSCs at that time point. GelMA also promoted the highest mineralized matrix formation for DPSCs and PDLSCs, with no significant differences among polymers for aBMSCs. Overall, GelMA scaffolds promoted greater cell viability and mineralized matrix formation, while PCL and PDO provided superior mechanical properties, highlighting the importance of balancing biological and mechanical requirements when designing scaffolds for hard tissue regeneration. Full article

Periodontal diseases are highly prevalent conditions characterized by chronic inflammation, which leads to progressive destruction of tooth-supporting tissues. Conventional therapies, including scaling and root planing, grafting, and surgical procedures, are effective in controlling infection but show limited regenerative capacity. In this context, hydrogels—three-dimensional, highly hydrated polymeric biomaterials that mimic the extracellular matrix—have emerged as promising tools in periodontal regeneration. These materials can be engineered to modulate mechanical properties, porosity, and the delivery of bioactive molecules. Hydrogels can function as barrier membranes for guided tissue regeneration, scaffolds for stem cell support, and carriers for antimicrobial, anti-inflammatory, and osteogenic agents, enabling sustained and localized drug release. Recent studies have demonstrated their potential to inhibit bacterial biofilms, enhance osteogenic differentiation, and reduce inflammation in preclinical models. However, challenges remain regarding mechanical stability in the oral environment, controlled and sequential release of therapeutic agents, biocompatibility, and cost-effectiveness. Overall, hydrogels represent a promising adjunct in regenerative periodontal therapy, although further research is required to support their translation into routine clinical practice. Full article

Modulating the immune microenvironment has become an emerging strategy for promoting functional bone regeneration, identifying key therapeutic targets remains challenging. Our previous work showed that Nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing protein 5 (NLRC5) is involved in bone destruction associated with periodontitis, but its potential and mechanism in regulating bone tissue repair and regeneration have not been fully elucidated. A monocortical bone defect model was established in the mouse femur to assess the impact of NLRC5 on in situ bone healing and regeneration. Mouse bone marrow-derived mesenchymal stem cells (BMSCs) were isolated to evaluate the effects of NLRC5 on osteogenic differentiation, proliferation, and migration. RNA sequencing was used to explore the direct regulatory mechanism of NLRC5 on osteogenic differentiation of mouse BMSCs. Mass cytometry was employed to examine the effect of NLRC5 on the bone marrow immune microenvironment, followed by in vitro validation experiments. Loss of NLRC5 impaired the healing and regeneration of femoral bone defects in mice, and led to a high inflammatory state in the early stage of healing. The absence of NLRC5 inhibited the osteogenic differentiation ability of BMSCs, and could be restored by NLRC5 overexpression, which was achieved through activation of the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway. Mass cytometry data revealed that NLRC5 may serve as an important factor in maintaining the differentiation and maturation of regulatory T cells (Tregs). By modulating the levels of inflammatory cytokines, NLRC5 further influences the osteogenic differentiation of BMSCs. NLRC5 serves as a key regulator and promising candidate for bone repair. NLRC5 contributes to bone regeneration through a dual mechanism: it promotes BMSCs osteogenic differentiation, at least in part via the PI3K/AKT/β-catenin signaling pathway, and indirectly modulates the local immune microenvironment to facilitate bone repair. Full article

Background: Tooth root caries and periodontal tissue loss remain major challenges in elderly and periodontally compromised patients, while current restorative materials lack combined antibacterial and regenerative properties. Objective: The objective of this study was to develop a novel metformin-containing antibacterial composite for root cavity restorations to prevent recurrent caries and potentially promote periodontal tissue regeneration. Methods: Experimental composites contained 5% dimethylaminohexadecyl methacrylate (DMAHDM), varying metformin concentrations (2.5–15%), and glass fillers. Mechanical and antibacterial properties as well as cytocompatibility toward human periodontal ligament stem cells (hPDLSCs) were investigated. Results: The experimental composites achieved flexural strengths of 67.9 to 50.1 MPa (n = 6), significantly higher than (41.3 ± 3.4 MPa) of commercial control Vitremer (p < 0.05), while maintaining clinically acceptable elastic moduli of 3.7–3.1 GPa. Experimental composites achieved an 8-log reduction in Streptococcus mutans (S. mutans) biofilms and significantly reduced lactic acid production and metabolic activity compared to biofilms on commercial controls. The composite containing 15% metformin demonstrated acceptable cytocompatibility toward hPDLSCs under clinically relevant diluted conditions, matching commercial controls (p > 0.1). Conclusions: These findings suggest that this novel composite possesses potent antibacterial activity, acceptable cytocompatibility, and adequate mechanical properties, making it promising for multifunctional root caries restorations. Full article

Background: Collagen-based scaffolds are widely used in regenerative applications, where their structural organization and physicochemical stability are essential for clinical performance. This study aimed to evaluate the influence of hydration on the thermal behavior and microstructural characteristics of a collagen-based matrix (Mucoderm^®, Botiss Biomaterial GmbH, Zossen-Germany). Methods: Differential scanning calorimetry (DSC) was used to investigate thermal transitions in dry and rehydrated samples, while scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS) was employed to assess surface morphology and elemental composition; Results: The dry sample exhibited a broad endothermic transition at 87.8 °C, which shifted to higher temperatures upon rehydration, reaching 103.5 °C and 112.4 °C after 15 and 30 min, respectively. A corresponding increase in enthalpy values was also observed. SEM analysis revealed a heterogeneous surface morphology characterized by alternating compact and less dense regions, while EDS confirmed the predominance of carbon and oxygen with minor elements present in trace amounts; Conclusions: These findings indicate that hydration influences both the thermal response and structural organization of the scaffold, highlighting the role of water–matrix interactions in determining its physicochemical behavior. Full article

