Recent progress in regenerative therapy for damaged salivary glands: From bench to bedside.

OBJECTIVE: For functional restoration of salivary glands (SGs) injured by radiation therapy or Sjögren's syndrome (SS), various experimental approaches, such as gene therapy, tissue engineering, and cell-based therapy, have been proposed. This narrative review summarized recent progresses in research using cell-based therapies, including promising trials that could lead to bench-to-clinic applications. METHODS: A literature review based on PubMed publications in the last two decades was performed to summarize progresses in cell-based therapies for SG dysfunction. RESULTS: Over 100 experimental studies have shown the therapeutic potential of several types of cells, such as SG stem cells and mesenchymal stem cells, as well as effectively conditioned mononuclear cells, in both radiation injury and SS animal models. These therapies affect to slow fibrosis progression and stimulate tissue regeneration in atrophic glands. However, to date, only a total of seven studies have been developed to the stage of clinical study, showing the safety and preliminary efficacy. CONCLUSION: To lead the radical effectiveness expected in cell-based therapy, advances in reverse translational research and in innovative experimental research, based on the findings of recent clinical studies, will be critical in the next decade.

Nonspecific Orbital Inflammation (NSOI): Unraveling the Molecular Pathogenesis, Diagnostic Modalities, and Therapeutic Interventions.

Nonspecific orbital inflammation (NSOI), colloquially known as orbital pseudotumor, sometimes presents a diagnostic and therapeutic challenge in ophthalmology. This review aims to dissect NSOI through a molecular lens, offering a comprehensive overview of its pathogenesis, clinical presentation, diagnostic methods, and management strategies. The article delves into the underpinnings of NSOI, examining immunological and environmental factors alongside intricate molecular mechanisms involving signaling pathways, cytokines, and mediators. Special emphasis is placed on emerging molecular discoveries and approaches, highlighting the significance of understanding molecular mechanisms in NSOI for the development of novel diagnostic and therapeutic tools. Various diagnostic modalities are scrutinized for their utility and limitations. Therapeutic interventions encompass medical treatments with corticosteroids and immunomodulatory agents, all discussed in light of current molecular understanding. More importantly, this review offers a novel molecular perspective on NSOI, dissecting its pathogenesis and management with an emphasis on the latest molecular discoveries. It introduces an integrated approach combining advanced molecular diagnostics with current clinical assessments and explores emerging targeted therapies. By synthesizing these facets, the review aims to inform clinicians and researchers alike, paving the way for molecularly informed, precision-based strategies for managing NSOI.

Advancements in Nanosystems for Ocular Drug Delivery: A Focus on Pediatric Retinoblastoma.

The eye's complex anatomical structures present formidable barriers to effective drug delivery across a range of ocular diseases, from anterior to posterior segment pathologies. Emerging as a promising solution to these challenges, nanotechnology-based platforms-including but not limited to liposomes, dendrimers, and micelles-have shown the potential to revolutionize ophthalmic therapeutics. These nanocarriers enhance drug bioavailability, increase residence time in targeted ocular tissues, and offer precise, localized delivery, minimizing systemic side effects. Focusing on pediatric ophthalmology, particularly on retinoblastoma, this review delves into the recent advancements in functionalized nanosystems for drug delivery. Covering the literature from 2017 to 2023, it comprehensively examines these nanocarriers' potential impact on transforming the treatment landscape for retinoblastoma. The review highlights the critical role of these platforms in overcoming the unique pediatric eye barriers, thus enhancing treatment efficacy. It underscores the necessity for ongoing research to realize the full clinical potential of these innovative drug delivery systems in pediatric ophthalmology.

Simulation training for medical emergencies: Evaluation of dentists' long-term learning skills and confidence.

