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.

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.

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.

Advances in Medical Wearable Biosensors: Design, Fabrication and Materials Strategies in Healthcare Monitoring.

In the past decade, wearable biosensors have radically changed our outlook on contemporary medical healthcare monitoring systems. These smart, multiplexed devices allow us to quantify dynamic biological signals in real time through highly sensitive, miniaturized sensing platforms, thereby decentralizing the concept of regular clinical check-ups and diagnosis towards more versatile, remote, and personalized healthcare monitoring. This paradigm shift in healthcare delivery can be attributed to the development of nanomaterials and improvements made to non-invasive biosignal detection systems alongside integrated approaches for multifaceted data acquisition and interpretation. The discovery of new biomarkers and the use of bioaffinity recognition elements like aptamers and peptide arrays combined with the use of newly developed, flexible, and conductive materials that interact with skin surfaces has led to the widespread application of biosensors in the biomedical field. This review focuses on the recent advances made in wearable technology for remote healthcare monitoring. It classifies their development and application in terms of electrochemical, mechanical, and optical modes of transduction and type of material used and discusses the shortcomings accompanying their large-scale fabrication and commercialization. A brief note on the most widely used materials and their improvements in wearable sensor development is outlined along with instructions for the future of medical wearables.

Salivary Organotypic Tissue Culture: An Ex-vivo 3D Model for Studying Radiation-Induced Injury of Human Salivary Glands.

An organotypic tissue culture model can maintain the cellular and molecular interactions, as well as the extracellular components of a tissue ex vivo. Thus, this 3D model biologically mimics in vivo conditions better than commonly used 2D culture in vitro models. Here, we provide a detailed workflow for generating live 3D organotypic tissue slices from patient-derived freshly resected salivary glandular tissues. We also cover the processing of these tissues for various downstream applications like live-dead viability/cytotoxicity assay, FFPE sectioning and immunostaining, and RNA and protein extraction with a focus on the salivary gland radiation injury model. These procedures can be applied extensively to various solid organs and used for disease modeling for cancer research, radiation biology, and regenerative medicine.

Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands.

Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE's components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG.

Salivary Diagnostics in Pediatrics and the Status of Saliva-Based Biosensors.

Salivary biomarkers are increasingly being used as an alternative to diagnose and monitor the progression of various diseases due to their ease of use, on site application, non-invasiveness, and most likely improved patient compliance. Here, we highlight the role of salivary biosensors in the general population, followed by the application of saliva as a diagnostic tool in the pediatric population. We searched the literature for pediatric applications of salivary biomarkers, more specifically, in children from 0 to 18 years old. The use of those biomarkers spans autoimmune, developmental disorders, oncology, neuropsychiatry, respiratory illnesses, gastrointestinal disorders, and oral diseases. Four major applications of salivary proteins as biomarkers are: (1) dental health (caries, stress from orthodontic appliances, and gingivitis); (2) gastrointestinal conditions (eosinophilic esophagitis, acid reflux, appendicitis); (3) metabolic conditions (obesity, diabetes); and (4) respiratory conditions (asthma, allergic rhinitis, small airway inflammation, pneumonia). Genomics, metabolomics, microbiomics, proteomics, and transcriptomics, are various other classifications for biosensing based on the type of biomarkers used and reviewed here. Lastly, we describe the recent advances in pediatric biosensing applications using saliva. This work guides scientists in fabricating saliva-based biosensors by comprehensively overviewing the potential markers and techniques that can be employed.

Acute Pyelonephritis With Cullen's Sign Masquerading As Pancreatitis.

Cullen's sign is well described in the literature as subcutaneous ecchymosis in the periumbilical region. It is most commonly represented with acute pancreatitis. Recently, there have been many case reports associated with this sign to different clinical scenarios. A 61-year-old gentleman reported to the ED with left flank pain, intermittent fever, and a periumbilical ecchymosis on abdominal examination. Numerous tests were performed to rule out the likelihood of acute pancreatitis. The patient was diagnosed with acute pyelonephritis and received appropriate treatment. Cullen's sign should raise suspicions of retroperitoneal or intraabdominal abnormalities. While the pathophysiological process underlying the emergence of this symptom frequently signals retroperitoneal bleed, this is not always the case.

Dental 3D-Printing: Transferring Art from the Laboratories to the Clinics.

The rise of three-dimensional (3D) printing technology has changed the face of dentistry over the past decade. 3D printing is a versatile technique that allows the fabrication of fully automated, tailor-made treatment plans, thereby delivering personalized dental devices and aids to the patients. It is highly efficient, reproducible, and provides fast and accurate results in an affordable manner. With persistent efforts among dentists for refining their practice, dental clinics are now acclimatizing from conventional treatment methods to a fully digital workflow to treat their patients. Apart from its clinical success, 3D printing techniques are now employed in developing haptic simulators, precise models for dental education, including patient awareness. In this narrative review, we discuss the evolution and current trends in 3D printing applications among various areas of dentistry. We aim to focus on the process of the digital workflow used in the clinical diagnosis of different dental conditions and how they are transferred from laboratories to clinics. A brief outlook on the most recent manufacturing methods of 3D printed objects and their current and future implications are also discussed.

Biomimetic Aspects of Oral and Dentofacial Regeneration.

Biomimetic materials for hard and soft tissues have advanced in the fields of tissue engineering and regenerative medicine in dentistry. To examine these recent advances, we searched Medline (OVID) with the key terms "biomimetics", "biomaterials", and "biomimicry" combined with MeSH terms for "dentistry" and limited the date of publication between 2010-2020. Over 500 articles were obtained under clinical trials, randomized clinical trials, metanalysis, and systematic reviews developed in the past 10 years in three major areas of dentistry: restorative, orofacial surgery, and periodontics. Clinical studies and systematic reviews along with hand-searched preclinical studies as potential therapies have been included. They support the proof-of-concept that novel treatments are in the pipeline towards ground-breaking clinical therapies for orofacial bone regeneration, tooth regeneration, repair of the oral mucosa, periodontal tissue engineering, and dental implants. Biomimicry enhances the clinical outcomes and calls for an interdisciplinary approach integrating medicine, bioengineering, biotechnology, and computational sciences to advance the current research to clinics. We conclude that dentistry has come a long way apropos of regenerative medicine; still, there are vast avenues to endeavour, seeking inspiration from other facets in biomedical research.

Smart Hydrogels in Tissue Engineering and Regenerative Medicine.

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.