A Narrative Review on Means to Promote Oxygenation and Angiogenesis in Oral Wound Healing.

Oral mucosa serves as the primary barrier against pathogen invasions, mechanical stresses, and physical trauma. Although it is generally composed of keratinocytes and held in place by desmosomes, it shows variation in tissue elasticity and surface keratinization at different sites of the oral cavity. Wound healing undergoes four stages of tissue change sequences, namely haemostasis, inflammation, proliferation, and remodelling. The wound healing of oral hard tissue and soft tissue is largely dependent on the inflammatory response and vascular response, which are the targets of many research. Because of a less-robust inflammatory response, favourable saliva properties, a unique oral environment, and the presence of mesenchymal stem cells, oral wounds are reported to demonstrate rapid healing, less scar formation, and fewer inflammatory reactions. However, delayed oral wound healing is a major concern in certain populations with autoimmune disorders or underlying medical issues, or those subjected to surgically inflicted injuries. Various means of approach have been adopted to improve wound tissue proliferation without causing excessive scarring. This narrative review reappraises the current literature on the use of light, sound, mechanical, biological, and chemical means to enhance oxygen delivery to wounds. The current literature includes the use of hyperbaric oxygen and topical oxygen therapy, ultrasounds, lasers, platelet-rich plasma (PRP)/platelet-rich fibrin (PRF), and various chemical agents such as hyaluronic acid, astaxanthin, and Centella asiatica to promote angiogenesis in oral wound healing during the proliferation process. The arrival of a proprietary oral gel that is reported to improve oxygenation is highlighted.

Associations between inflammation-related LL-37 with subgingival microbial dysbiosis in rheumatoid arthritis patients.

OBJECTIVE: This study investigated the subgingival microbial profile of rheumatoid arthritis (RA) patients and its associations with disease parameters and the inflammation-related antimicrobial peptide, LL-37. METHODS: RA and non-RA (NRA) patients were assessed for periodontal status and divided into periodontitis (CP), gingivitis (G), and healthy (H) groups. Subgingival plaque 16s rRNA gene sequencing data was processed and analyzed using the CLC Genomic Workbench (Qiagen). Bacterial diversity and co-occurrence patterns were examined. Differential abundance between groups was also investigated. Associations between bacterial genera with disease parameters and LL-37 levels were explored qualitatively using canonical correlation analysis. RESULTS: Subgingival microbial community clustered in CP status. Co-occurrence network in NRA-H was dominated by health-associated genera, while the rest of the networks' key genera were both health- and disease-associated. RA-CP displayed highly inter-generic networks with a statistically significant increase in periodontal disease-associated genera (p<0.05). In NRA-H, disease parameters and LL-37 were correlated positively with disease-associated genera while negatively with health-associated genera. However, in the remaining groups, mixed positive and negative correlations were noted with genera. CONCLUSION: RA patients demonstrated subgingival microbial dysbiosis where the bacteria networks were dominated by health- and disease-associated genera. Mixed correlations with disease parameters and LL-37 levels were noted. CLINICAL RELEVANCE: The subgingival microbial dysbiosis in RA may predispose these patients to developing periodontal inflammation with an associated detrimental effect on host immune responses. Routine periodontal assessment may allow initiation of treatment strategies to minimize the effects of gingival inflammation on the existing heightened immune response present in RA patients.

Synthetic Material for Bone, Periodontal, and Dental Tissue Regeneration: Where Are We Now, and Where Are We Heading Next?

Alloplasts are synthetic, inorganic, biocompatible bone substitutes that function as defect fillers to repair skeletal defects. The acceptance of these substitutes by host tissues is determined by the pore diameter and the porosity and inter-connectivity. This narrative review appraises recent developments, characterization, and biological performance of different synthetic materials for bone, periodontal, and dental tissue regeneration. They include calcium phosphate cements and their variants ß-tricalcium phosphate (ß-TCP) ceramics and biphasic calcium phosphates (hydroxyapatite (HA) and ß-TCP ceramics), calcium sulfate, bioactive glasses and polymer-based bone substitutes which include variants of polycaprolactone. In summary, the search for synthetic bone substitutes remains elusive with calcium compounds providing the best synthetic substitute. The combination of calcium sulphate and ß-TCP provides improved handling of the materials, dispensing with the need for a traditional membrane in guided bone regeneration. Evidence is supportive of improved angiogenesis at the recipient sites. One such product, (EthOss® Regeneration, Silesden, UK) has won numerous awards internationally as a commercial success. Bioglasses and polymers, which have been used as medical devices, are still in the experimental stage for dental application. Polycaprolactone-TCP, one of the products in this category is currently undergoing further randomized clinical trials as a 3D socket preservation filler. These aforementioned products may have vast potential for substituting human/animal-based bone grafts.