INTRODUCTION: As the population ages and more patients experience medical emergencies during dental treatments, dentists must competently and confidently manage these situations. We developed a simulation training course for medical emergencies in the dental setting using an inexpensive vital sign simulation app for smartphones/tablets without the need for an expensive simulator. However, the duration for which this effect is maintained is unclear. This study was performed to evaluate the long-term educational effect at 3, 6, and 12 months after taking the course. MATERIALS AND METHODS: Thirty-nine dental residents participated in this course. Scenarios included vasovagal syncope, anaphylaxis, hyperventilation syndrome, and acute coronary syndrome, each of which the participants had to diagnose and treat. The participants were evaluated using a checklist for anaphylaxis diagnosis and treatment skills immediately after and 3, 6, and 12 months after the course. The participants were also surveyed about their confidence in diagnosing and treating these conditions by questionnaire before, immediately after, and 3, 6, and 12 months after the course. RESULTS: The checklist scores for anaphylaxis were significantly lower at 3, 6, and 12 months after the course than immediately after the course. The percentage of participants who provided a correct diagnosis and appropriate treatment for vasovagal syncope, hyperventilation syndrome, and acute coronary syndrome was lower at all reassessments than immediately after the course. CONCLUSION: Because medical emergency management skills and confidence declined within 3 months, it would be useful to introduce a refresher course approximately 3 months after the initial course to maintain skills and confidence.

Gene Therapeutic Delivery to the Salivary Glands.

The salivary glands, exocrine glands in our body producing saliva, can be easily damaged by various factors. Radiation therapy and Sjogren's syndrome (a systemic autoimmune disease) are the two main causes of salivary gland damage, leading to a severe reduction in patients' quality of life. Gene transfer to the salivary glands has been considered a promising approach to treating the dysfunction. Gene therapy has long been applied to cure multiple diseases, including cancers, and hereditary and infectious diseases, which are proven to be safe and effective for the well-being of patients. The application of this treatment on salivary gland injuries has been studied for decades, yet its clinical progress is delayed. This chapter provides a coup d'oeil into gene transfer methods and various gene/vector types for salivary glands to help the new scientists and update established scientists on the progress that has been made during the past decades for the treatment of salivary gland disorders.

Drug Therapeutics Delivery to the Salivary Glands: Intraglandular and Intraductal Injections.

Salivary gland hypofunction and xerostomia following pathological conditions like Sjogren's syndrome or head and neck radiotherapy usually lead to tremendous impairment of oral health, speech, and swallowing. The use of systemic drugs to alleviate the symptoms of these conditions has been associated with various adverse effects. Techniques of local drug delivery to the salivary gland have grown enormously to address this problem properly. The techniques include intraglandular and intraductal injections. In this chapter, we will provide a review of the literature for both techniques while incorporating our lab experience in using them.

Retinal Prostheses: Engineering and Clinical Perspectives for Vision Restoration.

A retinal prosthesis, also known as a bionic eye, is a device that can be implanted to partially restore vision in patients with retinal diseases that have resulted in the loss of photoreceptors (e.g., age-related macular degeneration and retinitis pigmentosa). Recently, there have been major breakthroughs in retinal prosthesis technology, with the creation of numerous types of implants, including epiretinal, subretinal, and suprachoroidal sensors. These devices can stimulate the remaining cells in the retina with electric signals to create a visual sensation. A literature review of the pre-clinical and clinical studies published between 2017 and 2023 is conducted. This narrative review delves into the retinal anatomy, physiology, pathology, and principles underlying electronic retinal prostheses. Engineering aspects are explored, including electrode-retina alignment, electrode size and material, charge density, resolution limits, spatial selectivity, and bidirectional closed-loop systems. This article also discusses clinical aspects, focusing on safety, adverse events, visual function, outcomes, and the importance of rehabilitation programs. Moreover, there is ongoing debate over whether implantable retinal devices still offer a promising approach for the treatment of retinal diseases, considering the recent emergence of cell-based and gene-based therapies as well as optogenetics. This review compares retinal prostheses with these alternative therapies, providing a balanced perspective on their advantages and limitations. The recent advancements in retinal prosthesis technology are also outlined, emphasizing progress in engineering and the outlook of retinal prostheses. While acknowledging the challenges and complexities of the technology, this article highlights the significant potential of retinal prostheses for vision restoration in individuals with retinal diseases and calls for continued research and development to refine and enhance their performance, ultimately improving patient outcomes and quality of life.

Exploring the Potential of Nanoporous Materials for Advancing Ophthalmic Treatments.

The landscape of ophthalmology is undergoing significant transformations, driven by technological advancements and innovations in materials science. One of the advancements in this evolution is the application of nanoporous materials, endowed with unique physicochemical properties ideal for a variety of ophthalmological applications. Characterized by their high surface area, tunable porosity, and functional versatility, these materials have the potential to improve drug delivery systems and ocular devices. This review, anchored by a comprehensive literature focusing on studies published within the last five years, examines the applications of nanoporous materials in ocular drug delivery systems (DDS), contact lenses, and intraocular lenses. By consolidating the most current research, this review aims to serve as a resource for clinicians, researchers, and material scientists engaged in the rapidly evolving field of ophthalmology.

