Uptake of Cyclodextrin Nanoparticles by Macrophages is Dependent on Particle Size and Receptor-Mediated Interactions.

Physiochemical properties of nanoparticles, such as their size and chemical composition, dictate their interaction with professional phagocytes of the innate immune system. Macrophages, in particular, are key regulators of the immune microenvironment that heavily influence particle biodistribution as a result of their uptake. This attribute enables macrophage-targeted delivery, including for phenotypic modulation. Saccharide-based materials, including polyglucose polymers and nanoparticles, are efficient vehicles for macrophage-targeted delivery. Here, we investigate the influence of particle size on cyclodextrin nanoparticle (CDNP) uptake by macrophages and further examine the receptor-mediated interactions that drive macrophage-targeted delivery. We designed and synthesized CDNPs ranging in size from 25 nm to >100 nm in diameter. Increasing particle size was correlated with greater uptake by macrophages in vitro. Both scavenger receptor A1 and mannose receptor were critical mediators of macrophage-targeted delivery, inhibition of which reduced the extent of uptake. Finally, we investigated the cellular bioavailability of drug-loaded CDNPs using a model anti-inflammatory drug, celastrol, which demonstrated that drug bioactivity is improved by CDNP loading relative to free drug alone. This study thus elucidates the interactions between the polyglucose nanoparticles and macrophages, thereby facilitating their application in macrophage-targeted drug delivery that has applications in the context of tissue injury and repair.

A Case of Advanced Oral Submucous Fibrosis Management: Beyond Conventional Approach.

A chronic, persistent, possibly cancerous condition that mostly affects the oral cavity is called oral submucous fibrosis (OSMF) and causes severe functional impairment. Due to its complex nature, OSMF requires a comprehensive strategy that includes both surgical and medication therapies. Multidisciplinary treatment was started, which included a complete stoppage of habit, dental hygiene precautions, dietary counselling, surgical intervention, supportive medicinal therapy, and physiotherapy. Following surgery and adjunct therapy, the patient's mouth opening and functional results were improved. The patient is kept for regular follow-up to assess the recurrence of fibrosis or any incidence of malignant transformation. This case emphasizes the difficulties in treating advanced OSMF and emphasizes how crucial it is to improve patient outcomes by early detection, stopping betel nut chewing, and thorough multidisciplinary care.

Understanding uptake of information about innovations among emergency department clinicians during the COVID-19 pandemic.

Objectives: Early in the COVID-19 pandemic, little was known about managing sick patients, but emergency department (ED) clinicians had to decide which treatments and care processes to adopt. Our objective was to describe how ED clinicians learned about innovations and how they assessed them for credibility during the pandemic. Methods: We purposively sampled clinicians from hospital-based EDs to conduct focus groups with ED clinicians and staff. We used both inductive and deductive approaches to conduct thematic analysis of transcripts. Results: We conducted focus groups with clinicians from eight EDs across the United States. We found that ED clinicians in our sample relied on friends and colleagues or departmental and institutional leadership for information on innovations. They used social media sources when they came from credible accounts but did not directly seek information from professional societies. Clinicians reported a range of challenges to obtain credible information during the pandemic, including a fractured and changing information environment, policies misaligned across clinical sites or that conflicted with clinical knowledge, high patient volume, fear of harming patients, and untimely information. Facilitators included access to experienced and trusted colleagues and leaders and practicing at multiple EDs. Conclusion: Participants cited anecdotal evidence, institutional practice, and word-of-mouth-rather than peer-reviewed evidence and professional society communications-as their primary sources of information about care innovations during the early phases of the pandemic. These results underscore the importance of developing trusted local mechanisms and wider networks to identify and vet information for frontline clinicians during rapidly emerging public health emergencies.

Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches.

