The Chicken Egg: An Advanced Material for Tissue Engineering.

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.

Bioengineered Salivary Gland Microtissues─A Review of 3D Cellular Models and their Applications.

Salivary glands (SGs) play a vital role in maintaining oral health through the production and release of saliva. Injury to SGs can lead to gland hypofunction and a decrease in saliva secretion manifesting as xerostomia. While symptomatic treatments for xerostomia exist, effective permanent solutions are still lacking, emphasizing the need for innovative approaches. Significant progress has been made in the field of three-dimensional (3D) SG bioengineering for applications in gland regeneration. This has been achieved through a major focus on cell culture techniques, including soluble cues and biomaterial components of the 3D niche. Cells derived from both adult and embryonic SGs have highlighted key in vitro characteristics of SG 3D models. While still in its first decade of exploration, SG spheroids and organoids have so far served as crucial tools to study SG pathophysiology. This review, based on a literature search over the past decade, covers the importance of SG cell types in the realm of their isolation, sourcing, and culture conditions that modulate the 3D microenvironment. We discuss different biomaterials employed for SG culture and the current advances made in bioengineering SG models using them. The success of these 3D cellular models are further evaluated in the context of their applications in organ transplantation and in vitro disease modeling.

Towards Precision Ophthalmology: The Role of 3D Printing and Bioprinting in Oculoplastic Surgery, Retinal, Corneal, and Glaucoma Treatment.

In the forefront of ophthalmic innovation, biomimetic 3D printing and bioprinting technologies are redefining patient-specific therapeutic strategies. This critical review systematically evaluates their application spectrum, spanning oculoplastic reconstruction, retinal tissue engineering, corneal transplantation, and targeted glaucoma treatments. It highlights the intricacies of these technologies, including the fundamental principles, advanced materials, and bioinks that facilitate the replication of ocular tissue architecture. The synthesis of primary studies from 2014 to 2023 provides a rigorous analysis of their evolution and current clinical implications. This review is unique in its holistic approach, juxtaposing the scientific underpinnings with clinical realities, thereby delineating the advantages over conventional modalities, and identifying translational barriers. It elucidates persistent knowledge deficits and outlines future research directions. It ultimately accentuates the imperative for multidisciplinary collaboration to enhance the clinical integration of these biotechnologies, culminating in a paradigm shift towards individualized ophthalmic care.

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.

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.

Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review.

This review aims to provide an understanding of the diagnostic and therapeutic challenges of uveitis associated with immune checkpoint inhibitors (ICI). In the wake of these molecules being increasingly employed as a treatment against different cancers, cases of uveitis post-ICI therapy have also been increasingly reported in the literature, warranting an extensive exploration of the clinical presentations, risk factors, and pathophysiological mechanisms of ICI-induced uveitis. This review further provides an understanding of the association between ICIs and uveitis, and assesses the efficacy of current diagnostic tools, underscoring the need for advanced techniques to enable early detection and accurate assessment. Further, it investigates the therapeutic strategies for ICI-related uveitis, weighing the benefits and limitations of existing treatment regimens, and discussing current challenges and emerging therapies in the context of their potential efficacy and side effects. Through an overview of the short-term and long-term outcomes, this article suggests recommendations and emphasizes the importance of multidisciplinary collaboration between ophthalmologists and oncologists. Finally, the review highlights promising avenues for future research and development in the field, potentially informing transformative approaches in the ocular assessment of patients under immunotherapy and the management of uveitis following ICI therapy.

Polymers and Biomaterials for Posterior Lamella of the Eyelid and the Lacrimal System.

The application of biopolymers in the reconstruction of the posterior lamella of the eyelid and the lacrimal system marks a significant fusion of biomaterial science with clinical advancements. This review assimilates research spanning 2015 to 2023 to provide a detailed examination of the role of biopolymers in reconstructing the posterior lamella of the eyelid and the lacrimal system. It covers the anatomy and pathophysiology of eyelid structures, the challenges of reconstruction, and the nuances of surgical intervention. This article progresses to evaluate the current gold standards, alternative options, and the desirable properties of biopolymers used in these intricate procedures. It underscores the advancements in the field, from decellularized grafts and acellular matrices to innovative natural and synthetic polymers, and explores their applications in lacrimal gland tissue engineering, including the promise of 3D bioprinting technologies. This review highlights the importance of multidisciplinary collaboration between material scientists and clinicians in enhancing surgical outcomes and patient quality of life, emphasizing that such cooperation is pivotal for translating benchtop research into bedside applications. This collaborative effort is vital for restoring aesthetics and functionality for patients afflicted with disfiguring eyelid diseases, ultimately aiming to bridge the gap between innovative materials and their clinical translation.

The Use of Functional Biomaterials in Aesthetic and Functional Restoration in Orbital Surgery.