An Overview of the Dry Eye Disease in Sjögren's Syndrome Using Our Current Molecular Understanding.

Sjögren's syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren's syndrome dry eye (SSDE) from non-Sjögren's syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren's syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon.

Microfluidic Organ-on-A-chip: A Guide to Biomaterial Choice and Fabrication.

Organ-on-A-chip (OoAC) devices are miniaturized, functional, in vitro constructs that aim to recapitulate the in vivo physiology of an organ using different cell types and extracellular matrix, while maintaining the chemical and mechanical properties of the surrounding microenvironments. From an end-point perspective, the success of a microfluidic OoAC relies mainly on the type of biomaterial and the fabrication strategy employed. Certain biomaterials, such as PDMS (polydimethylsiloxane), are preferred over others due to their ease of fabrication and proven success in modelling complex organ systems. However, the inherent nature of human microtissues to respond differently to surrounding stimulations has led to the combination of biomaterials ranging from simple PDMS chips to 3D-printed polymers coated with natural and synthetic materials, including hydrogels. In addition, recent advances in 3D printing and bioprinting techniques have led to the powerful combination of utilizing these materials to develop microfluidic OoAC devices. In this narrative review, we evaluate the different materials used to fabricate microfluidic OoAC devices while outlining their pros and cons in different organ systems. A note on combining the advances made in additive manufacturing (AM) techniques for the microfabrication of these complex systems is also discussed.

Bioengineering in salivary gland regeneration.

Salivary gland (SG) dysfunction impairs the life quality of many patients, such as patients with radiation therapy for head and neck cancer and patients with Sjögren's syndrome. Multiple SG engineering strategies have been considered for SG regeneration, repair, or whole organ replacement. An in-depth understanding of the development and differentiation of epithelial stem and progenitor cells niche during SG branching morphogenesis and signaling pathways involved in cell-cell communication constitute a prerequisite to the development of suitable bioengineering solutions. This review summarizes the essential bioengineering features to be considered to fabricate an engineered functional SG model using various cell types, biomaterials, active agents, and matrix fabrication methods. Furthermore, recent innovative and promising approaches to engineering SG models are described. Finally, this review discusses the different challenges and future perspectives in SG bioengineering.

Saliva as a diagnostic specimen for SARS-CoV-2 detection: A scoping review.

OBJECTIVES: This scoping review aims to summarize the diagnostic value of saliva assessed from current studies that (1) compare its performance in reverse transcriptase-polymerase chain reaction testing to nasopharyngeal swabs, (2) evaluate its performance in rapid and point-of-care COVID-19 diagnostic tests, and (3) explore its use as a specimen for detecting anti-SARS-CoV-2 antibodies. MATERIALS AND METHODS: A systematic search was performed on the following databases: Medline and Embase (Ovid), World Health Organization, Centers for Disease Control and Prevention, and Global Health (Ovid) from January 2019 to September 2021. Of the 657 publications identified from the searches, n = 146 articles were included in the final scoping review. RESULTS: Our findings showcase that salivary samples exceed nasopharyngeal swabs in detecting SARS-CoV-2 using reverse transcriptase-polymerase chain reaction testing in several studies. A select number of rapid antigen and point-of-care tests from the literature were also identified capable of high detection rates using saliva. Moreover, anti-SARS-CoV-2 antibodies have been shown to be detectable in saliva through biochemical assays. CONCLUSION: We highlight the potential of saliva as an all-rounded specimen in detecting SARS-CoV-2. However, future large-scale clinical studies will be needed to support its widespread use as a non-invasive clinical specimen for COVID-19 testing.

In Vitro Toxicity Evaluation of Carrageenan on Cells and Tissues of the Oral Cavity.

