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Managing complications of radiation therapy in head and neck cancer patients: Part III. Provision of dentures

Rahman RA, Ngeow WC, Chai WL, Ramli R

Singapore Dent J, 2006 Dec;28(1):7-10.
PMID: 17378335

Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Pretreatment dental assessment should be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally and, as a result, they succumb to complicated oral adverse effects after radiation therapy. The management of radiation-induced caries, a sequelae of xerostomia has been reviewed in Part II of this series. In this article, the management of difficulty with dentures, another sequelae of xerostomia following radiation therapy is reviewed.
Managing complications of radiation therapy in head and neck cancer patients: Part VI. Management of opportunistic infections

Ngeow WC, Chai WL, Ramli R, Rahman RA

Singapore Dent J, 2006 Dec;28(1):19-21.
PMID: 17378338

Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Where possible, pretreatment dental assessment shall be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally for radiation therapy. Because of this, they succumb to complicated oral adverse effects after radiation therapy. The last part of this series reviews the opportunistic infections that can occur to the perioral structure. Their management is briefly discussed.
Managing complications of radiation therapy in head and neck cancer patients: Part V. Management of mucositis

Ngeow WC, Chai WL, Rahman RA, Ramli R

Singapore Dent J, 2006 Dec;28(1):16-8.
PMID: 17378337

Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Where possible, pretreatment dental assessment shall be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally for radiation therapy. Because of this, they succumb to complicated oral adverse effects after radiation therapy. The second last part of this series reviews and discusses the management of complication that commonly occur to the oral mucosa, i.e. mucositis.
Modified silk fibroin scaffolds with collagen/decellularized pulp for bone tissue engineering in cleft palate: Morphological structures and biofunctionalities

Sangkert S, Meesane J, Kamonmattayakul S, Chai WL

Mater Sci Eng C Mater Biol Appl, 2016 Jan 1;58:1138-49.
PMID: 26478414 DOI: 10.1016/j.msec.2015.09.031

Cleft palate is a congenital malformation that generates a maxillofacial bone defect around the mouth area. The creation of performance scaffolds for bone tissue engineering in cleft palate is an issue that was proposed in this research. Because of its good biocompatibility, high stability, and non-toxicity, silk fibroin was selected as the scaffold of choice in this research. Silk fibroin scaffolds were prepared by freeze-drying before immerging in a solution of collagen, decellularized pulp, and collagen/decellularized pulp. Then, the immersed scaffolds were freeze-dried. Structural organization in solution was observed by Atomic Force Microscope (AFM). The molecular organization of the solutions and crystal structure of the scaffolds were characterized by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD), respectively. The weight increase of the modified scaffolds and the pore size were determined. The morphology was observed by a scanning electron microscope (SEM). Mechanical properties were tested. Biofunctionalities were considered by seeding osteoblasts in silk fibroin scaffolds before analysis of the cell proliferation, viability, total protein assay, and histological analysis. The results demonstrated that dendrite structure of the fibrils occurred in those solutions. Molecular organization of the components in solution arranged themselves into an irregular structure. The fibrils were deposited in the pores of the modified silk fibroin scaffolds. The modified scaffolds showed a beta-sheet structure. The morphological structure affected the mechanical properties of the silk fibroin scaffolds with and without modification. Following assessment of the biofunctionalities, the modified silk fibroin scaffolds could induce cell proliferation, viability, and total protein particularly in modified silk fibroin with collagen/decellularized pulp. Furthermore, the histological analysis indicated that the cells could adhere in modified silk fibroin scaffolds. Finally, it can be deduced that modified silk fibroin scaffolds with collagen/decellularized pulp had the performance for bone tissue engineering and a promise for cleft palate treatment.
Fulltext Avoiding Osteoradionecrosis - The Dental Surgeo's Nightmaren