The integration of functional biomaterials in oculoplastic and orbital surgery is a pivotal area where material science and clinical practice converge. This review, encompassing primary research from 2015 to 2023, delves into the use of biomaterials in two key areas: the reconstruction of orbital floor fractures and the development of implants and prostheses for anophthalmic sockets post-eye removal. The discussion begins with an analysis of orbital floor injuries, including their pathophysiology and treatment modalities. It is noted that titanium mesh remains the gold standard for orbital floor repair due to its effectiveness. The review then examines the array of materials used for orbital implants and prostheses, highlighting the dependence on surgeon preference and experience, as there are currently no definitive guidelines. While recent innovations in biomaterials show promise, the review underscores the need for more clinical data before these new materials can be widely adopted in clinical settings. The review advocates for an interdisciplinary approach in orbital surgery, emphasizing patient-centered care and the potential of biomaterials to significantly enhance patient outcomes.

Advances in Sjögren's Syndrome Dry Eye Diagnostics: Biomarkers and Biomolecules beyond Clinical Symptoms.

Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE.

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.

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.

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.

Advancements in Wearable and Implantable Intraocular Pressure Biosensors for Ophthalmology: A Comprehensive Review.

Glaucoma, marked by its intricate association with intraocular pressure (IOP), stands as a predominant cause of non-reversible vision loss. In this review, the physiological relevance of IOP is detailed, alongside its potential pathological consequences. The review further delves into innovative engineering solutions for IOP monitoring, highlighting the latest advancements in wearable and implantable sensors and their potential in enhancing glaucoma management. These technological innovations are interwoven with clinical practice, underscoring their real-world applications, patient-centered strategies, and the prospects for future development in IOP control. By synthesizing theoretical concepts, technological innovations, and practical clinical insights, this review contributes a cohesive and comprehensive perspective on the IOP biosensor's role in glaucoma, serving as a reference for ophthalmological researchers, clinicians, and professionals.

Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery.

Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and bioavailability. This necessitates frequent dosing, typically via eye drops or intravitreal injections, to manage diseases, often leading to side effects with long-term use. Suprachoroidal injection is a novel approach for targeted drug delivery to the posterior segment. The suprachoroidal space is the region between the sclera and the choroid and provides a potential route for minimally invasive medication delivery. Through a more targeted delivery to the posterior segment, this method offers advantages over other routes of administration, such as higher drug concentrations, increased bioavailability, and prolonged duration of action. Additionally, this approach minimizes the risk of corticosteroid-related adverse events such as cataracts and intraocular pressure elevation via compartmentalization. This review focuses on preclinical and clinical studies published between 2019 and 2023, highlighting the potential of suprachoroidal injection in treating a variety of posterior segment diseases. However, to fully harness its potential, more research is needed to address current challenges and limitations, such as the need for technological advancements, refinement of injection techniques, and consideration of cost and accessibility factors. Future studies exploring its use in conjunction with biotech products, gene therapies, and cell-based therapies can lead to personalized treatments that can revolutionize the field of ophthalmology.

Mapping the Potential of Microfluidics in Early Diagnosis and Personalized Treatment of Head and Neck Cancers.

Head and neck cancers (HNCs) account for ~4% of all cancers in North America and encompass cancers affecting the oral cavity, pharynx, larynx, sinuses, nasal cavity, and salivary glands. The anatomical complexity of the head and neck region, characterized by highly perfused and innervated structures, presents challenges in the early diagnosis and treatment of these cancers. The utilization of sub-microliter volumes and the unique phenomenon associated with microscale fluid dynamics have facilitated the development of microfluidic platforms for studying complex biological systems. The advent of on-chip microfluidics has significantly impacted the diagnosis and treatment strategies of HNC. Sensor-based microfluidics and point-of-care devices have improved the detection and monitoring of cancer biomarkers using biological specimens like saliva, urine, blood, and serum. Additionally, tumor-on-a-chip platforms have allowed the creation of patient-specific cancer models on a chip, enabling the development of personalized treatments through high-throughput screening of drugs. In this review, we first focus on how microfluidics enable the development of an enhanced, functional drug screening process for targeted treatment in HNCs. We then discuss current advances in microfluidic platforms for biomarker sensing and early detection, followed by on-chip modeling of HNC to evaluate treatment response. Finally, we address the practical challenges that hinder the clinical translation of these microfluidic advances.

Immunomodulatory Macrophages Enable E-MNC Therapy for Radiation-Induced Salivary Gland Hypofunction.

