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Background: Conflicting results were found regarding the effect of corticosteroid (CS) administration upon wound healing. The objective of this pilot study was to evaluate the impact of CS administration at different time points on palatal wound healing in rats. Methods: A 4.2 mm diameter punch created a secondary healing excisional palatal defect in thirty-six (36) Wistar-derived, two-month-old male rats weighing 250–270 g. We evaluated the effect of CS by comparing wound healing between three equal groups: 12 rats who were not exposed to CS and two additional groups in which 1 mg/kg dexamethasone (1 mg/kg) was administered daily, early (1–4 days) and late (5–9 days) after injury. The dynamics of the healing process were evaluated weekly in 4 sacrificed rats from each group for three weeks. The wound area was assessed both macroscopically and microscopically; the inflammation score was assessed microscopically. Results: The initial wound area in all the rats was 13.85 mm2. At the end of the study, it decreased to 4.11 ± 0.88 mm2, 7.32 ± 2.11 mm2, and 8.87 ± 3.01 mm2 in control, early, and late CS administration groups, respectively (p = 0.075). Inflammation scores showed a tendency to decrease in the third week in all groups, with no statistical differences. Conclusions: Our findings do not support the positive impact of CS administration on palatal wound healing. While microscopically, we found no difference between the CS and control groups, CS exposure was associated with a macroscopically larger final wound area, reflecting a possible harmful effect of CS.

This randomized clinical trial (RCT) compares the effectiveness of ozone gel (GeliO3) and hyaluronic acid (HA) gel (Gengigel) in enhancing wound healing and reducing postoperative discomfort following free gingival graft (FGG) harvesting. Fifty-six patients requiring FGG for mucogingival defects were randomly assigned into two groups: the ozone gel group and the HA gel group. The primary outcome was postoperative pain, assessed using the visual analog scale (VAS) and analgesic consumption. Secondary outcomes included wound healing, evaluated using the Landry healing index, and color match assessment. Data were analyzed using appropriate statistical tests with a significance level of < 0.05. Both treatment groups exhibited significant pain reduction over time ( < 0.001). Although there was no statistically significant difference between the groups, a faster decline in pain was observed in the ozone group by Day 3. Analgesic consumption was significantly lower in the ozone group on Days 2 and 3 ( = 0.042). The healing index and color match scores showed a steady improvement in both groups, with the ozone group demonstrating slightly higher values at various time points, though not statistically significant. Both ozone gel and HA gel effectively enhanced post-FGG healing, reduced pain, and improved tissue esthetics. Ozone therapy showed potential advantages in early pain relief and lower analgesic dependence. These findings suggest that ozone therapy may serve as an alternative or adjunctive treatment for palatal wound management in periodontal surgery. Further research is needed to confirm its clinical superiority over HA gel.

Background and Objectives: Dental implants are recognized as an effective treatment in the management of edentulous patients; controversies surround the connection between the sufficiency of keratinized gingiva (KG) and peri-implant health. Maintaining an ample amount of peri-implant KG is crucial for minimizing gingival inflammation, highlighting the need for regular consideration of soft-tissue augmentation. Among the diverse periodontal plastic surgical procedures, the apically positioned flap (APF) is notable for its ability to enhance the width of keratinized tissue while minimizing patient morbidity. The aim of this study was to evaluate the effects of L-PRF on palatal wound healing and patient discomfort after surgery. Materials and Methods: Twenty patients with two adjacent submerged fixtures in the maxilla and buccal keratinized gingiva widths < 2 mm were treated with APF and L-PRF. Clinical evaluations were performed at 1, 2, 3, and 4 weeks post-surgery, focusing on parameters such as complete wound epithelialization (CWE), postoperative discomfort (D), changes in feeding habits (CFH), alteration of sensitivity (AS) around the wound area, and the consumption of analgesics. Results: Our data revealed CWE in 5 patients by the end of the second week, with the remaining 15 achieving CWE by the end of the third week. For D and CHF, a statistically significant improvement was recorded for all cases between the first and second weeks, as well as AS, although less substantial, by the third week. No significant changes were noted for AS over the initial two weeks. Conclusions: These findings suggest that L-PRF may enhance wound healing and decrease patient discomfort following APF for fixture uncovering.