Periodontitis is a chronic inflammatory disease driven largely by dysregulated host responses that lead to destruction of periodontal tissues. Integrins are heterodimeric transmembrane receptors that regulate cell adhesion and bidirectional signaling in epithelial cells, immune cells, periodontal ligament fibroblasts, and osteoclasts. During disease progression, integrin-related responses may shift across overlapping molecular phases. Epithelial integrins such as α3β1 and α6β4 support barrier integrity, whereas α5β1 may facilitate microbial interaction and inflammatory signaling. β2 integrins and α4β1 contribute to leukocyte recruitment and inflammatory amplification, whereas increased α9β1-associated signaling and reduced αvβ6-mediated regulation of transforming growth factor β (TGF-β) may promote inflammatory persistence. Matrix-associated integrins, including α2β1 and α11β1, support extracellular matrix (ECM) organization and mechanotransduction, whereas αvβ3 cooperates with Receptor activator of nuclear factor kappa B ligand (RANKL) to promote osteoclast activity and alveolar bone resorption. Impaired β1 integrin-dependent signaling and potentially reduced αvβ5-associated efferocytosis may contribute to defective resolution and regeneration. Importantly, integrin expression, activation, and downstream signaling are distinct, and the strength of evidence varies among integrin subtypes. This review proposes a conceptual framework in which periodontitis reflects a dynamic imbalance in integrin-mediated processes that link inflammation, bone resorption, and regenerative failure, rather than being a direct equivalent of clinical periodontal stages or grades. Full article

Background/Objectives: Prepubertal localized aggressive periodontitis/LPP is an extremely rare but extremely fast-progressing form of periodontal disease involving systemically healthy children, starting in primary and mixed dentition. Our aim is to synthesize the data (January 2014–April 2026) on LPP progression description in systemically healthy children aged 2–13 years; clinical and biological responses to available treatment strategies, focusing on disease progression pattern, treatment efficacy and factors influencing treatment outcomes; and correlating findings with a report of a 24-month follow-up of a female prepubertal Caucasian patient during the primary and early stages of mixed dentition. Methods: A total of 489 studies were found after deduplication for the selected period. Due to the eligibility criteria, 9 studies plus another 10 contextual publications were included. Additionally, a 24-month follow-up of a previous LPP case was correlated. Results: LPP displayed rapid tissular destruction in primary dentition with risks to transfers to mixed and permanent dentition. The systemic antibiotic treatment reduced tissue loss, enabling fast periodontal regeneration. LPP is rare but severe, with a continuous biological trajectory, and with the window of opportunity remaining when the first symptoms appear. A few months (4–6 months) delay in diagnosis leads to irreversible tooth loss even in young patients with high biological healing potential. Conclusions: Systemic antibiotic treatment is mandatory in LPP/C-MIP cases from the primary dentition phase but does not reset host susceptibility. The Amoxicillin/Augmentin–Metronidazole association is recommended, with caution regarding dosage (adverse reactions). Periodontal gains are radiologically and clinically proven, but rebounding is possible. Full article

Background/Objectives: Peri-implant diseases, encompassing peri-implant mucositis and peri-implantitis, affect 43% and 18.8–23% of implant-bearing patients, respectively, representing significant clinical challenges in implant dentistry. While mechanical debridement remains foundational, biologically active materials offer promising adjunctive regenerative strategies. This narrative review synthesises current evidence regarding five biologically active materials: enamel matrix derivative (EMD), platelet-rich fibrin (PRF), fibroblast growth factor-2 (FGF-2), recombinant human platelet-derived growth factor-BB (rhPDGF-BB/GEM 21S^®), and polynucleotide–hyaluronic acid combinations (Regenfast^®). Methods: The relevant literature was identified using electronic databases, including MEDLINE, PubMed, Scopus, and Google Scholar. This review focused on clinical studies and randomised controlled trials with a minimum follow-up of six months investigating biologically active materials in peri-implant disease management. Material mechanisms, clinical efficacy, therapeutic limitations, and evidence quality were systematically evaluated. Attention was directed toward identifying genuine biological distinctions between peri-implant and periodontal disease contexts. Results: EMD demonstrates efficacy exclusively within multimodal surgical protocols, with isolated application yielding limited benefits. rhPDGF-BB shows superior periodontal regenerative capacity; however, dedicated peri-implantitis trials remain absent. FGF-2 exhibits paradoxical osteogenic suppression despite bone fill achievement, limiting peri-implant applicability. PRF and Regenfast^® demonstrate a mechanistically sound rationale yet lack substantive peri-implant disease validation. The critical findings revealed that peri-implant regeneration fundamentally differs from periodontal regeneration: implants lack periodontal ligament anatomy, rendering ligamentogenic differentiation-promoting agents biologically inappropriate. Conclusions: Contemporary biologically active materials demonstrate compelling periodontal efficacy yet remain inadequately validated for peri-implantitis management. This disparity reflects authentic biological distinctions rather than insufficient investigation. Until multicentre randomised controlled trials stratify efficacy across distinct peri-implant disease presentations, practitioners must prioritise evidence-based surgical fundamentals—meticulous decontamination, strategic grafting, and optimised wound healing—integrating biologically active materials judiciously within comprehensive, anatomy-respecting treatment protocols. Full article