This study was designed to develop a drug delivery system based on poly(Nisopropylacrylamide) (pNIPAM) hydrogel and a suitable solvent to enhance solubility and local release of curcumin. pNIPAM hydrogel was synthesized by radical polymerization. The chemical, mechanical and physical properties and biocompatibility of pNIPAM hydrogel were investigated as an implantable and rechargeable drug reservoir. Curcumin was loaded within pNIPAM hydrogel during swelling by using two different solvents; methanol, an organic solvent, and low molecular weight polyethylene glycol (PEG200), a polymeric solvent. The results of drug solubility showed that using PEG200 can increase curcumin solubility more than commonly used organic solvents such as methanol. Also, the release profile of drug-loaded hydrogels demonstrated that PEG200 has a superior effect on the cumulative amount of released curcumin (33.163 ± 0.319 μg/ml) compared to methanol (8.765 ± 0.544 μg/ml) during 1 week. Based on our results, curcumin-loaded hydrogels did not show any cytotoxicity, and pNIPAM/PEG combination represented an antibacterial effect within 12 hours. Accordingly, it can be concluded that pNIPAM hydrogel in combination with low molecular weight PEG200 could be used as an efficient drug delivery system to preserve and provide sustained release of curcumin as a hydrophobic drug. K E Y W O R D S applications, biomaterials, drug delivery systems 1 | INTRODUCTION Curcumin, a natural organic compound, has been shown to have anti-inflammatory, antioxidant, anticarcinogenic, and antiangiogenic activity. 1 It is a lipophilic compound

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Hydrogels have been used as promising biomaterials for regeneration and control of pathophysiological events after traumatic spinal cord injuries (TSCI). However, no systematic comparison was conducted to show the effect of hydrogels on pathophysiological events. This study was designed to address this issue and evaluate the regenerative potential of hydrogels after TSCI. From 2857 records found in MEDLINE and EMBASE databases (April 23, 2021), 49 articles were included based on our inclusion/exclusion criteria. All studies discussing the effect of hydrogels on at least one of the main pathophysiological events after TSCI, including inflammation, axon growth, remyelination, glial scar formation, cavity size, and locomotor functional recovery were included. For statistical analysis, we used mean difference with 95% confidence intervals for locomotor functional recovery. The results showed that both natural and synthetic hydrogels could reduce the inflammatory response, hinder glial scar formation, and promote axon growth and vascularization. Also, the meta‐analysis of the BBB score showed that using the hydrogels can lead to locomotor functional recovery. It was found that hydrogels are more efficient when used in transection and hemisection injuries (SMD: 1.89; 95% CI: 1.26, 2.52; P < .00001) compared to other injury models. The pre‐formed implanted hydrogels (SMD: 1.79; 95% CI: 1.24, 2.34; P < .00001) found to be more effective compared to injection (SMD: 1.58; 95% CI: 0.64, 2.52; P = 0.0009). In conclusion, based on the available evidence, it was concluded that hydrogel composition as well as implantation method are dominant factors affecting tissue regeneration after TSCI and should be chosen according to the injury model in animal studies.

The loss of neurons is one of the most irreversible phenomena in traumatic injuries to the central nervous system (CNS). One of the recent approaches to replace the lost neurons is delivering stem cells to the lesion area and differentiating them using biodegradable scaffolds. Alginate has been known as an efficient hydrogel for this target. However, its bioactivity needs to be improved to promote cell adhesion/differentiation. In this study, alginate hydrogel was synthesized and optimized regarding mechanical properties of the CNS, and its bioactivity was improved using Schwann cell-and fibroblast-derived extracellular matrix (ECM). The results of immunostaining showed higher differentiation efficacy on ECM-modified hydrogels than controls. Although secreted protein content by fibroblast was 12.01 ± 2.09 folds higher than Schwann cells, no significant difference was observed between the differentiation potential of ECM-modified hydrogels. Accordingly, both ECM-modified hydrogels can be an appropriate scaffold to promote differentiation toward neuron-like cells and, subsequently, nerve regeneration.

Time-lapse light microscopy combined with in vitro neuronal cultures has provided a significant contribution to the field of Developmental Neuroscience. The establishment of the neuronal polarity, i.e., formation of axons and dendrites, key structures responsible for inter-neuronal signaling, was described in 1988 by Dotti, Sullivan and Banker in a milestone paper that continues to be cited 30 years later. In the following decades, numerous fluorescently labeled tags and dyes were developed for live cell imaging, providing tremendous advancements in terms of resolution, acquisition speed and the ability to track specific cell structures. However, long-term recordings with fluorescence-based approaches remain challenging because of light-induced phototoxicity and/or interference of tags with cell physiology (e.g., perturbed cytoskeletal dynamics) resulting in compromised cell viability leading to cell death. Therefore, a label-free approach remains the most desirable method in long-term imaging of living neurons. In this paper we will focus on label-free high-resolution methods that can be successfully used over a prolonged period. We propose novel tools such as scanning ion conductance microscopy (SICM) or digital holography microscopy (DHM) that could provide new insights into live cell dynamics during neuronal development and regeneration after injury.