Ischemic heart failure (IHF) is a leading cause of morbidity and mortality worldwide, for which heart transplantation remains the only definitive treatment. IHF manifests from myocardial infarction (MI) that initiates tissue remodeling processes, mediated by mechanical changes in the tissue (loss of contractility, softening of the myocardium) that are interdependent with cellular mechanisms (cardiomyocyte death, inflammatory response). The early remodeling phase is characterized by robust inflammation that is necessary for tissue debridement and the initiation of repair processes. While later transition toward an immunoregenerative function is desirable, functional reorientation from an inflammatory to reparatory environment is often lacking, trapping the heart in a chronically inflamed state that perpetuates cardiomyocyte death, ventricular dilatation, excess fibrosis, and progressive IHF. Therapies can redirect the immune microenvironment, including biotherapeutic and biomaterial-based approaches. In this review, we outline these existing approaches, with a particular focus on the immunomodulatory effects of therapeutics (small molecule drugs, biomolecules, and cell or cell-derived products). Cardioprotective strategies, often focusing on immunosuppression, have shown promise in pre-clinical and clinical trials. However, immunoregenerative therapies are emerging that often benefit from exacerbating early inflammation. Biomaterials can be used to enhance these therapies as a result of their intrinsic immunomodulatory properties, parallel mechanisms of action (e.g., mechanical restraint), or by enabling cell or tissue-targeted delivery. We further discuss translatability and the continued progress of technologies and procedures that contribute to the bench-to-bedside development of these critically needed treatments.

Sports-related facial trauma in the Indian population - A systematic review.

Background: Sports injuries are a growing concern which requires immediate attention. Dental injuries are the most common type of orofacial injuries sustained during sports activities. Objectives: This study aims to review the prevalence of sports-related facial trauma in India, to identify the most common types of oro-facial injury incurred due to sports, and to assess the level of awareness regarding preventive measures used in sports. Methodology: The present review was performed in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines. All articles published from 2005 to 2019 on sports-related facial trauma were analyzed. PubMed, Google Scholar, and Cochrane reviews databases were searched using primary keywords. Results: A total of 24 articles published in the period of 2005-2019 were included. The prevalence of sports-related facial trauma was found to be the highest in the study conducted by Selva et al., in 2018, at a rate of 75%, whereas it was found to be minimal in the study conducted by Bali et al. in 2013. While the awareness of mouthguards was reported the highest in a study conducted by Ramagoni et al., in 2007. Conclusion: This study shows that there is a definite need to improve the awareness as well as the usage of protective gear, from the level of schooling, where children are introduced to sports. Prevention of sports-related facial trauma is essential to avoid the serious and lifelong consequences which could be the aftermath of such injuries.

Mandibular Ramus Fractures: A Case Series of Diversity in Rarity.

Mandibular ramus fracture is usually minimally displaced as it is surrounded by the medial pterygoid medially, masseter laterally, and the pterygomasseteric sling inferiorly. They are commonly caused either by road traffic accidents or interpersonal violence. Ramus fracture is usually seen in conjunction with other mandibular fractures and is seldom found alone. The ramus is located at the congregation of the dentate and the non-dentate parts of the mandible. Ramus fractures are generally managed by closed reduction when minimally displaced but this technique has its disadvantages like poor maintenance of oral hygiene and prolonged healing time. It can get fractured in various patterns. Owing to the presence of anatomical structures on either side of the ramus and the orientation of the fracture line, the treatment plan varies in each case to prevent paresthesia by preserving the inferior alveolar nerve. This article has demonstrated four distinct kinds of mandibular ramus fractures and their management with open reduction internal fixation (ORIF).

Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype.

Injectable hydrogels may be pre-formed through dynamic crosslinks, allowing for injection and subsequent retention in the tissue by shear-thinning and self-healing processes, respectively. These properties enable the site-specific delivery of encapsulated therapeutics; yet, the sustained release of small-molecule drugs and their cell-targeted delivery remains challenging due to their rapid diffusive release and non-specific cellular biodistribution. Herein, we develop an injectable hydrogel system composed of a macrophage-targeted nanoparticle (cyclodextrin nanoparticles, CDNPs) crosslinked by adamantane-modified hyaluronic acid (Ad-HA). The polymer-nanoparticle hydrogel uniquely leverages cyclodextrin's interaction with small molecule drugs to create a spatially discrete drug reservoir and with adamantane to yield dynamic, injectable hydrogels. Through an innovative two-step drug screening approach and examination of 45 immunomodulatory drugs with subsequent in-depth transcriptional profiling of both murine and human macrophages, we identify celastrol as a potent inhibitor of pro-inflammatory (M1-like) behavior that furthermore promotes a reparatory (M2-like) phenotype. Celastrol encapsulation within the polymer-nanoparticle hydrogels permitted shear-thinning injection and sustained release of drug-laden nanoparticles that targeted macrophages to modulate cell behavior for greater than two weeks in vitro. The modular hydrogel system is a promising approach to locally modulate cell-specific phenotype in a range of applications for immunoregenerative medicine.

