Hyaluronic acid in its various forms shows bacteriostatic, fungistatic, anti-inflammatory, anti-edematous, osteoinductive, and pro-angiogenetic properties. This study aimed to evaluate the effect of subgingival delivery of 0.8% hyaluronic acid (HA) gel on clinical periodontal parameters, pro-inflammatory cytokines (IL-1 beta and TNF-alpha) and biochemical markers of inflammation (C-reactive protein (CRP) and alkaline phosphatase (ALP) enzymes) in patients with periodontitis. Seventy-five patients with chronic periodontitis were divided randomly into three groups (25 in each group): group I received scaling and surface root debridement (SRD) + HA gel; group II received SRD + chlorhexidine gel; and group III received surface root debridement alone. Clinical periodontal parameter measurements and blood samples were collected to estimate pro-inflammatory and biochemical parameters at the baseline before therapy and after two months of therapy. The results show that HA gel has a significant effect on the reduction in clinical periodontal parameters (PI, GI, BOP, PPD, and CAL), IL-1 beta, TNF-alpha, CRP, and ALP after 2 months of therapy as compared to the baseline (p < 0.05) with nonsignificant differences from the CHX group (p > 0.05), except GI (p < 0.05), and significant differences from the SRD group (p < 0.05). Moreover, significant differences were found between the three groups regarding the mean improvements of GI, BOP, PPD, IL-1β, CRP, and ALP. It can be concluded that HA gel has a positive effect on clinical periodontal parameters and improvements in inflammatory mediators similar to chlorhexidine. Therefore, HA gel can be used as an adjuvant to SRD in the treatment of periodontitis.

Critical-sized bone defects represent a major clinical challenge, as bone gaps of this magnitude are unable to heal spontaneously without regenerative intervention. The present study aimed to evaluate the dose-dependent osteoinductive effect of rhBMP-2–loaded β-TCP scaffolds on bone regeneration in critical-sized calvarial defects in a rabbit model. Eighteen adult male New Zealand White rabbits were used, and four circular defects (5 mm in diameter) were surgically created in the calvaria of each animal, resulting in a total of 72 defects. The animals were divided into four groups: control, β-TCP + 5 μg rhBMP-2, β-TCP + 10 μg rhBMP-2, and β-TCP + 20 μg rhBMP-2. Bone healing was evaluated at 2, 4, and 8 weeks postoperatively using histological and histomorphometric analyses. Masson’s trichrome staining was performed to assess collagen deposition and maturation, while CD31 immunohistochemical staining was used to evaluate vascularization. The results demonstrated rhBMP-2–loaded β-TCP scaffolds significantly enhanced bone regeneration in a dose-dependent manner, with the β-TCP + 20 μg rhBMP-2 group demonstrating the greatest new bone formation and more mature bone architecture. In addition, BMP-2 treatment promoted osteoblastic activity, improved collagen maturation, and increased vascularization within the defect area. These findings indicate that rhBMP-2–loaded β-TCP scaffolds enhance bone regeneration in a dose-dependent manner, with higher rhBMP-2 doses resulting in greater bone formation and more mature bone architecture.

Nano-engineering strategies have been increasingly applied to enhance the biological performance of calcium silicate-based materials; however, the optimal concentration of nano-hydroxyapatite (HANP) remains unclear. This study evaluated the bone-healing response to different concentrations of HANP incorporated into mineral trioxide aggregate (MTA) and bioceramic (BC) sealers in an experimental rabbit model. Thirty adult New Zealand white rabbits were allocated into two experimental groups according to sealer type: HANP-modified MTA and HANP-modified BC (n = 15 each). Two standardized circular intrabony defects were created bilaterally in the maxillary diastema of each rabbit. In the MTA group, the right-side defects were filled with 2% and 4% HANP-modified MTA, while the left-side defect received 6% HANP-modified MTA, and the adjacent defect was left untreated as a control. The same protocol was followed for the BC group using corresponding HANP concentrations. Five rabbits per group were sacrificed at 2, 4, and 8 weeks postoperatively for histopathological hematoxylin and eosin (H&E) and Masson trichrome staining. The results demonstrated significant differences among groups at all time points, with 4% HANP showing the most favorable biological response, including reduced inflammatory cell infiltration, increased new bone formation, and improved collagen organization compared with lower and higher concentrations. Pairwise comparisons at matched HANP concentrations revealed no statistically significant differences between HANP-modified MTA and BC groups. These findings indicate that HANP incorporation enhances the biological performance of calcium silicate-based sealers in a concentration-dependent manner, with 4% representing the most favorable response among the concentrations evaluated for promoting bone regeneration.