The accidental injury or surgery on soft and hard palatal tissue has an adverse impact on normal maxillary morphology. To design a single-factor experiment that excludes other interfering factors on maxillary growth, a young rat model was established to simulate the various degrees of palatal trauma. Eight maxillary parameters were measured to evaluate the impact of palatal trauma on maxillary growth. Furthermore, the acellular dermal matrix (ADM) was applied to cure the palatal trauma and alleviate the adverse impact of bone denudation on the maxillary growth. Micro-CT scanning and histology analyses were used. One-way ANOVA with least significant difference (LSD) post-test was used to evaluate the statistical significance. The palatal trauma mainly disturbed the transverse development of the maxilla. ADM promotes mucosa healing, but there is still an inhibitory effect on maxillofacial growth.

Palatal wounds arising from trauma, tumors, cleft palate, or free gingival grafting (FGG) and other etiologies compromise critical orofacial functions including mastication, deglutition phonation and articulation, while posing life-threatening risks in severe conditions. Although surgical resection remains the primary clinical intervention, current treatment strategies for palatal injuries are constrained by several limitations, including: bacterial contamination and chronic inflammation, extensive soft tissue defects, postoperative scar formation, compromised blood supply in the surgical field, and potential patient comorbidities. Research on wound healing based on biomaterials has advanced substantially in recent decades, significantly facilitating their application in tissue engineering. This review provides a comprehensive overview of biomaterials used in palatal wounds, including acellular dermal matrix (ADM), platelet-rich derivatives (e.g., PRF, PRP), amniotic membrane, growth factor, hyaluronic acid, collagen, novel hydrogel, nanofiber scaffolds and other relevant materials. It further discusses potential mechanisms that may be involved in palatal wound healing. The objectives of this review are to summarize recent advances in preclinical and clinical studies on biomaterials for palatal wound healing and to highlight their therapeutic potential in this context.

High mobility group box 1 (HMGB1) is tightly connected to the process of tissue organization upon tissue injury. Here we show that HMGB1 controls epithelium and connective tissue regeneration both in vivo and in vitro during palatal wound healing. Heterozygous HMGB1 (Hmgb1+/−) mice and Wild-type (WT) mice were subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA), anti-nuclear factor-κB (NF-κB) p50 and anti-vascular endothelial growth factor (VEGF) antibodies. Palatal gingival explants were cultured with recombinant HMGB1 (rHMGB1) co-treated with siRNA targeting receptor for advanced glycation end products (RAGEs) for cell migration and PCNA expression analysis. Measurement of the wound area showed differences between Hmgb1+/− and WT mice on Day 3 after wounding. Mallory Azan staining showed densely packed of collagen fibers in WT mice, whereas in Hmgb1+/− mice weave-like pattern of low density collagen bundles were present. At three and seven days post-surgery, PCNA, NF-κB p50 and VEGF positive keratinocytes of WT mice were greater than that of Hmgb1+/− mice. Knockdown of RAGE prevents the effect of rHMGB1-induced cell migration and PCNA expression in gingival cell cultures. The data suggest that HMGB1/RAGE axis has crucial roles in palatal wound healing.