Three-dimensional assessment of the extraction sockets, augmented with platelet-rich fibrin and calcium sulfate: A clinical pilot study.

OBJECTIVES: This clinical study assessed and compared the linear and volumetric changes of extraction sockets grafted with a combination of Platelet-Rich Fibrin (PRF) and Calcium Sulfate (CS) (PRF-CS), and extraction sockets grafted with a combination of PRF and xenograft (X) (PRF-X). METHODS: Five single maxillary premolar extraction sockets received PRF-CS grafts and five single maxillary premolar sockets received PRF-X grafts. Linear (horizontal and vertical) measurements were accomplished using Cone Beam Computed Tomography (CBCT) images and volumetric changes were assessed using MIMICS software. Soft tissue level changes were measured using Stonecast models. All measurements were recorded at baseline (before extraction) and at 5-months post-extraction. RESULTS: Significant reduction in vertical and horizontal dimensions were observed in both groups except for distal bone height (DBH = 0.44 ±â€¯0.45 mm, p = 0.09) and palatal bone height (PBH = 0.39 ±â€¯0.34 mm, p = 0.06) in PRF-X group. PRF-CS group demonstrated mean horizontal shrinkage of 1.27 ±â€¯0.82 mm (p = 0.02), when compared with PRF-X group (1.40 ±â€¯0.85 mm, p = 0.02). Vertical resorption for mesial bone height (MBH = 0.56 ±â€¯0.25 mm, p = 0.008), buccal bone height (BBH = 1.62 ±â€¯0.91 mm, p = 0.01) and palatal bone height (PBH = 1.39 ±â€¯0.87 mm, p = 0.02) in PRF-CS group was more than resorption in PRF-X group (MBH = 0.28 ±â€¯0.14 mm, p = 0.01, BBH = 0.63 ±â€¯0.39 mm, p = 0.02 and PBH = 0.39 ±â€¯0.34 mm, p = 0.06). Volumetric bone resorption was significant within both groups (PRF-CS = 168.33 ±â€¯63.68 mm3, p = 0.004; PRF-X = 102.88 ±â€¯32.93 mm3, p = 0.002), though not significant (p = 0.08) when compared between groups. In PRF-X group, the distal soft tissue level (DSH = 1.00 ±â€¯0.50 mm, p = 0.03) demonstrated almost 2 times more reduction when compared with PRF-CS group (DSH = 1.00 ±â€¯1.00 mm, 0.08). The reduction of the buccal soft tissue level was pronounced in PRF-CS group (BSH = 2.00 ±â€¯2.00 mm, p = 0.06) when compared with PRF-X group (BSH = 1.00 ±â€¯1.50 mm, p = 0.05). CONCLUSIONS: PRF-CS grafted sites showed no significant difference with PRF-X grafted sites in linear and volumetric dimensional changes and might show clinical benefits for socket augmentation. The study is officially registered with ClinicalTrials.gov Registration (NCT03851289).

Salivary and serum cathelicidin LL-37 levels in subjects with rheumatoid arthritis and chronic periodontitis.

INTRODUCTION: Rheumatoid arthritis (RA) is associated with chronic periodontitis (CP) due to shared risk factors, immuno-genetics and tissue destruction pathways. Human cathelicidin LL-37 has been suggested as a possible mechanistic link for these diseases. This study investigated the levels of salivary and serum LL-37 in subjects with RA and CP and their correlation with disease parameters. METHOD: Subjects were allocated into RA (n = 49) or non-RA (NRA) (n = 55) groups, where 3 subgroups were further established; chronic periodontitis (CP), gingivitis (G) and periodontal health (H). Demographic and periodontal parameters were collected. Rheumatology data were obtained from hospital records. Serum and salivary LL-37 levels were measured using enzyme-linked immunosorbent assay and compared for all groups. RESULTS: For salivary LL-37, RA-CP was significantly higher than NRA-G and NRA-H (P = .047). For serum LL-37, all RA and NRA-CP were significantly higher than NRA-G and NRA-H (P = .024). Salivary LL-37 correlated negatively with clinical attachment loss (CAL) (P = .048), but positively with erythrocyte sedimentation rate (ESR) in RA-H (P = .045). Serum LL-37 showed positive correlation with ESR (P = .037) in RA-G, with C-reactive protein (P = .017) in RA-H, but negative correlation with number of teeth (P = .002) in NRA-CP. Rheumatology data correlated positively with periodontal parameters in RA-CP group. CONCLUSION: NRA-CP subjects with high serum LL-37 should receive comprehensive periodontal therapy. Positive correlation between rheumatology data and periodontal parameters showed that RA disease stability may be obtained by assessing the periodontal condition. Periodontal therapy is necessary to compliment RA treatment to achieve optimum outcome for RA patients with concurrent CP.

