Periodontitis is a highly prevalent, irreversible inflammatory disease characterized by the destruction of tooth-supporting tissues, eventually leading to tooth loss. Conventional treatment involves the mechanical removal of the subgingival biofilm, which is a major cause of gingival inflammation. However, the inaccessibility of deep-seated polymicrobial biofilms limits its effectiveness. Despite the adjunct use of systemic antimicrobials, their low site-specific bioavailability and systemic side effects remain concerns. Local drug administration offers a targeted alternative. However, the dynamic oral environment, which is characterized by continuous salivary and gingival crevicular fluid flow, poses challenges in maintaining therapeutic drug levels. Drug delivery systems (DDSs) provide technical solutions to overcome these limitations. With advancements in materials science and nanotechnology, diverse local DDS (LDDS) formulations tailored for periodontal applications have been developed. While traditionally focused on infection control, the application of LDDSs has expanded beyond antimicrobial therapy. Increasing attention has been paid to LDDS-based regenerative strategies, which aim to overcome the limitations of conventional regenerative therapies. This review aims to provide a comprehensive overview of the current and emerging DDS strategies in periodontal therapy, focusing on their applications in infection management and bone regeneration and discussing their limitations and prospects for clinical translation.

Background: Advanced platelet-rich fibrin (A-PRF) is used in periodontal regeneration due to its autologous fibrin matrix and bioactive content. Collagen membranes are widely used in guided tissue regeneration. However, it remains unclear whether combining A-PRF with a collagen membrane alters early cellular responses. This in vitro study compared the effects of A-PRF alone and A-PRF combined with a collagen membrane on the viability, proliferation-related metabolic activity, and migration-related wound closure of human periodontal ligament stem cells (hPDLSCs) at two extract concentrations. Methods: hPDLSCs were exposed to extracts prepared from A-PRF alone or A-PRF combined with a porcine collagen membrane (A-PRF-Col) at 100% and 20% concentrations. Extracts were prepared using A-PRF derived from the blood of four donors. Cell viability was assessed after 24 h using an MTT assay and morphological observation. Proliferation-related metabolic activity was evaluated by MTT assay on days 1, 3, 5, and 7. Migration-related wound closure was evaluated using a scratch assay after 24 h. Data were analysed using repeated-measures ANOVA with post hoc multiple-comparison tests. p < 0.05 was considered statistically significant. Results: Early hPDLSC responses differed between A-PRF and A-PRF-Col and varied between the two extract concentrations. Based on mean relative growth rate values, only 100% A-PRF-Col met the predefined cytotoxicity criterion, whereas 100% A-PRF showed a borderline and donor-variable viability profile. Proliferation-related metabolic activity increased and peaked around day 5, but different concentrations and formulations affected the patterns. Migration-related wound closure was primarily influenced by extract concentration, with 20% extracts showing greater closure than their 100% counterparts. At 20% concentration, A-PRF achieved better closure than A-PRF-Col. Conclusions: Under the present cell-source and extract-preparation conditions, hPDLSC responses differed between A-PRF and A-PRF-Col and varied between the two tested extract concentrations. Diluted extracts generally elicited more favourable early cellular responses than undiluted extracts. The A-PRF-Col construct did not uniformly enhance A-PRF effects across endpoints. These findings should be interpreted as exploratory evidence that A-PRF-Col has an endpoint- and concentration-related biological profile that requires further optimisation. Trial registration: Not applicable.

Background/Objectives: Glass-hybrid and high-viscosity glass-ionomer systems aim to improve conventional glass-ionomer performance. This in vitro study compared Vickers hardness and microleakage of a coated glass-hybrid system and a coated high-viscosity glass-ionomer system in thermocycled conservative Class II cavities in human maxillary first premolars. Methods: Thirty extracted maxillary first premolars were used in a paired within-tooth design. Two standardized conservative Class II cavities, one mesial and one distal, were prepared in each tooth, and each tooth received both systems: EQUIA Forte HT Fil with EQUIA Forte Coat and GC Gold Label IX EXTRA CAPSULE with GC G-Coat Plus. After restoration and thermocycling, Vickers hardness was measured on restoration cross-sections at occlusal and gingival locations. Microleakage was assessed on sectioned specimens using dye penetration measurements and ordinal infiltration scores. Results: EQUIA Forte HT showed a higher tooth-level mean Vickers hardness than Gold Label IX Extra after thermocycling (95.05 ± 6.58 HV vs. 91.33 ± 7.50 HV), with a mean paired difference of 3.72 HV (95% CI: 0.32 to 7.11; p = 0.033). In the location-dependent analysis, the effect of the restorative system was significant (p = 0.025), whereas testing location and the interaction were not significant. The microleakage index and the distributions of occlusal-wall and gingival-wall ordinal infiltration scores did not differ significantly between the two restorative systems. Conclusions: Under the conditions of this in vitro study, EQUIA Forte HT showed a slight tooth-level hardness advantage over Gold Label IX Extra after thermocycling. Neither system showed a statistically significant advantage in dye-based marginal sealing.

Background/Objectives: Glass-hybrid and high-viscosity glass ionomer systems were developed to address limitations of conventional glass ionomer cements. This in vitro study compared post-thermocycling Vickers hardness and microleakage of a coated glass-hybrid system and a coated high-viscosity glass ionomer system in conservative Class II cavities. Methods: Thirty extracted human maxillary first premolars each received both systems in standardized mesio-occlusal and disto-occlusal cavities, enabling paired within-tooth comparisons. Following thermocycling and methylene blue immersion, Vickers hardness was measured on polished restoration cross-sections at occlusal and gingival locations. Microleakage was quantified using a continuous microleakage index and ordinal dye penetration scores. Results: The EQUIA Forte HT system had a higher tooth-level mean Vickers hardness than the Gold Label IX Extra system (95.05 ± 6.58 HV vs. 91.33 ± 7.50 HV), with a mean paired difference of 3.72 HV (95% CI, 0.32 to 7.11; p = 0.033; Cohen’s d_z = 0.41, 95% CI, 0.03 to 0.78). The location-specific mixed model also showed an effect of restorative system (p = 0.025), whereas neither testing location nor the system × location interaction was significant. No significant between-system difference was detected for the microleakage index or for either ordinal dye penetration score. Conclusions: Within the limitations of this in vitro study, the EQUIA Forte HT system had a modestly higher post-thermocycling tooth-level mean Vickers hardness than the Gold Label IX Extra system, although the clinical relevance of the difference remains uncertain. No between-system differences were detected in dye penetration outcomes.