Hieu Michael Pham

Aims To evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on periodontal status through a systematic review and meta-analysis. Methods Nine databases were searched for clinical studies up to September 2024 to identify clinical studies comparing periodontal parameters such as probing depth (PD), clinical attachment level (CAL), marginal bone level (MBL), and gingival and plaque indices (GI and PI) between SSRI-users and non-users. Study selection, data extraction, and risk of bias assessment were performed independently by two authors. Random-effects meta-analyses of mean differences (MD) were performed. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of available evidence. Results Five cross-sectional studies, including a total of 1254 patients (54.15% females) and 13170 teeth, were included. The use of SSRIs was significantly associated with inferior MBL (MD, 0.10; 95% confidence interval, 0.01 to 0.20) compared to non-users. No significant differences were observed in PD, CAL, and GI between SSRI-users and non-users. The overall quality of evidence was low, and all studies presented a moderate risk of bias. Conclusions Based on a low level of available scientific evidence, the use of SSRIs has a marginal yet significant effect on MBL. However, there is no direct association between SSRIs usage and periodontal parameters such as PD, CAL, and GI. Nonetheless, further research is warranted.

The chicken egg, an excellent natural source of proteins, has been an overlooked native biomaterial with remarkable physicochemical, structural, and biological properties. Recently, with significant advances in biomedical engineering, particularly in the development of 3D in vitro platforms, chicken egg materials have increasingly been investigated as biomaterials due to their distinct advantages such as their low cost, availability, easy handling, gelling ability, bioactivity, and provision of a developmentally stimulating environment for cells. In addition, the chicken egg and its by-products can improve tissue engraftment and stimulate angiogenesis, making it particularly attractive for wound healing and tissue engineering applications. Evidence suggests that the egg white (EW), egg yolk (EY), and eggshell membrane (ESM) are great biomaterial candidates for tissue engineering, as their protein composition resembles mammalian extracellular matrix proteins, ideal for cellular attachment, cellular differentiation, proliferation, and survivability. Moreover, eggshell (ES) is considered an excellent calcium resource for generating hydroxyapatite (HA), making it a promising biomaterial for bone regeneration. This review will provide researchers with a concise yet comprehensive understanding of the chicken egg structure, composition, and associated bioactive molecules in each component and introduce up-to-date tissue engineering applications of chicken eggs as biomaterials.

Saliva production by salivary glands play a crucial role in oral health. The loss of salivary gland function could lead to xerostomia, a condition also known as dry mouth. Significant reduction in saliva production could lead to further complications such as difficulty in speech, mastication, and increased susceptibility to dental caries and oral infections and diseases. While some palliative treatments are available for xerostomia, there are no curative treatments to date. This study explores the use of Egg White Alginate (EWA), as an alternative scaffold to Matrigel^® for culturing 3D salivary gland cells. A protocol for an optimized EWA was established by comparing cell viability using 1%, 2%, and 3% alginate solution. The normal salivary simian virus 40-immortalized acinar cell (NS-SV-AC) and the submandibular gland-human-1 (SMG-hu-1) cell lines were also used to compare the spheroid formation and cell viability properties of both scaffold biomaterials; cell viability was observed over 10 days using a Live–Dead Cell Assay. Cell viability and spheroid size in 2% EWA was significantly greater than 1% and 3%. It is evident that EWA can support salivary cell survivability as well as form larger spheroids when compared to cells grown in Matrigel^®. However, further investigations are necessary as it is unclear if cultured cells were proliferating or aggregating.

Hydrogels have been used for a variety of biomedical applications; in tissue engineering, they are commonly used as scaffolds to cultivate cells in a three-dimensional (3D) environment allowing the formation of organoids or cellular spheroids. Egg white-alginate (EWA) is a novel hydrogel which combines the advantages of both egg white and alginate; the egg white material provides extracellular matrix (ECM)-like proteins that can mimic the ECM microenvironment, while alginate can be tuned mechanically through its ionic crosslinking property to modify the scaffold’s porosity, strength, and stiffness. In this study, a frozen calcium chloride (CaCl₂) disk technique to homogenously crosslink alginate and egg white hydrogel is presented for 2.5D culture of human salivary cells. Different EWA formulations were prepared and biologically evaluated as a spheroid-like structure platform. Although all five EWA hydrogels showed biocompatibility, the EWA with 1.5% alginate presented the highest cell viability, while EWA with 3% alginate promoted the formation of larger size salivary spheroid-like structures. Our EWA hydrogel has the potential to be an alternative 3D culture scaffold that can be used for studies on drug-screening, cell migration, or as an in vitro disease model. In addition, EWA can be used as a potential source for cell transplantation (i.e., using this platform as an ex vivo environment for cell expansion). The low cost of producing EWA is an added advantage.