Critical-sized bone defects represent a major clinical challenge, as defects of this magnitude do not heal spontaneously without regenerative intervention. This study aimed to evaluate the osteoinductive effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded β-tricalcium phosphate (β-TCP) scaffolds on bone regeneration and vascularization in a rabbit calvarial critical-sized defect model. Eighteen male New Zealand White rabbits were used, and four standardized circular defects (5 mm in diameter) were created in the calvaria of each animal. The defects were assigned to four groups: control (unfilled), β-TCP + 5 µg rhBMP-2, β-TCP + 10 µg rhBMP-2, and β-TCP + 20 µg rhBMP-2. Bone healing was evaluated at 2, 4, and 8 weeks using histological, histomorphometric, and cluster of differentiation 31 (CD31) immunohistochemical analyses. The results demonstrated that rhBMP-2–loaded β-TCP scaffolds significantly enhanced bone regeneration compared with the control group, with a progressive increase in bone formation observed with increasing rhBMP-2 doses. The β-TCP + 20 µg rhBMP-2 group exhibited the highest levels of new bone formation, more advanced bone maturation, improved collagen organization, and increased vascularization. However, no statistically significant differences were observed between the 10 µg and 20 µg groups at later time points (p > 0.05), suggesting a dose-dependent saturation (plateau) effect. In conclusion, rhBMP-2–loaded β-TCP scaffolds promote bone regeneration and angiogenesis in a dose-related manner up to a threshold, beyond which additional increases in dose do not result in proportional improvements. These findings emphasize that optimal rhBMP-2 dosing is critical to maximize regenerative outcomes while avoiding unnecessary dose escalation.

Nano-engineering strategies have been increasingly applied to enhance the biological performance of calcium silicate–based materials; however, the optimal concentration of nano-hydroxyapatite (HANP) remains unclear. This study evaluated the bone-healing response to different concentrations of HANP incorporated into mineral trioxide aggregate (MTA) and bioceramic (BC) sealers in an experimental rabbit model. Thirty adult New Zealand white rabbits were allocated into two experimental groups according to sealer type: HANP-modified MTA and HANP-modified BC (n = 15 each). Two standardized circular intrabony defects were created bilaterally in the maxillary diastema of each rabbit. In the MTA group, the right-side defects were filled with 2% and 4% HANP-modified MTA, while on the left side one defect received 6% HANP-modified MTA and the adjacent defect was left as control. The same protocol was followed for the BC group using corresponding HANP concentrations. Five rabbits per group were sacrificed at 2, 4, and 8 weeks postoperatively for histopathological hematoxylin and eosin (H&E) and Masson trichrome staining. The results demonstrated significant differences among groups at all-time points, with 4% HANP showing the most favorable biological response, including reduced inflammatory cell infiltration, increased new bone formation, and improved collagen organization compared with lower and higher concentrations. Pairwise comparisons at matched HANP concentrations revealed no statistically significant differences between HANP-modified MTA and BC groups. These findings indicate that HANP incorporation enhances the biological performance of calcium silicate–based sealers in a concentration-dependent manner, with 4% representing an optimal formulation for promoting bone regeneration.