Microneedles for painless transdermal immunotherapeutic applications

Immunotherapy has recently garnered plenty of attention to improve the clinical outcomes in the treatment of various diseases. However, owing to the dynamic nature of the immune system, this approach has often been challenged by concerns regarding the lack of adequate long-term responses in patients. The development of microneedles (MNs) has resulted in the improvement and expansion of immuno-reprogramming strategies due to the housing of high accumulation of dendritic cells, macrophages, lymphocytes, and mast cells in the dermis layer of the skin. In addition, MNs possess many outstanding properties, such as the ability for the painless traverse of the stratum corneum, minimal invasiveness, facile fabrication, excellent biocompatibility, convenient administration, and bypassing the first pass metabolism that allows direct translocation of therapeutics into the systematic circulation. These advantages make MNs excellent candidates for the delivery of immunological biomolecules to the dermal antigen-presenting cells in the skin with the aim of vaccinating or treating different diseases, such as cancer and autoimmune disorders, with minimal invasiveness and side effects. This review discusses the recent advances in engineered MNs and tackles limitations relevant to traditional immunotherapy of various hard-to-treat diseases.Peer reviewe

Emerging Strategies to Bypass Transplant Rejection via Biomaterial-Assisted Immunoengineering:Insights from Islets and Beyond

Novel transplantation techniques are currently under development to preserve the function of impaired tissues or organs. While current technologies can enhance the survival of recipients, they have remained elusive to date due to graft rejection by undesired in vivo immune responses despite systemic prescription of immunosuppressants. The need for life-long immunomodulation and serious adverse effects of current medicines, the development of novel biomaterial-based immunoengineering strategies has attracted much attention lately. Immunomodulatory 3D platforms can alter immune responses locally and/or prevent transplant rejection through the protection of the graft from the attack of immune system. These new approaches aim to overcome the complexity of the long-term administration of systemic immunosuppressants, including the risks of infection, cancer incidence, and systemic toxicity. In addition, they can decrease the effective dose of the delivered drugs via direct delivery at the transplantation site. In this review, we comprehensively address the immune rejection mechanisms, followed by recent developments in biomaterial-based immunoengineering strategies to prolong transplant survival. We also compare the efficacy and safety of these new platforms with conventional agents. Finally, challenges and barriers for the clinical translation of the biomaterial-based immunoengineering transplants and prospects are discussed

Nanostructured multifunctional stimuli-responsive glycopolypeptide-based copolymers for biomedical applications

Inspired by natural resources, such as peptides and carbohydrates, glycopolypeptide biopolymer has recently emerged as a new form of biopolymer being recruited in various biomedical applications. Glycopolypeptides with well-defined secondary structures and pendant glycosides on the polypeptide backbone have sparked lots of research interest and they have an innate ability to self-assemble in diverse structures. The nanostructures of glycopolypeptides have also opened up new perspectives in biomedical applications due to their stable three-dimensional structures, high drug loading efficiency, excellent biocompatibility, and biodegradability. Although the development of glycopolypeptide-based nanocarriers is well-studied, their clinical translation is still limited. The present review highlights the preparation and characterization strategies related to glycopolypeptides-based copolymers, followed by a comprehensive discussion on their biomedical applications with a specific focus on drug delivery by various stimuli-responsive (e.g., pH, redox, conduction, and sugar) nanostructures, as well as their beneficial usage in diagnosis and regenerative medicine.Peer reviewe

Evaluation of Factors Affecting the Efficacy of Nitroglycerin Infusion in Patients with Hypertensive Crisis: Effects of nitroglycerin in hypertensive crisis

Hypertensive crisis is a severe elevation in blood pressure (BP) that requires urgent reduction in BP to prevent or reduce target organ damage. The antihypertensive effects of nitroglycerin have been proven, but there are limited reports on the effects of various factors on the effectiveness of nitroglycerin in the treatment of hypertensive crisis. The purpose of this study was to evaluate the effects of diabetes, history of hypertension and age as well as gender differences in the effectiveness of nitroglycerin in patients with hypertensive crisis. This study included 76 patients with hypertensive crisis. For management, nitroglycerin initially started at 5 μg/min by intravenous infusion and, if needed, every 3 to 5 min, 5 μg/min was added to the above dose to a maximum of 20 μg/min as long as the blood pressure level reaches to the desired level. The results showed that the mean time of reduction of BP to the desired level in patients with history of hypertension and diabetes alone or both diseases, increased significantly in comparison to patients without these underlying diseases (P<0.01, P<0.01 and P<0.05 respectively). The results also demonstrated that there is a significant difference between patients younger than 45 and over 65 years with patients aged 45-65 (P<0.05). There is no difference between two genders in each group (P>0.05). In conclusion, patients with diabetes and/or history of hypertension are more resistant to pressure lowering effect of nitroglycerin in hypertensive crisis. Patients under 45 years of age as well as the elderly are also resistant. Therefore, it is advisable for physicians to choose the appropriate treatment for the desired outcome, considering the patient's condition

Dermal Wound Healing

Recent Progress in Conductive Biomaterials for Tissue Engineering. Intrinsically conducting polymers and their derivatives are being employed in tissue engineering due to their promising electrical conductivity as bioactive scaffolds for tissue regeneration (i.e., bone, nerve, muscle and cardiac tissue engineering and wound healing). Nevertheless, their mechanical brittleness and poor processability limit their applications, resulting in the development of composites, which are based on conductive polymers. The main objective of this book is to summarize and review the preparation methods; physicochemical and mechanical properties; biological properties; and latest advances of both conductive polymers and their composites for tissue engineering applications. Researchers, scientists, and upper level students working in the areas of biomedical engineering, polymers, and biomaterials science will find Electrically Conducting Polymers and Their Composites for Tissue Engineering to be an essential reference.</p