Roszalina R, Chai WL, Ngeow WC, Roslan AR

Med J Malaysia, 2002 Jun;57(2):246-50.
PMID: 24326664

Osteoradionecrosis is a severe debilitating complication; it may occur from radiotherapy to the bones. It is a dental surgeon's nightmare as it may be long standing and difficult to manage. Osteoradionecrosis is characterised by hypoxia, hypocellularity and hypovascularity of the affected tissue. This paper reviews osteoradionecrosis in relation to dental treatment.
Clinicopathologic study of odontogenic keratocysts in Singapore and Malaysia

Ngeow WC, Zain RB, Yeo JF, Chai WL

J Oral Sci, 2000 Mar;42(1):9-14.
PMID: 10808269

This was a retrospective study of odontogenic keratocysts in people from the Singapore-Malaysian region. The purpose of this study was to present the clinicopathologic features of odontogenic keratocysts in the Oriental population and to compare these data with those from other reported studies. Biopsy records from 1981 to 1992 of 61 cases of odontogenic keratocysts from patients in Malaysia and Singapore showed that 42.6% of patients were female and 57.4% of patients were male. Among patients with cysts, 75.4% were Chinese, 6.6% were Malays, 9.8% were Indians and 8.2% were other ethnic groups. The mean age of these patients was 26.98 +/- 15.38 years with a peak incidence occurring in the second to fourth decades. The location of the lesions was more often in the mandible (65.5%) than the maxilla (31.0%). There was a marked predilection for lesions to occur in the posterior mandible. Histologically, 90.2% of the cysts were lined with a para-keratinized stratified squamous epithelium while only 3.3% of the cysts were lined with orthokeratinized stratified squamous epithelium. Mixed para-keratinized and orthokeratinized epithelial linings were observed in 4 cases (6.5%). The cyst linings were mainly uninflamed (95.1%). Inflammation of the cyst wall was found in 42 cases (68.8%). Twelve (19.7%) cases contained keratin in the lumen. A satellite cyst was observed in only 6 cases (9.8%). In conclusion, most clinical and histological features seen in this study were similar to those found for Caucasians. The only clinical feature that was different was the peak age incidence, that ranged from the second to fourth decades, with an absence of a second peak. Odontogenic keratocysts presenting at the site of the dentigerous cyst were observed in 7 cases (11.5%).
Modified porous scaffolds of silk fibroin with mimicked microenvironment based on decellularized pulp/fibronectin for designed performance biomaterials in maxillofacial bone defect

Sangkert S, Kamonmattayakul S, Chai WL, Meesane J

J Biomed Mater Res A, 2017 Jun;105(6):1624-1636.
PMID: 28000362 DOI: 10.1002/jbm.a.35983

Maxillofacial bone defect is a critical problem for many patients. In severe cases, the patients need an operation using a biomaterial replacement. Therefore, to design performance biomaterials is a challenge for materials scientists and maxillofacial surgeons. In this research, porous silk fibroin scaffolds with mimicked microenvironment based on decellularized pulp and fibronectin were created as for bone regeneration. Silk fibroin scaffolds were fabricated by freeze-drying before modification with three different components: decellularized pulp, fibronectin, and decellularized pulp/fibronectin. The morphologies of the modified scaffolds were observed by scanning electron microscopy. Existence of the modifying components in the scaffolds was proved by the increase in weights and from the pore size measurements of the scaffolds. The modified scaffolds were seeded with MG-63 osteoblasts and cultured. Testing of the biofunctionalities included cell viability, cell proliferation, calcium content, alkaline phosphatase activity (ALP), mineralization and histological analysis. The results demonstrated that the modifying components organized themselves into aggregations of a globular structure. They were arranged themselves into clusters of aggregations with a fibril structure in the porous walls of the scaffolds. The results showed that modified scaffolds with a mimicked microenvironment of decellularized pulp/fibronectin were suitable for cell viability since the cells could attach and spread into most of the pores of the scaffold. Furthermore, the scaffolds could induce calcium synthesis, mineralization, and ALP activity. The results indicated that modified silk fibroin scaffolds with a mimicked microenvironment of decellularized pulp/fibronectin hold promise for use in tissue engineering in maxillofacial bone defects. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1624-1636, 2017.
Fulltext Expression of Interleukin-1β and Histological Changes of the Three-Dimensional Oral Mucosal Model in Response to Yttria-Stabilized Nanozirconia