The objective of the present study was to investigate the effect of thymosin β4 (Tβ4) on the wound healing of rat palatal (RP) mucosa and related cellular properties. Cell viability, adhesion and migration of primary cultured RP cells were observed in the presence of Tβ4 at various concentrations ranging from 1 to 1,000 ng/ml. The mRNA and protein expression of matrix metalloproteinase 2 (MMP2) and vascular endothelial growth factor (VEGF) in Tβ4-treated RP cells was assessed by quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. For the in vivo assay, Tβ4 was applied to excisional wounds (3 mm in diameter) that were made in the center of the palate (n=6). Images of the wound areas were captured and assessed histologically one week after surgery. Tβ4 did not affect cell viability and adhesion, but RP cell migration was stimulated by Tβ4 at concentrations of 100 and 1,000 ng/ml. Tβ4 also increased the mRNA and protein expression of MMP2 and VEGF in RP cells. In the animal model, palatal wound closure was significantly enhanced in rats treated with Tβ4. The results of the present study indicated that Tβ4 promotes the wound healing of RP mucosa. Enhancement of RP cell migration and angiogenesis is likely to be involved in the promotion of wound healing.

Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that transforming growth factor (TGF)-β/Smad3 signaling is involved in wound healing. The purpose of this study was to investigate the role of TGF-β/Smad3 signaling in palatal wound healing in Smad3-deficient (Smad3−/−) mice. Histological examination showed that wound closure was accelerated by the proliferation of epithelium and dermal cells in Smad3−/− mice compared with wild-type (WT) mice. Macrophage/monocyte infiltration at wounded regions in Smad3−/− mice was decreased in parallel with the diminished production of TGF-β1, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α compared with WT mice. Fibrocytes, expressing hematopoietic surface marker and fibroblast products, were recruited and produced α-smooth-muscle actin in WT mice, but were not observed in Smad3−/− mice. These results suggest that TGF-β/Smad3 signaling may play an important role in the regulation of palatal wound healing.

Objectives To evaluate the efficacy of topically applied hyaluronic acid on wound healing (patient-reported outcomes and clinical healing) after a palatal autogenous gingival graft is harvested. Materials and methods A systematic search was performed in April 2024 in eleven electronic databases. Two investigators independently screened the references for inclusion. Outcomes of interest included postoperative pain, analgesic consumption, complete epithelialization, and color match, which were synthesized using narrative synthesis. Results A total of 535 results were identified and eight articles were included in the systematic review. Hyaluronic acid use on the palatal donor site had a better response to healing and wound size compared to the control sites with no agent applied. Hyaluronic acid demonstrated a positive effect in the form of complete epithelialization, and color match, with improved patient-reported outcomes such as post-operative pain. Conclusion Within the limitations of this systematic review, it can be concluded that hyaluronic acid shows a strong potential to improve patient-reported outcomes and clinical wound healing at the graft donor site on the palate. Future studies are required to clarify the optimal concentration, frequency of application, and synergistic effect when HA is combined with other interventions. Clinical relevance Within the limitations of this systematic review, it can be concluded that hyaluronic acid shows a strong potential to improve patient-reported outcomes and clinical wound healing at the graft donor site on the palate. Future studies are required to clarify the optimal concentration, frequency of application, and synergistic effect when HA is combined with other interventions.

Dry socket, also known as alveolar osteitis, presents significant challenges in oral surgery because of severe pain and delayed wound healing. This study aims to address these challenges by developing and evaluating a lidocaine-loaded polyelectrolyte complex thermoresponsive gel (LG) designed to enhance wound healing and provide effective pain management in oral wounds. The thermoresponsive gel transitions from a liquid to a gel at body temperature, ensuring sustained contact with the wound site and prolonged release of lidocaine. The in vitro assessments, including cytotoxicity and wound scratch assays, demonstrated the biocompatibility and therapeutic potential of the LG formulation. Following this, palatal wounds were induced in rats, with healing monitored over a 14-days period. Histological analyses were conducted to assess tissue regeneration and inflammation. The results indicated that the LG formulation significantly improved wound closure rates, reduced inflammation, and accelerated epithelialization compared with control groups, primarily because of the high content of hyaluronic acid (HA). The synergistic effects of HA combined with the thermoresponsive properties of the gel facilitated faster healing. These findings suggest that LG is a promising therapeutic option for enhancing oral wound healing and effectively managing pain, particularly in conditions such as dry socket.