A newly developed therapy using effective-mononuclear cells (E-MNCs) is reportedly effective against radiation-damaged salivary glands (SGs) due to anti-inflammatory and revascularization effects. However, the cellular working mechanism of E-MNC therapy in SGs remains to be elucidated. In this study, E-MNCs were induced from peripheral blood mononuclear cells (PBMNCs) by culture for 5-7 days in medium supplemented with five specific recombinant proteins (5G-culture). We analyzed the anti-inflammatory characteristics of macrophage fraction of E-MNCs using a co-culture model with CD3/CD28-stimulated PBMNCs. To test therapeutic efficacy in vivo, either E-MNCs or E-MNCs depleted of CD11b-positive cells were transplanted intraglandularly into mice with radiation-damaged SGs. Following transplantation, SG function recovery and immunohistochemical analyses of harvested SGs were assessed to determine if CD11b-positive macrophages contributed to tissue regeneration. The results indicated that CD11b/CD206-positive (M2-like) macrophages were specifically induced in E-MNCs during 5G-culture, and Msr1- and galectin3-positive cells (immunomodulatory macrophages) were predominant. CD11b-positive fraction of E-MNCs significantly inhibited the expression of inflammation-related genes in CD3/CD28-stimulated PBMNCs. Transplanted E-MNCs exhibited a therapeutic effect on saliva secretion and reduced tissue fibrosis in radiation-damaged SGs, whereas E-MNCs depleted of CD11b-positive cells and radiated controls did not. Immunohistochemical analyses revealed HMGB1 phagocytosis and IGF1 secretion by CD11b/Msr1-positive macrophages from both transplanted E-MNCs and host M2-macrophages. Thus, the anti-inflammatory and tissue-regenerative effects observed in E-MNC therapy against radiation-damaged SGs can be partly explained by the immunomodulatory effect of M2-dominant macrophage fraction.

Localized Drug Delivery Systems: An Update on Treatment Options for Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, with surgery, radiotherapy, chemotherapy, and immunotherapy being the primary treatment modalities. The treatment for HNSCC has evolved over time, due to which the prognosis has improved drastically. Despite the varied treatment options, major challenges persist. HNSCC chemotherapeutic and immunotherapeutic drugs are usually administered systemically, which could affect the patient's quality of life due to the associated side effects. Moreover, the systemic administration of salivary stimulating agents for the treatment of radiation-induced xerostomia is associated with toxicities. Localized drug delivery systems (LDDS) are gaining importance, as they have the potential to provide non-invasive, patient-friendly alternatives to cancer therapy with reduced dose-limiting toxicities. LDDSs involve directly delivering a drug to the tissue or organ affected by the disease. Some of the common localized routes of administration include the transdermal and transmucosal drug delivery system (DDSs). This review will attempt to explore the different treatment options using LDDSs for the treatment of HNSCC and radiotherapy-induced damage and their potential to provide a better experience for patients, as well as the obstacles that need to be addressed to render them successful.

A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions.

The eye's intricate anatomical barriers pose significant challenges to the penetration, residence time, and bioavailability of topically applied medications, particularly in managing uveitis and neuro-ophthalmologic conditions. Addressing this issue, polymeric nano-based drug delivery systems (DDS) have surfaced as a promising solution. These systems enhance drug bioavailability in hard-to-reach target tissues, extend residence time within ocular tissues, and utilize biodegradable and nanosized polymers to reduce undesirable side effects. Thus, they have stimulated substantial interest in crafting innovative treatments for uveitis and neuro-ophthalmologic diseases. This review provides a comprehensive exploration of polymeric nano-based DDS used for managing these conditions. We discuss the present therapeutic hurdles posed by these diseases and explore the potential role of various biopolymers in broadening our treatment repertoire. Our study incorporates a detailed literature review of preclinical and clinical studies from 2017 to 2023. Owing to advancements in polymer science, ocular DDS has made rapid strides, showing tremendous potential to revolutionize the treatment of patients with uveitis and neuro-ophthalmologic disorders.

Protocol: carrageenan for the prevention of oral HPV infection - a feasibility randomised clinical trial.

INTRODUCTION: Head and neck cancers (HNCs) are a significant health burden worldwide. Oral human papillomavirus (HPV) infection is a major risk factor for HNCs. Unfortunately, currently available prophylactic vaccines have limited coverage and potential for HPV type replacement. Carrageenan, a natural product extracted from marine red algae, has demonstrated potency as an HPV inhibitor and could offer a potential alternative to prevent HPV-related diseases, including oral HPV infection. However, there is a lack of clinical studies on the effect of carrageenan on oral HPV infections. As a first step to address this gap, we propose a randomised controlled trial (RCT) to evaluate the feasibility of conducting a larger multicentric RCT to investigate the effect of a carrageenan mouthwash on oral HPV infection. METHODS AND ANALYSIS: We will conduct a placebo-controlled triple-blinded feasibility RCT with two parallel arms, each arm consisting of 20 participants. Participants will complete a single in-person visit at baseline and conduct biweekly follow-ups from home by completing a web-based questionnaire and sending saliva self-samples via mail. During the 6-month period trial, participants will gargle with the mouthwash morning and night, and around sexual activities. The study will evaluate several factors including recruitment and retention rates, the feasibility of data collection procedures, compliance with study procedures, acceptability of RCT procedures and intervention and safety data on carrageenan use in the oral cavity. We will estimate the standard deviation of outcome measures, including time to the incidence of oral HPV infection and time to clearance of prevalent oral HPV infection. The trial primary outcome is whether to proceed to a definitive trial based on prespecified progression criteria. ETHICS AND DISSEMINATION: The protocol was approved by the McGill University institutional review board. Study results will be presented at scientific conferences and published in academic journals. TRIAL REGISTRATION NUMBER: NCT05746988.