The field of regenerative medicine has tremendous potential for improved treatment outcomes and has been stimulated by advances made in bioengineering over the last few decades. The strategies of engineering tissues and assembling functional constructs that are capable of restoring, retaining, and revitalizing lost tissues and organs have impacted the whole spectrum of medicine and health care. Techniques to combine biomimetic materials, cells, and bioactive molecules play a decisive role in promoting the regeneration of damaged tissues or as therapeutic systems. Hydrogels have been used as one of the most common tissue engineering scaffolds over the past two decades due to their ability to maintain a distinct 3D structure, to provide mechanical support for the cells in the engineered tissues, and to simulate the native extracellular matrix. The high water content of hydrogels can provide an ideal environment for cell survival, and structure which mimics the native tissues. Hydrogel systems have been serving as a supportive matrix for cell immobilization and growth factor delivery. This review outlines a brief description of the properties, structure, synthesis and fabrication methods, applications, and future perspectives of smart hydrogels in tissue engineering.

Three-dimensional (3D) printing is an emerging technology in the field of dentistry. It uses a layer-by-layer manufacturing technique to create scaffolds that can be used for dental tissue engineering applications. While several 3D printing methodologies exist, such as selective laser sintering or fused deposition modeling, this paper will review the applications of 3D printing for craniofacial tissue engineering; in particular for the periodontal complex, dental pulp, alveolar bone, and cartilage. For the periodontal complex, a 3D printed scaffold was attempted to treat a periodontal defect; for dental pulp, hydrogels were created that can support an odontoblastic cell line; for bone and cartilage, a polycaprolactone scaffold with microspheres induced the formation of multiphase fibrocartilaginous tissues. While the current research highlights the development and potential of 3D printing, more research is required to fully understand this technology and for its incorporation into the dental field.

Nanotechnology is an exciting and innovative field when combined with tissue engineering, as it offers greater versatility in scaffold design for promoting cell adhesion, proliferation, and differentiation. The use of nanomaterials in craniofacial tissue regeneration is a newly developing field that holds great potential for treating craniofacial defects. This review presents an overview of the nanomaterials used for craniofacial tissue regeneration as well as their clinical applications for periodontal, vascular (endodontics), cartilage (temporomandibular joint), and bone tissue regeneration (dental implants and mandibular defects). To enhance periodontal tissue regeneration, nanohydroxyapatite was used in conjunction with other scaffold materials, such as polylactic acid, poly (lactic-co-glycolic acid), polyamide, chitosan, and polycaprolactone. To facilitate pulp regeneration along with the revascularization of the periapical tissue, polymeric nanofibers were used to simulate extracellular matrix formation. For temporomandibular joint (cartilage) engineering, nanofibrous-type and nanocomposite-based scaffolds improved tissue growth, cell differentiation, adhesion, and synthesis of cartilaginous extracellular matrix. To enhance bone regeneration for dental implants and mandibular bone defects, nanomaterials such as nanohydroxyapatite composite scaffolds, nanomodified mineral trioxide aggregate, and graphene were tested. Although the scientific knowledge in nanomaterials is rapidly advancing, there remain many unexplored data regarding their standardization, safety, and interactions with the nanoenvironment.

The efficacy of cisplatin (CIS) and 5-fluorouracil (5-FU) against squamous cell carcinomas of the head and neck (SCCHN) remains restricted due to their severe toxic side effects on non-cancer (normal) tissues. Recently, the broccoli extract sulforaphane (SF) was successfully tested as a combination therapy to target cancer cells. However, the effect of lower doses of CIS or 5-FU combined with SF on SCCHN remained unknown. This study tested the chemotherapeutic efficacies of SF combined with much lower doses of CIS or 5-FU against SCCHN cells aiming to reduce cytotoxicity to normal cells. Titrations of SF standalone or in combination with CIS and 5-FU were tested on SCCHN human cell lines (SCC12 and SCC38) and non-cancerous human cells (fibroblasts, gingival, and salivary cells). Concentrations of SF tested were comparable to those found in the plasma following ingestion of fresh broccoli sprouts. The treatment effects on cell viability, proliferation, DNA damage, apoptosis, and gene expression were measured. SF reduced SCCHN cell viability in a time- and dose-dependent manner. SF-combined treatment increased the cytotoxic activity of CIS by twofolds and of 5-FU by tenfolds against SCCHN, with no effect on non-cancerous cells. SF-combined treatment inhibited SCCHN cell clonogenicity and post-treatment DNA repair. SF increased SCCHN apoptosis and this mechanism was due to a down-regulation of BCL2 and up-regulation of BAX, leading to an up-regulation of Caspase3. In conclusion, combining SF with low doses of CIS or 5-FU increased cytotoxicity against SCCHN cells, while having minimal effects on normal cells.