Nasarudin NA, Razali M, Goh V, Chai WL, Muchtar A

Materials (Basel), 2023 Mar 01;16(5).
PMID: 36903142 DOI: 10.3390/ma16052027

Over the years, advancement in ceramic-based dental restorative materials has led to the development of monolithic zirconia with increased translucency. The monolithic zirconia fabricated from nano-sized zirconia powders is shown to be superior in physical properties and more translucent for anterior dental restorations. Most in vitro studies on monolithic zirconia have focused mainly on the effect of surface treatment or the wear of the material, while the nanotoxicity of this material is yet to be explored. Hence, this research aimed to assess the biocompatibility of yttria-stabilized nanozirconia (3-YZP) on the three-dimensional oral mucosal models (3D-OMM). The 3D-OMMs were constructed using human gingival fibroblast (HGF) and immortalized human oral keratinocyte cell line (OKF6/TERT-2), co-cultured on an acellular dermal matrix. On day 12, the tissue models were exposed to 3-YZP (test) and inCoris TZI (IC) (reference material). The growth media were collected at 24 and 48 h of exposure to materials and assessed for IL-1β released. The 3D-OMMs were fixed with 10% formalin for the histopathological assessments. The concentration of the IL-1β was not statistically different between the two materials for 24 and 48 h of exposure (p = 0.892). Histologically, stratification of epithelial cells was formed without evidence of cytotoxic damage and the epithelial thickness measured was the same for all model tissues. The excellent biocompatibility of nanozirconia, as evidenced by the multiple endpoint analyses of the 3D-OMM, may indicate the potential of its clinical application as a restorative material.
Contour analysis of an implant--soft tissue interface

Chai WL, Moharamzadeh K, van Noort R, Emanuelsson L, Palmquist A, Brook IM

J Periodontal Res, 2013 Oct;48(5):663-70.
PMID: 23442017 DOI: 10.1111/jre.12062

Studies of peri-implant soft tissue on in vivo models are commonly based on histological sections prepared using undecalcified or 'fracture' techniques. These techniques require the cutting or removal of implant during the specimen preparation process. The aim of this study is to explore a new impression technique that does not require any cutting or removal of implant for contour analysis of soft tissue around four types of titanium (Ti) surface roughness using an in vitro three-dimensional oral mucosal model (3D OMM).
Contour Analysis of Three-Dimensional Peri-Implant Mucosal Model as an Endpoint Analysis of Photofunctionalization Effects on Implant Abutment Materials

Razali M, Chai WL, Omar RA, Ngeow WC

Materials (Basel), 2023 Aug 09;16(16).
PMID: 37629819 DOI: 10.3390/ma16165529

INTRODUCTION: The objective of this study was to examine the effect of photofunctionalization on the soft-tissue contour formed at the interface of various abutment materials using end-point analyses obtained from the three-dimensional oral mucosal model (3D-OMMs).
METHODS: Commercially pure titanium (CPTi), alumina-toughened zirconia (ATZ), and yttria-stabilized zirconia (YSZ) made into discs shapes were classified into two groups: UV-treated (PTx) and non-treated (NTx). The materials in PTx groups were exposed to UV light for 12 min. Human gingival fibroblasts and TR146 epithelial cell lines co-cultured on the acellular dermal membrane were used to construct the 3D-OMM. After 4 days of culture, the discs were inserted into the holes prepared within the membrane of 3D-OMMs. The contour formed by the tissue was evaluated after 14 days of culture.
RESULTS: The UV treatment of abutment materials resulted in the formation of more non-pocket-tissue types among the PTx group (p = 0.002). Of all materials tested, soft tissue contour around YSZ showed higher scores for the non-pocket type in both non- and UV-treated groups.
CONCLUSIONS: The non-pocket type of tissue attachment was frequently found in all surfaces modified by photofunctionalization, particularly zirconia. The 3D-OMM can be used to evaluate the biological endpoints of implant surface modifications.
Fulltext CRC14: Different Approaches to Morse Taper Abutment Fracture

