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

Cheah CW, Vaithilingam RD, Siar CH, Swaminathan D, Hornbuckle GC

Implant Dent, 2014 Oct;23(5):593-601.
PMID: 25192162 DOI: 10.1097/ID.0000000000000148

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.
Potential mechanisms linking periodontitis to rheumatoid arthritis

Lee YH, Lew PH, Cheah CW, Rahman MT, Baharuddin NA, Vaithilingam RD

J Int Acad Periodontol, 2019 07 01;21(3):99-110.
PMID: 31473702

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

Sultan T, Cheah CW, Ibrahim NB, Asif MK, Vaithilingam RD

J Dent, 2020 Oct;101:103455.
PMID: 32828845 DOI: 10.1016/j.jdent.2020.103455

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 ± 0.45 mm, p = 0.09) and palatal bone height (PBH = 0.39 ± 0.34 mm, p = 0.06) in PRF-X group. PRF-CS group demonstrated mean horizontal shrinkage of 1.27 ± 0.82 mm (p = 0.02), when compared with PRF-X group (1.40 ± 0.85 mm, p = 0.02). Vertical resorption for mesial bone height (MBH = 0.56 ± 0.25 mm, p = 0.008), buccal bone height (BBH = 1.62 ± 0.91 mm, p = 0.01) and palatal bone height (PBH = 1.39 ± 0.87 mm, p = 0.02) in PRF-CS group was more than resorption in PRF-X group (MBH = 0.28 ± 0.14 mm, p = 0.01, BBH = 0.63 ± 0.39 mm, p = 0.02 and PBH = 0.39 ± 0.34 mm, p = 0.06). Volumetric bone resorption was significant within both groups (PRF-CS = 168.33 ± 63.68 mm3, p = 0.004; PRF-X = 102.88 ± 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 ± 0.50 mm, p = 0.03) demonstrated almost 2 times more reduction when compared with PRF-CS group (DSH = 1.00 ± 1.00 mm, 0.08). The reduction of the buccal soft tissue level was pronounced in PRF-CS group (BSH = 2.00 ± 2.00 mm, p = 0.06) when compared with PRF-X group (BSH = 1.00 ± 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).
Fulltext Synthetic Material for Bone, Periodontal, and Dental Tissue Regeneration: Where Are We Now, and Where Are We Heading Next?

Cheah CW, Al-Namnam NM, Lau MN, Lim GS, Raman R, Fairbairn P, et al.

Materials (Basel), 2021 Oct 15;14(20).
PMID: 34683712 DOI: 10.3390/ma14206123

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 β-tricalcium phosphate (β-TCP) ceramics and biphasic calcium phosphates (hydroxyapatite (HA) and β-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 β-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.
Salivary and serum cathelicidin LL-37 levels in subjects with rheumatoid arthritis and chronic periodontitis

Cheah CW, Al-Maleki AR, Vadivelu J, Danaee M, Sockalingam S, Baharuddin NA, et al.

Int J Rheum Dis, 2020 Oct;23(10):1344-1352.
PMID: 32743970 DOI: 10.1111/1756-185X.13919

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.
Connecting the dots: NETosis and the periodontitis-rheumatoid arthritis nexus

Shahbaz M, Al-Maleki AR, Cheah CW, Aziz J, Bartold PM, Vaithilingam RD

Int J Rheum Dis, 2024 Nov;27(11):e15415.
PMID: 39526323 DOI: 10.1111/1756-185X.15415

Periodontitis (PD) is characterized by the host's inflammatory responses to microbial dental biofilm dysbiosis, potentially resulting in tooth loss if left untreated. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease leading to synovial inflammation and destruction of joint cartilage and bone. The suggested association between PD and RA is based on the potential of chronic inflammation present in periodontitis, which could induce alterations in proteins through post-translational modifications, leading to the formation of citrullinated and carbamylated protein antigens. Antibodies directed against these antigens can serve as biomarkers for the underlying immunological processes in RA. Recent studies have also focused on bacterial proteolytic enzymes released from PD-associated bacteria, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, which are also sources of these antibodies. Chronic inflammation in PD causes increased levels of inflammatory cytokines (interferon-α, interleukins-6 and 8, tumor necrosis factor-α) and neutrophil extracellular traps (NETs). The oral microbiota in PD is also associated with the release of NETs (a process known as NETosis). Elevated NET levels are a source of citrullinated and carbamylated proteins which highlights their role in an individual's risk of developing RA (pre-RA individuals) and the progression of chronic RA. This narrative review describes periodontitis and the dysbiotic subgingival microbiota and its role in NETosis as risk factors for inducing early RA and the prospects of identifying pre-RA individuals and seronegative RA patients with these risk factors.
Fulltext A Narrative Review on Means to Promote Oxygenation and Angiogenesis in Oral Wound Healing

Ngeow WC, Tan CC, Goh YC, Deliberador TM, Cheah CW

Bioengineering (Basel), 2022 Nov 02;9(11).
PMID: 36354548 DOI: 10.3390/bioengineering9110636

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.