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Near-field electrospinning (NFES) has recently gained considerable interest in fabricating tissue engineering scaffolds. This technique combines the advantages of both 3D printing and electrospinning. It allows for the production of fibers with smaller resolution and the ability to make regular structures with suitable pores. In this study, a microfibrous composite scaffold of polycaprolactone (PCL)/hydroxyapatite (HA) was prepared by NFES in the first step. The microfibrous scaffold had a fiber spacing of 414.674 ± 24.9 μm with an average fiber diameter of 94.695 ± 16.149 μm. However, due to the large fiber spacing, the surface area was insufficient for cell adhesion. Therefore, the hybrid scaffold was prepared by adding aligned and random electrospun poly (L-lactic acid) (PLLA) nanofibers to the microfibrous scaffold. Cellular studies showed that cell adhesion to the hybrid scaffold increased by 334 % compared to the microfibrous scaffold. These nanofibers also exhibited piezoelectric properties, which helped stimulate bone regeneration. Aligned nanofibers in the hybrid scaffold enhanced alkaline phosphatase activity and the intensity of alizarin red staining 1.5 and 1.6 times, respectively, compared to the microfibrous scaffold. Furthermore, the elastic modulus and ultimate tensile strength increased by 268 % and 130 %, respectively, by adding aligned nanofibers to the microfibrous scaffold. Therefore, the hybrid microfibrous composite scaffold of PCL/HA containing aligned electrospun PLLA nanofibers with improved properties showed the potential for bone regeneration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

3D (Bio)printing is a highly effective method for fabricating tissue engineering scaffolds, renowned for their exceptional precision and control. Artificial intelligence (AI) has become a crucial technology in this field, capable of learning and replicating complex patterns that surpass human capabilities. However, the integration of AI in tissue engineering is often hampered by the lack of comprehensive and reliable data. This study addresses these challenges by providing one of the most extensive datasets on 3D-printed scaffolds. It provides the most comprehensive open-source dataset and employs various AI techniques, from unsupervised to supervised learning. This dataset includes detailed information on 1171 scaffolds, featuring a variety of biomaterials and concentrations-including 60 biomaterials such as natural and synthesized biomaterials, crosslinkers, enzymes, etc.-along with 49 cell lines, cell densities, and different printing conditions. We used over 40 machine learning and deep learning algorithms, tuning their hyperparameters to reveal hidden patterns and predict cell response, printability, and scaffold quality. The clustering analysis using KMeans identified five distinct ones. In classification tasks, algorithms such as XGBoost, Gradient Boosting, Extra Trees Classifier, Random Forest Classifier, and LightGBM demonstrated superior performance, achieving higher accuracy and F1 scores. A fully connected neural network with six hidden layers from scratch was developed, precisely tuning its hyperparameters for accurate predictions. The developed dataset and the associated code are publicly available onhttps://github.com/saeedrafieyan/MLATEto promote future research., (© 2024 IOP Publishing Ltd.)

Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Despite its advantages, electrospinning has limited effectiveness in 3D scaffolding due to the high density of fibers it produces. In this research, a novel electrospinning collector was developed to overcome this constraint. An aqueous suspension containing chitosan/polyvinyl alcohol nanofibers was prepared employing a unique falling film collector. Suspension molding by freeze-drying resulted in a 3D nanofibrous scaffold (3D-NF). The mineralized scaffold was obtained by brushite deposition on 3D-NF using wet chemical mineralization by new sodium tripolyphosphate and calcium chloride dihydrate precursors. The 3D-NF was optimized and compared with the conventional electrospun 2D nanofibrous scaffold (2D-NF) and the 3D freeze-dried scaffold (3D-FD). Both minor fibrous and major freeze-dried pore shapes were present in 3D-NFs with sizes of 16.11-24.32 μm and 97.64-234.41 μm, respectively. The scaffolds' porosity increased by 53 % to 73 % compared to 2D-NFs. Besides thermal stability, mineralization improved the 3D-NF's ultimate strength and elastic modulus by 2.2 and 4.7 times, respectively. In vitro cell studies using rat bone marrow mesenchymal cells confirmed cell infiltration up to 290 μm and scaffold biocompatibility. The 3D-NFs given nanofibers and brushite inclusion exhibited considerable osteoinductivity. Therefore, falling film collectors can potentially be applied to prepare 3D-NFs from electrospinning without post-processing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aqueous core-shell structures can serve as an efficient approach that allows cells to generate 3D spheroids with in vivo -like cell-to-cell contacts. Here, a novel strategy for fabricating liquid-core-shell capsules is proposed by inverse gelation of alginate (ALG) and layer-by-layer (LbL) coating. We hypothesized that the unique properties of polyethylenimine (PEI) could be utilized to overcome the low structural stability and the limited cell recognition motifs of ALG. In the next step, alginate dialdehyde (ADA) enabled the Schiff-base reaction with free amine groups of PEI to reduce its possible toxic effects. Scanning electron microscopy and light microscopy images proved the formation of spherical hollow capsules with outer diameters of 3.0 ± 0.1 mm for ALG, 3.2 ± 0.1 mm for ALG/PEI, and 4.0 ± 0.2 mm for ALG/PEI/ADA capsules. The effective modulus increased by 3-fold and 5-fold when comparing ALG/PEI/ADA and ALG/PEI to ALG capsules, respectively. Moreover, PEI-coated capsules showed potential antibacterial properties against both Staphylococcus aureus and Escherichia coli , with an apparent inhibition zone. The cell viability results showed that all capsules were cytocompatible (above 75.5%). Cells could proliferate and form spheroids when encapsulated within the ALG/PEI/ADA capsules. Monitoring the spheroid thickness over 5 days of incubation indicated an increasing trend from 39.50 μm after 1 day to 66.86 μm after 5 days. The proposed encapsulation protocol represents a new in vitro platform for developing 3D cell cultivation and can be adapted to fulfill the requirements of various biomedical applications.

Genipin-cross-linked silk fibroin (SF) hydrogel is considered to be biocompatible and mechanically robust. However, its use remains a challenge for in situ forming applications due to its prolonged gelation process. In our attempt to facilitate the in situ fabrication of a genipin-mediated SF hydrogel, alginate dialdehyde (ADA) was utilized as a reinforcement template. Here, SF/ADA-based hydrogels with different compositions were synthesized covalently and ionically. Incorporating ADA into the SF hydrogel increased pore size (44.66-174.66 μm), porosity (61.59-80.40%), and the equilibrium swelling degree (7.60-30.17). Moreover, a wide range of storage modulus and compressive modulus were obtained by adjusting the proportions of SF and ADA networks within the hydrogel. The in vitro cell analysis using preosteoblast cells (MC3T3-E1) demonstrated the cytocompatibility of all hydrogels. Overall, the covalently and ionically cross-linked SF/ADA hydrogel represents a promising solution for in situ forming hydrogels for applications in tissue regeneration.

Pattern recognition receptors (PRRs) induce host defense but can also induce exacerbated inflammatory responses. This raises the question of whether other mechanisms are also involved in early host defense. Using transcriptome analysis of disrupted transcripts in herpes simplex virus (HSV)-infected cells, we find that HSV infection disrupts the hypoxia-inducible factor (HIF) transcription network in neurons and epithelial cells. Importantly, HIF activation leads to control of HSV replication. Mechanistically, HIF activation induces autophagy, which is essential for antiviral activity. HSV-2 infection in vivo leads to hypoxia in CNS neurons, and mice with neuron-specific HIF1/2α deficiency exhibit elevated viral load and augmented PRR signaling and inflammatory gene expression in the CNS after HSV-2 infection. Data from human stem cell-derived neuron and microglia cultures show that HIF also exerts antiviral and inflammation-restricting activity in human CNS cells. Collectively, the HIF transcription factor system senses virus-induced hypoxic stress to induce cell-intrinsic antiviral responses and limit inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)