Lim EL, Ngeow WC, Lim D, Chai WL

J Indian Prosthodont Soc, 2018 Oct;18(Suppl 1):S41.
PMID: 30532466 DOI: 10.4103/0972-4052.244669
The Management of Persistent Pain From a Branch of the Trifid Mandibular Canal due to Implant Impingement

Aljunid S, AlSiweedi S, Nambiar P, Chai WL, Ngeow WC

J Oral Implantol, 2016 Aug;42(4):349-52.
PMID: 27078072 DOI: 10.1563/aaid-joi-D-16-00011

The mandibular canal is a conduit that allows the inferior alveolar neurovascular bundle to transverse the mandible to supply the dentition, jawbone, and soft tissue around the lower lip. It is now acknowledged that the mandibular canal is not a single canal but an anatomical structure with multiple branches and variations. Iatrogenic injury to branches of the mandibular canal that carry a neurovascular bundle has been reported to cause injury to the main canal as severe as if the main canal itself is traumatized. These injuries include bleeding, neurosensory disturbance, or the formation of traumatic neuroma, and so far, they have involved cases with the bifid mandibular canal. This current report presents a case of neurosensory disturbance that resulted from the impingement of a branch of a trifid mandibular canal during implant insertion. Its management included analgesics, reexamination, and reinserting a shorter implant.
Detection of host-specific immunogenic proteins in the saliva of patients with oral squamous cell carcinoma

Mu AK, Chan YS, Kang SS, Azman SN, Zain RB, Chai WL, et al.

J Immunoassay Immunochem, 2014;35(2):183-93.
PMID: 24295181 DOI: 10.1080/15321819.2013.836535

The main purpose of this article is to develop a new and reliable saliva-based clinical diagnostic method for the early detection of oral squamous cell carcinoma (OSCC). This study used an immunoproteomic approach which allowed the detection of immunogenic host proteins in patients' samples using pooled human antibodies. In an attempt to investigate potential biomarkers of OSCC, two-dimensional electrophoresis (2-DE) followed by immunoblotting of saliva from patients and controls were compared. The protein spots of interest were analyzed using 2-DE image analyzer and subsequently subjected to MALDI-TOF/TOF and then matched against NCBI database. The result showed that four protein clusters, namely Human Pancreatic Alpha-amylase (HPA), Human Salivary Amylase (sAA), keratin-10 (K-10), and Ga Module Complexed with Human Serum Albumin (GA-HSA), had exhibited immunoreactivity in western blot. The results are suggestive of the potential use of the differentially expressed saliva protein as tumor biomarkers for the detection of OSCC. However, further studies are recommended to validate this finding.
Fulltext Quantification of the dental morphology of orangutans

Nambiar P, John J, Al-Amery SM, Purmal K, Chai WL, Ngeow WC, et al.