Polymeric materials for immune engineering: Molecular interaction to biomaterial design.

Biomaterials continue to evolve as complex engineered tools for interactively instructing biological systems, aiding in the understanding and treatment of various disease states through intimate biological interaction. The immune response to polymeric materials is a critical area of study, as it governs the body's response to biomaterial implants, drug delivery vehicles, and even therapeutic drug formulations. Importantly, the development of the immune response to polymeric biomaterials spans length scales - from single molecular interactions to the complex sensing of bulk biophysical properties, all of which coordinate a tissue- and systems-level response. In this review, we specifically discuss a bottom-up approach to designing biomaterials that use molecular-scale interactions to drive immune response to polymers and discuss how these interactions can be leveraged for biomaterial design. STATEMENT OF SIGNIFICANCE: The immune system is an integral controller of (patho)physiological processes, affecting nearly all aspects of human health and disease. Polymeric biomaterials, whether biologically derived or synthetically produced, can potentially alter the behavior of immune cells due to their molecular-scale interaction with individual cells, as well as their interpretation at the bulk scale. This article reviews common mechanisms by which immune cells interact with polymers at the molecular level and discusses how these interactions are being leveraged to produce the next generation of biocompatible and immunomodulatory materials.

Sectional impression tray and sectional denture for a microstomia patient.

Microstomia presents a unique challenge to the patient. Patients with microstomia who must wear removable dental prostheses often face the difficulty of being unable to insert or remove the prosthesis because of the constricted opening of the oral cavity. A completely edentulous patient, who developed microstomia along with Raynaud's phenomenon induced by scleroderma, is presented. This clinical report describes a quick and easy method for fabrication of a sectional custom impression tray connected by press button and a sectional complete denture retained by magnets. A sectional denture that provides ease in placement and removal can be successfully used in clinical practice for treatment of microstomia patients.

Micro secure digital card: A novel method for denture identification.

AIM: Denture labeling is of vital significance in social and forensic scenario. Numerous published work have attempted to present best method for denture marking, however not all satisfy crucial requirement either in terms of cost or storage of large amount of information. Hence, this paper describes a simple, cheap, and feasible denture marking system using portable Micro Secure Digital (MicroSD) card. These cards are created to store, modify, and view large amount of information with mobile phones, which forms an important part in majority of household in India. MATERIALS AND METHODS: After try-in make a depression slightly wider than the size of the MicroSD card on the external lingual flange of the trial mandibular denture. Process the denture together with acrylic wax flap according to manufacturer's instructions. The acrylic flap is planned in such a way that it is well-flushed with surrounding areas and can be lifted on one side to access the card. MicroSD card is placed in the denture and flap is closed. CONCLUSION: The proposed method is simple, cheap, and can store large amount of information.

Lenticular card: a new method for denture identification.

AIM: The need for denture marking is important for forensic and social reasons in case patients need to be identified individually. Majority of the surface marking and inclusion techniques are expensive, time consuming, and do not permit the incorporation of large amounts of information. In this article, the method to include a lenticular identification card stood out from the currently available denture marking methods in various ways. The lenticular card stores the patient's information has two or more images that can be viewed by changing the angle of view. MATERIALS AND METHODS: The maxillary denture was processed according to the manufacturer's instructions. The lenticular identification card was incorporated in the external posterior buccal surface of the maxillary denture using salt and pepper technique. For testing of durability, denture with the identifier was placed in water for up to 4 months. CONCLUSION: The proposed method is simple, cheap, and can store a large amount of information, thus allowing quick identification of the denture wearer. The labels showed no sign of fading or deterioration.