Effects of pre-treatment with metoprolol and diltiazem on cerebral ischemia/reperfusion-induced injuries

Stroke is one of the most important health concerns worldwide. Calcium ions accumulation in the nerve cells and increase in the catecholamines level of the brain following cerebral ischemia/reperfusion (I/R) are accompanied by damaging effects. Therefore, the present study aimed to evaluate the effects of diltiazem, as a calcium channel blocker, and metoprolol, as a β-adrenoceptors antagonist, on I/R injury. In this study, 30 male Wistar rats were divided into control, I/R, metoprolol, diltiazem, and metoprolol plus diltiazem groups (n=6 in each). Metoprolol (1 mg/kg/day) and diltiazem (5 mg/kg/day) were injected intraperitoneally (i.p.) for 7 days before I/R induction. On day 8, the animals underwent ischemia by bilateral common carotid arteries occlusion for 20 min. Histopathological analysis showed a significant reduction in leukocyte infiltration in diltiazem, metoprolol, and diltiazem plus metoprolol treated rats compared with the I/R group (P&lt;0.05, P&lt;0.01, P&lt;0.01, respectively). In addition, in all treated groups, myeloperoxidase activity and malondialdehyde levels in the brain tissue significantly declined compared with the I/R group (P&lt;0.001). Furthermore, pre-treatment with diltiazem and metoprolol alone or in co-administration remarkably reduced infarct size following I/R (P&lt;0.001). Overall, the results indicate the considerable neuroprotective effects of metoprolol and diltiazem in cerebral I/R

Protective Effects of Memantine, an NMDA Receptor Antagonist, Against Cerebral Ischemia/Reperfusion Induced Injuries in Rats with Transient Congenital Hypothyroidism: Neuroprotective effects of memantine in hypothyroidism

Stroke is one of the major causes of mortality worldwide. Memantine, an NMDA receptor antagonist, has protective effects on neuronal cells and is important candidate as a neuroprotective agent in cerebral ischemia. On the other hand, thyroid hormones are one of the important factors in the development of the central nervous system (CNS) and its activity and the long-term adverse effects of transient thyroid function abnormalities at birth on intellectual development has been proven. Therefore, the aim of the present study was to evaluate the effects of memantine on cerebral ischemia/reperfusion (I/R) induced injuries in transient congenital hypothyroidism (TCH). The adult male Wistar TCH rats (240±20 g) were underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Memantine (20 mg/kg) alone or in combination with vitamin C (200 mg/kg) were administered intraperitoneally (ip) for 7 days after cerebral ischemia. Then, histopathology, cerebral infarct size and malondialdehyde level were evaluated. Histopathological analysis showed that memantine significantly decreased leukocyte infiltration in comparison to I/R group (p&lt;0.01). Memantine also reduced infarct size and malondialdehyde level compared with I/R group (p&lt;0.01). Memantine and vitamin C combination group had no significant effects on leukocyte infiltration, infarct size and malondialdehyde level. Our results showed that memantine through reduction in leukocyte infiltration, lipid peroxidation and infarct size could reduce cerebral ischemia/reperfusion induced injuries in transient congenital hypothyroidism. Hence, memantine might be considered as a neuroprotective agent in hypothyroidism

The Eeffect of Metformin Combined with Calcium-Vitamin D3 Against Diet-Induced Nonalcoholic Fatty Liver Disease

Purpose: Metformin is one of the most popular drugs tested against nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D3 cosupplementation will intensify the effect of metformin on the prevention of high-fat, high-fructose (HFFr) diet-induced hepatic steatosis. Methods: Male wistar rats (210±16 g) were assigned into the following seven groups: a Control group to receive a standard chow and six HFFr-fed groups to receive diets containing either normal (0.5% calcium and 1000 IU/kg vitamin D3) or high amount of calcium and vitamin D3 (2.4% calcium and 10000 IU/kg vitamin D3) (CaD), in combination with gastric gavage administration of either saline or 25 or 200 mg/kg body weight/day metformin. After 60 days, rats were assessed with respect to their anthropometric, metabolic and hepatic parameters, as well as their hepatic AMP-activated protein kinase (AMPK) phosphorylation. Results: Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation. In addition, slightly (and non-significantly) better effects of the combination in ameliorating steatosis and hepatic cholesterol content were observed. Conclusion: Taken together, our results suggest that metformin and CaD could protect against the onset of HFFr diet-induced NAFLD in an insulin and AMPK-independent manner, without any marked additional benefits of their combination

Diatom-guided bone healing via a hybrid natural scaffold

Bone tissue engineering (BTE) involves the design of three-dimensional (3D) scaffolds that aim to address current challenges of bone defect healing, such as limited donor availability, disease transmission risks, and the necessity for multiple invasive surgeries. Scaffolds can mimic natural bone structure to accelerate the mechanisms involved in the healing process. Herein, a crosslinked combination of biopolymers, including gelatin (GEL), chitosan (CS), and hyaluronic acid (HA), loaded with diatom (Di) and β-sitosterol (BS), is used to produce GCH-Di-S scaffold by freeze-drying method. The GCH scaffold possesses a uniform structure, is biodegradable and biocompatible, and exhibits high porosity and interconnected pores, all required for effective bone repair. The incorporation of Di within the scaffold contributes to the adjustment of porosity and degradation, as well as effectively enhancing the mechanical property and biomineralization. In vivo studies have confirmed the safety of the scaffold and its potential to stimulate the creation of new bone tissue. This is achieved by providing an osteoconductive platform for cell attachment, prompting calcification, and augmenting the proliferation of osteoblasts, which further contributes to angiogenesis and anti-inflammatory effects of BS