ScientificWorldJournal, 2013;2013:213757.
PMID: 24348143 DOI: 10.1155/2013/213757

Orangutans are believed to have close biological affinities to humans. Teeth being the hardest tissue provide useful information on primate evolution. Furthermore, knowledge of the pulp chamber and root canal morphology is important for dental treatment. A female Bornean orangutan and a Sumatran male orangutan skull were available for this study. Both of their dentitions, comprising 50 teeth, were scanned employing the cone-beam computed tomography for both metrical and nonmetrical analyses. Measurements included tooth and crown length, root length, enamel covered crown height, root canal length (posterior teeth), length of pulpal space (anterior teeth), and root canal width. Nonmetrical parameters included number of canals per root, number of foramina in each root, and root canal morphology according to Vertucci's classification. It was found that the enamel covered crown height was the longest in the upper central incisors although the canine was the longest amongst the anterior teeth. Both the upper premolars were three-rooted while the lower second premolar of the Sumatran orangutan was two-rooted, with two foramina. The mandibular lateral incisors of the Bornean orangutan were longer than the central incisors, a feature similar to humans. In addition, secondary dentine deposition was noticed, a feature consistent with aged humans.
Fulltext The biological seal of the implant-soft tissue interface evaluated in a tissue-engineered oral mucosal model

Chai WL, Brook IM, Palmquist A, van Noort R, Moharamzadeh K

J R Soc Interface, 2012 Dec 7;9(77):3528-38.
PMID: 22915635 DOI: 10.1098/rsif.2012.0507

For dental implants, it is vital that an initial soft tissue seal is achieved as this helps to stabilize and preserve the peri-implant tissues during the restorative stages following placement. The study of the implant-soft tissue interface is usually undertaken in animal models. We have developed an in vitro three-dimensional tissue-engineered oral mucosal model (3D OMM), which lends itself to the study of the implant-soft tissue interface as it has been shown that cells from the three-dimensional OMM attach onto titanium (Ti) surfaces forming a biological seal (BS). This study compares the quality of the BS achieved using the three-dimensional OMM for four types of Ti surfaces: polished, machined, sandblasted and anodized (TiUnite). The BS was evaluated quantitatively by permeability and cell attachment tests. Tritiated water (HTO) was used as the tracing agent for the permeability test. At the end of the permeability test, the Ti discs were removed from the three-dimensional OMM and an Alamar Blue assay was used for the measurement of residual cells attached to the Ti discs. The penetration of the HTO through the BS for the four types of Ti surfaces was not significantly different, and there was no significant difference in the viability of residual cells that attached to the Ti surfaces. The BS of the tissue-engineered oral mucosa around the four types of Ti surface topographies was not significantly different.
Ultrastructural analysis of implant-soft tissue interface on a three dimensional tissue-engineered oral mucosal model

Chai WL, Brook IM, Emanuelsson L, Palmquist A, van Noort R, Moharamzadeh K

J Biomed Mater Res A, 2012 Feb;100(2):269-77.
PMID: 22045611 DOI: 10.1002/jbm.a.33245

A three dimensional tissue-engineered human oral mucosal model (3D OMM) used in the investigation of implant-soft tissue interface was recently reported. The aim of this study was to examine the ultrastructural features of soft tissue attachment to various titanium (Ti) implant surfaces based on the 3D OMM. Two techniques, that is, focus ion beam (FIB) and electropolishing techniques were used to prepare specimens for transmission electron microscopic (TEM) analysis of the interface. The 3D OM consisting of both epithelial and connective tissue layers was constructed by co-culturing human oral keratinocytes and fibroblasts onto an acellular dermis scaffold. Four types of Ti surface topographies were tested: polished, machined (turned), sandblasted, and TiUnite. The specimens were then processed for TEM examination using FIB (Ti remained) and electropolishing (Ti removed) techniques. The FIB sections showed some artifact and lack of details of ultrastructural features. In contrast, the ultrathin sections prepared from the electropolishing technique showed a residual Ti oxide layer, which preserved the details for intact ultrastructural interface analysis. There was evidence of hemidesmosome-like structures at the interface on the four types of Ti surfaces, which suggests that the tissue-engineered oral mucosa formed epithelial attachments on the Ti surfaces.
Development of a novel model for the investigation of implant-soft tissue interface

