Current treatment strategies for Glioblastoma (GBM)-including surgery, radiotherapy, and chemotherapy with oral administration of temozolomide (TMZ)-still lead to poor survival rates, making the development of more effective therapeutic methods an urgent need. This study presents a new approach for the treatment of GBM patients using a 3D-printed hydrogel-based mesh (GlioMesh), loaded with TMZ-releasing microparticles, that is capable of delivering TMZ over several weeks at the tumor site. Given the challenges associated with loading the amphiphilic TMZ in polymeric substrates, a novel encapsulation strategy is developed using an oil-in-oil emulsion method that improves the encapsulation efficiencies of TMZ in poly(lactic-co-glycolic acid) (PLGA) from <7% to about 61%. The cytotoxic effects of GlioMesh on GBM cells are evaluated in vitro by investigating the resultant levels of DNA break, autophagic activity, and mitochondrial damage. It is shown that GlioMesh produces significantly higher susceptibility to the drug in comparison with free TMZ by maintaining the level of autophagic activity and inducing larger degrees of mitochondrial damage. Sustained delivery of TMZ holds promise for suppressing chemoresistance to TMZ that is normally developed in GBM cells in systemic administration of the drug due to the induction of autophagy.
Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with Escherichia coli to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to Escherichia coli, the level of IL-1β and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1β and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing.
An effective treatment of human diseases using regenerative medicine and cell therapy approaches requires a large number of cells. Cultivation of cells on microcarriers is a promising approach due to the high surface‐to‐volume ratios that these microcarriers offer. Here, multifunctional temperature‐responsive microcarriers (cytoGel) made of an interpenetrating hydrogel network composed of poly(N‐isopropylacrylamide) (PNIPAM), poly(ethylene glycol) diacrylate (PEGDA), and gelatin methacryloyl (GelMA) are developed. A flow‐focusing microfluidic chip is used to produce microcarriers with diameters in the range of 100–300 μm and uniform size distribution (polydispersity index of ≈0.08). The mechanical properties and cells adhesion properties of cytoGel are adjusted by changing the composition hydrogel composition. Notably, GelMA regulates the temperature response and enhances microcarrier stiffness. Human‐derived glioma cells (U87) are grown on cytoGel in static and dynamic culture conditions with cell viabilities greater than 90%. Enzyme‐free cell detachment is achieved at room temperature with up to 70% detachment efficiency. Controlled release of bioactive molecules from cytoGel is accomplished for over a week to showcase the potential use of microcarriers for localized delivery of growth factors to cell surfaces. These microcarriers hold great promise for the efficient expansion of cells for the industrial‐scale culture of therapeutic cells.
Following the emergence of severe acute respiratory syndrome (SARS) in 2002 and the Middle East respiratory syndrome (MERS) in 2012, the world is now combating a third large‐scale outbreak caused by a coronavirus, the coronavirus disease 2019 (COVID‐19). After the rapid spread of SARS‐coronavirus (CoV)‐2 (the virus causing COVID‐19) from its origin in China, the World Health Organization (WHO) declared a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. From the beginning of the COVID‐19 pandemic, a significant number of studies have been conducted to better understand the biology and pathogenesis of the novel coronavirus, and to aid in developing effective treatment regimens, therapeutics, and vaccines. This review focuses on the recent advancements in the rapidly evolving areas of clinical care and management of COVID‐19. The emerging strategies for the diagnosis and treatment of this disease are explored, and the development of effective vaccines is reviewed.
In article 1900113 Mohsen Akbari and co‐workers develop a hydrogel‐based mesh containing temozolomide‐loaded poly(lactic‐co‐glycolic acid) microspheres with high encapsulation efficiency (GlioMesh) that can release anticancer drugs directly at a tumor site. GlioMesh can conform to the irregular structure of brain tissue because of its flexibility and release drugs for up to two months.
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