Carrageenan is a highly potent anti-human papillomavirus (HPV) agent with the potential for formulation as a mouthwash against oral HPV infection. However, its toxic effect on tissues of the oral cavity is currently unknown. This study aims to evaluate the safety of carrageenan on human cells and tissues of the oral cavity. Human salivary gland cells and reconstructed human oral epithelium (RHOE) were used for this in vitro study. The cells were subjected to 0.005-100 µg/mL of carrageenan for 4, 12, and 24 h in quadruplicate. RHOE were exposed to 100 µg/mL of carrageenan for 24 h in triplicate and stained with hematoxylin/eosin for histological analyses. All experiments had saline and 1% sodium dodecyl sulphate (SDS) as negative and positive controls, respectively. Carrageenan tissue toxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to quantify cell viability. Tissue toxicity was further evaluated histologically by an oral pathologist to assess morphological changes. Our data showed that carrageenan did not significantly decrease cell and tissue viability when compared to the positive control. The histological evaluation of the RHOE also showed no loss of viability of the carrageenan-treated sample compared to untreated tissue. In contrast, 1% SDS-treated RHOE showed extensive tissue destruction. Our experiments suggest that carrageenan is safe for use in the oral cavity.

Axolotls' and Mices' Oral-Maxillofacial Trephining Wounds Heal Differently.

The Ambystoma maxicanum (axolotl) regenerates strikingly from wounds and amputations. Comparing its healing ability to non-regenerative species such as the mouse should help narrow in on mechanisms to improve human wound healing. Here, the tongue and intermandibular soft tissues of both mice (C57BL/6NCrl) and axolotls were wounded with a 2-2.5 mm punch biopsy. The study aimed to compare the differences between these 2 species following surgical resection with regard to the macroscopic and histological characteristics. These include wound closure times, epithelial wound sealing and thickness as well as acute immune marker myeloperoxidase (MPO) response over 30 days. Post surgery, mice visually showed greater haemorrhage; their wounds immediately collapsed while it took 14 days for the axolotls mandibular void to close. The epithelium sealed the axolotls' wound margins within 24 h with a maximal mean thickness of 0.42 ± 0.13-fold normalized to unwounded skin. In mice, the epithelium separately sealed the ventral and dorsal sides, respectively at 7 and 7-30 days with mean maximal epithelial thicknesses reaching 13 ± 5.6 and 3.0 ± 0.63-fold. Mean MPO-positive cell values peaked in axolotls at 14 ± 1.5-fold between hours 6-12; while in mice, it peaked at 8.7 ± 0.9-fold between hours 24-96. We conclude that axolotls form smaller blood clots, have a faster and thinner epithelial cell migrating front, and a shorter MPO-positive cell response in comparison to mice. These observations may help refine future oral and facial wound-healing research and treatment.

Titanium-Containing Silicate-Based Sol-Gel Bioactive Glass: Development, Characterization, and Applications.

Bioactive glasses are surface-reactive glasses that, when placed in physiological fluid, undergo a transformation from glass to hydroxyapatite. Doping the bioactive glass with metallic ions can impart desirable and unique properties that are not inherent to natural hydroxyapatite. Once such ion is titanium. Titanium exists in trace amounts in native dental enamel, and its presence has been correlated with increased tooth hardness and brightness, both desirable clinical properties. Synthetic titanium-substituted hydroxyapatite exhibits better mechanical and antibacterial properties and demonstrates potential for an improved cellular response when compared to unmodified hydroxyapatite with applications in the broader field of bone tissue engineering. In this work, we use the sol-gel method to synthesize a titanium-containing silicate-based bioactive glass aimed at generating titanium-substituted hydroxyapatite on the glass surface upon immersion in body fluid. Titanium is homogeneously distributed throughout our glass, which keeps its amorphous nature. After 14 days of immersion in simulated body fluid, the glass forms a titanium-substituted hydroxyapatite on its surface. Enamel surfaces treated with the titanium-containing glass show significantly increased microhardness compared to enamel surfaces treated with a control glass, confirming the potential for the proposed glass in enamel remineralization. We also show that the presence of titanium in the glass promotes cell differentiation toward bone formation, suggesting further applications for this material in the broader field of bone tissue engineering.

Differences in platelet-rich plasma composition influence bone healing.