Chai WL, Moharamzadeh K, Brook IM, Emanuelsson L, Palmquist A, van Noort R

J. Periodontol., 2010 Aug;81(8):1187-95.
PMID: 20450401 DOI: 10.1902/jop.2010.090648

In dental implant treatment, the long-term prognosis is dependent on the biologic seal formed by the soft tissue around the implant. The in vitro investigation of the implant-soft tissue interface is usually carried out using a monolayer cell-culture model that lacks a polarized-cell phenotype. This study developed a tissue-engineered three-dimensional oral mucosal model (3D OMM) to investigate the implant-soft tissue interface.
Susceptibility of Enterococcus faecalis biofilm to antibiotics and calcium hydroxide

Chai WL, Hamimah H, Cheng SC, Sallam AA, Abdullah M

J Oral Sci, 2007 Jun;49(2):161-6.
PMID: 17634730

The purpose of this study was to investigate the antimicrobial efficacy of six groups of antibiotics and calcium hydroxide against Enterococcus faecalis biofilm in a membrane filter model. Two-day-old E. faecalis (ATCC 29212) biofilm was exposed to ampicillin, co-trimoxazole, erythr omycin, oxytetracycline, vancomycin, vancomycin followed by gentamicin, Ca(OH)(2), and phosphate-buffered saline (control). After 1 h of exposure, the antimicrobial activity was neutralized by washing each disc five times in PBS, and then the colony-forming units of the remaining viable bacteria on each disc were counted. The results revealed that only erythromycin, oxytetracycline and Ca(OH)2 showed 100% biofilm kill. An ANOVA with a Bonferroni post hoc test (P < 0.05) detected significant differences among the test agents, except in the ampicillin group versus the co-trimoxazole group. It is concluded that erythromycin, oxytetracycline and Ca(OH)2 are 100% effective in eliminating E. faecalis biofilm, whereas ampicillin, co-trimoxazole, vancomycin, and vancomycin followed by gentamicin are ineffective.
Angiogenic effect of platelet-rich concentrates on dental pulp stem cells in inflamed microenvironment

Bindal P, Gnanasegaran N, Bindal U, Haque N, Ramasamy TS, Chai WL, et al.

Clin Oral Investig, 2019 Oct;23(10):3821-3831.
PMID: 30687907 DOI: 10.1007/s00784-019-02811-5

OBJECTIVE: In this study, we aimed to determine the suitable concentrations of human platelet lysate (HPL) and platelet-rich plasma (PRP) for maintaining the in vitro proliferative and angiogenic potential of inflamed dental pulp stem cells.
MATERIALS AND METHODS: Lipopolysaccharide (LPS)-induced inflamed dental pulp-derived stem cells (iDPSCs) were treated with different concentrations of HPL and PRP (10% and 20%) followed by determination of viability using Alamar Blue assay. Expression of angiogenesis-, adhesion-, and inflammation-regulating genes was also analyzed using RT-qPCR array. Furthermore, expression of growth factors at protein level in the cell culture microenvironment was measured using multiplex assay.
RESULTS: Viability of iDPSCs was significantly (p
Immune responses of human dental pulp stem cells in lipopolysaccharide-induced microenvironment

Bindal P, Ramasamy TS, Kasim NHA, Gnanasegaran N, Chai WL

Cell Biol Int, 2018 Jul;42(7):832-840.
PMID: 29363846 DOI: 10.1002/cbin.10938

This study aimed to investigate the effect of inflammatory stimuli on dental pulp stem cells (DPSCs) by assessing their proliferation and expression of genes as well as proteins in lipopolysaccharide (LPS)-induced microenvironment (iDPSCs). DPSCs were first characterized for their mesenchymal properties prior to challenging them with a series of LPS concentrations from 12 to 72 h. Following to this, their proliferation and inflammatory based genes as well as protein expression were assessed. iDPSCs had demonstrated significant expression of mesenchymal markers. Upon exposure to LPS, the viability dropped distinctly with increasing concentration, as compared to control (P

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