Clinical Evaluation of Obesity In Patients with Type 2 Diabetes Mellitus after Periodontal Treatment: A Comparative Study.

AIM: Periodontitis is often associated with diabetes mellitus and may be considered one of the chronic complications of this disease. Increasing evidence indicates that periodontal disease (gingivitis and periodontitis) has an adverse effect on glycemic control and participates in the pathophysiology of complications related to type 2 diabetes mellitus. Thus, this study aimed to evaluate the influence of obesity on clinical periodontal parameters of patients with type 2 diabetes mellitus with stage II or III periodontitis grade C after conventional periodontal treatment. METHODS: For this study, 36 patients, aged 25 to 65 years, were evaluated; 20 patients with type 2 diabetes mellitus and moderate to severe periodontitis (Non-Obese Group) and 16 patients with type 2 diabetes mellitus with obesity and moderate to severe periodontitis (Obese Group). These patients underwent conventional periodontal treatment and were evaluated using plaque index, probing depth, clinical attachment level, bleeding on probing and gingival crevicular fluid analysis, as well as laboratory tests of glycated hemoglobin, fasting glycemia, total cholesterol, and fractions of triglycerides. Periodontal and laboratory parameters were evaluated at baselineand six months. RESULTS: The results showed improvements in periodontal and clinical laboratory parameters(p less than 0.05) in the evaluated periods; however, the non-obese group presented significantly better results when compared to the obese group. CONCLUSION: It can be concluded that the presence of obesity may hinder the improvement of periodontal clinical parameters after conventional periodontal treatment in patients with diabetes mellitus and periodontitis.

Potential mechanisms linking periodontitis to rheumatoid arthritis.

Periodontitis (PD), a chronic inflammatory disease which results in irreversible attachment loss, bone destruction and tooth loss, is a major oral health problem. Rheumatoid arthritis (RA), with a global prevalence of 1%, is an autoimmune disease characterized as a chronic inflammatory disorder leading to synovial inflammation and destruction of cartilage and bone. Studies have reported an association between PD and RA whereby PD is reportedly more severe in patients with established RA. Justification for the plausible link between both conditions is based on shared characteristics and pathogenic similarities with regard to risk factors, immunogenetics and tissue destruction pathways. The search for the possible mechanism linking PD to RA continues as it can play an important role in enabling early intervention in the form of prevention and treatment of infection. This will ultimately improve patients' oral health related quality of life and reduce societal burden related to increased patient discomfort and treatment costs. The current review provides an update on the cellular and molecular events that have thus far explained the link.

Histologic, histomorphometric, and cone-beam computerized tomography analyses of calcium sulfate and platelet-rich plasma in socket preservation: a pilot study.

OBJECTIVES: To assess dimensional changes and histologic/histomorphometric aspects of grafted sockets using either calcium sulfate-platelet-rich plasma (CS-PRP) or CS alone in socket preservation procedure. STUDY DESIGN: Twelve subjects with single nonmolar teeth underwent atraumatic extraction. Six sockets received CS grafts and 6 sockets received CS-PRP grafts. Cone-beam computerized tomography scans taken immediately after extraction and 4 months after surgery were used to measure vertical and horizontal dimensional changes. Histologic and histomorphometric analyses of grafted sites were performed at 4 months after surgery. Intergroup changes were compared using Mann-Whitney U test. RESULTS: CS group demonstrated 18.6% horizontal resorption as compared with 9.2% in CS-PRP group. Resorption for buccal height (BH) (14%) and palatal/lingual height (PH) (13.7%) in CS group was nearly 3 times more than resorption in BH (5%) and PH (4.6%) for CS-PRP group. Mineralized bone component in CS-PRP group (11.19% ± 6.59%) was significantly more than CS group (1.51% ± 2.86%) (P = 0.01). CONCLUSION: CS-PRP-grafted sites demonstrated higher mineralized bone content than CS-grafted sites.