AIM: Platelet-rich plasma (PRP) is an autologous blood-derived material that has been used to enhance bone regeneration. Clinical studies, however, reported inconsistent outcomes. This study aimed to assess the effect of changes in leucocyte and PRP (L-PRP) composition on bone defect healing. MATERIALS AND METHODS: L-PRPs were prepared using different centrifugation methods and their regenerative potential was assessed in an in-vivo rat model. Bilateral critical-size tibial bone defects were created and filled with single-spin L-PRP, double-spin L-PRP, or filtered L-PRP. Empty defects and defects treated with collagen scaffolds served as controls. Rats were euthanized after 2 weeks, and their tibias were collected and analysed using micro-CT and histology. RESULTS: Double-spin L-PRP contained higher concentrations of platelets than single-spin L-PRP and filtered L-PRP. Filtration of single-spin L-PRP resulted in lower concentrations of minerals and metabolites. In vivo, double-spin L-PRP improved bone healing by significantly reducing the size of bone defects (1.08 ± 0.2 mm3 ) compared to single-spin L-PRP (1.42 ± 0.27 mm3 ) or filtered L-PRP (1.38 ± 0.28 mm3 ). There were fewer mast cells, lymphocytes, and macrophages in defects treated with double-spin L-PRP than in those treated with single-spin or filtered L-PRP. CONCLUSION: The preparation method of L-PRP affects their composition and potential to regenerate bone.

Tracking of Oral and Craniofacial Stem Cells in Tissue Development, Regeneration, and Diseases.

PURPOSE OF REVIEW: The craniofacial region hosts a variety of stem cells, all isolated from different sources of bone and cartilage. However, despite scientific advancements, their role in tissue development and regeneration is not entirely understood. The goal of this review is to discuss recent advances in stem cell tracking methods and how these can be advantageously used to understand oro-facial tissue development and regeneration. RECENT FINDINGS: Stem cell tracking methods have gained importance in recent times, mainly with the introduction of several molecular imaging techniques, like optical imaging, computed tomography, magnetic resonance imaging, and ultrasound. Labelling of stem cells, assisted by these imaging techniques, has proven to be useful in establishing stem cell lineage for regenerative therapy of the oro-facial tissue complex. Novel labelling methods complementing imaging techniques have been pivotal in understanding craniofacial tissue development and regeneration. These stem cell tracking methods have the potential to facilitate the development of innovative cell-based therapies.

COVID-19's impact on private practice and academic dentistry in North America.

The COVID-19 pandemic is a major public health crisis for countries around the world. In response to this global outbreak, the World Health Organization declared a public health emergency of international concern. Dental professionals are especially at high risk of contracting the COVID-19 virus due to the unique nature of dentistry, more specifically, exposure to aerosols and droplets. When it comes to dental emergencies, it was crucial to maintain urgent dental care services operational to help reduce the burden on our healthcare system and hospitals already under pressure. The COVID-19 pandemic has significantly impacted how dentistry is practiced in North America in both the private practice and academic settings. This article shares the perspectives of dentists practicing in private practice and clinician-researchers in academic dental institutions. More specifically, we discuss about measures implemented to minimize risks of disease transmission, challenges in emergency dental care, impact on patients, as well as impact on the professional and personal lives of the dental team during the COVID-19 crisis.

Hydrogel Encapsulation of Mesenchymal Stem Cells and Their Derived Exosomes for Tissue Engineering.

Tissue engineering has been an inveterate area in the field of regenerative medicine for several decades. However, there remains limitations to engineer and regenerate tissues. Targeted therapies using cell-encapsulated hydrogels, such as mesenchymal stem cells (MSCs), are capable of reducing inflammation and increasing the regenerative potential in several tissues. In addition, the use of MSC-derived nano-scale secretions (i.e., exosomes) has been promising. Exosomes originate from the multivesicular division of cells and have high therapeutic potential, yet neither self-replicate nor cause auto-immune reactions to the host. To maintain their biological activity and allow a controlled release, these paracrine factors can be encapsulated in biomaterials. Among the different types of biomaterials in which exosome infusion is exploited, hydrogels have proven to be the most user-friendly, economical, and accessible material. In this paper, we highlight the importance of MSCs and MSC-derived exosomes in tissue engineering and the different biomaterial strategies used in fabricating exosome-based biomaterials, to facilitate hard and soft tissue engineering.

Correction: Abughanam, G., et al. Mesenchymal Stem Cells Extract (MSCsE)-Based Therapy Alleviates Xerostomia and Keratoconjunctivitis Sicca in Sjogren's Syndrome-Like Disease. Int. J. Mol. Sci. 2019, 20, 4750.

The authors wish to make the following corrections to this paper [...].