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Abstract Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m−1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural‐tissue‐like low conductivity (0.02–0.1 S m−1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m−1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic‐transcription‐factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural‐tissue‐like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

Highlights Nanozyme-based approaches to produce therapeutic hydrogels. Enzymatic mechanisms and multifunctional roles of nanozyme-engineered hydrogels for skin therapy. Therapeutic actions of nanozyme-engineered hydrogels in inflamed skin tissues. Mechanical and immunological aspects of skin therapy guided by nanozyme-engineered hydrogels. Promising directions and challenges of nanozyme-inspired hydrogel platforms.

Bone defects in patients entail the microenvironment that needs to boost the functions of stem cells (e.g., proliferation, migration, and differentiation) while alleviating severe inflammation induced by high oxidative stress. Biomaterials can help to shift the microenvironment by regulating these multiple events. Here we report multifunctional composite hydrogels composed of photo-responsive Gelatin Methacryloyl (GelMA) and dendrimer (G3)-functionalized nanoceria (G3@nCe). Incorporation of G3@nCe into GelMA could enhance the mechanical properties of hydrogels and their enzymatic ability to clear reactive oxygen species (ROS). The G3@nCe/GelMA hydrogels supported the focal adhesion of mesenchymal stem cells (MSCs) and further increased their proliferation and migration ability (vs. pristine GelMA and nCe/GelMA). Moreover, the osteogenic differentiation of MSCs was significantly stimulated upon the G3@nCe/GelMA hydrogels. Importantly, the capacity of G3@nCe/GelMA hydrogels to scavenge extracellular ROS enabled MSCs to survive against H2O2-induced high oxidative stress. Transcriptome analysis by RNA sequencing identified the genes upregulated and the signalling pathways activated by G3@nCe/GelMA that are associated with cell growth, migration, osteogenesis, and ROS-metabolic process. When implanted subcutaneously, the hydrogels exhibited excellent tissue integration with a sign of material degradation while the inflammatory response was minimal. Furthermore, G3@nCe/GelMA hydrogels demonstrated effective bone regeneration capacity in a rat critical-sized bone defect model, possibly due to an orchestrated capacity of enhancing cell proliferation, motility and osteogenesis while alleviating oxidative stress.

Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells. Among others, methacrylated gelatin (GelMA) has become a representative hydrogel formulation, finding various biomedical applications. Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials, aiming to provide enhanced physicochemical and biological properties to GelMA. The benefits of this approach are multiple: i) reinforcing mechanical properties, ii) modulating viscoelastic property to allow 3D printability of bio-inks, iii) rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues (e.g., muscle, nerve), iv) providing stimuli-responsiveness to actively deliver therapeutic molecules, and v) endowing therapeutic capacity in tissue repair process (e.g., antioxidant effects). The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues (bone, skin, cardiac, and nerve) that are rarely observable with GelMA. Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics. The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.

Bioactive phosphate glasses incorporated with Zn2+ (predicted to be useful for bone regeneration applications) were synthesized. Characterization of the bioglasses were done using XRD, FTIR, SEM, and EDS techniques, both prior to and after soaking in simulated body fluid (SBF) solution. The bioactive performance of samples was evaluated by incubated in SBF for different days by means of the pH measuring and comparing the results of XRD and SEM studies. The obtained results show the formation of hydroxyapatite (HAP) layer on the surface of as-developed bioactive glasses. The degradation of the samples evaluated by weight loss and pH of the remnant solution measured as functions of ZnO concentration and immersion time revealed the enhanced formation of HAP layer on the sample surface. The results further indicated the rate of degradation can be monitored by tailoring the concentration of ZnO and immersion time. The studies were also extended to in vitro cytocompatibility and cell proliferation measurements on rMSC using CCK-8 for incubation periods of 24 h and 72 h. These studies have revealed the considerable levels of rMSC proliferation and improved viability within the limits of nontoxic levels. The measurements of antibacterial activity of ZnO-doped phosphate bioactive glasses against E. coli and S. aureus, carried out for 24 h and 48 h have confirmed their potential antibacterial activity. Finally, quantitative analysis of these results confirmed an enhanced in vitro biological and antibacterial activity of the samples due to the ZnO doping and subsequent controlled release of Zn2+ ions in the glass matrix.

Abstract A high specific capacity conducting reduced graphene oxide nanosulfur nanocomposite (RGOSNC) cathode is synthesized via deposition of nanosulfur on graphene oxide (GO) through the hydrothermal treatment in the presence of multifaceted ethylenediamine (EDA) for improving the performance of lithium‐sulfur battery (LiSB). The maximum utilization of active material (sulfur) is facilitated by the attachment of nanosulfur to GO via EDA, and further, optimum reduction of GO into conducting, porous and interconnected RGO is performed via hydrothermal treatment in the available solution having residual EDA. Therefore, GO is reduced in highly conducting RGO without the use of any external reducing agent; minimizing the chance of impurity in the synthesized RGOSNC. A three‐dimensional interconnected porous conducting architecture with nitrogen (heteroatom) doping in RGO of RGOSNC with conductivity ∼1.83 S/cm assists easy electron transportation through conducting RGO network and stabilizes intermediate polysulfide to prevent loss of active material during the electrochemical performance. The synthesized RGOSNC cathode material delivers high initial specific capacities 1448 and 1040 mAh/g at 0.1 and 0.5 C, respectively. Prepared LiSB maintains ∼741 mAh/g retention over 100 cycles at 0.5 C with excellent Coulombic efficiency (∼99%).

The dura mater, as the crucial outermost protective layer of the meninges, plays a vital role in safeguarding the underlying brain tissue. Neurosurgeons face significant challenges in dealing with trauma or large defects in the dura mater, as they must address the potential complications, such as wound infections, pseudomeningocele formation, cerebrospinal fluid leakage, and cerebral herniation. Therefore, the development of dural substitutes for repairing or reconstructing the damaged dura mater holds clinical significance. In this review we highlight the progress in the development of dural substitutes, encompassing autologous, allogeneic, and xenogeneic replacements, as well as the polymeric-based dural substitutes fabricated through various scaffolding techniques. In particular, we explore the development of composite materials that exhibit improved physical and biological properties for advanced dural substitutes. Furthermore, we address the challenges and prospects associated with developing clinically relevant alternatives to the dura mater.

Nanoparticle-based therapeutics delivery holds great promise for the treatment of intractable diseases. The high loading of drug molecules and their precise delivery to target sites are needed to gain optimal therapeutic functions of the nanoparticle delivery system. In this communication, we highlight, among other properties of nanoparticles (e.g. size, shape, surface chemistry, and degradation), the nanoscale topography, which has recently been shown to be an important parameter, ultimately determining drug loading, cell penetration, and body clearance. This nanotopographical aspect is considered to offer a new effective strategy to the development of nanoparticles for drug and gene delivery with enhanced therapeutic outcome.

An effort was made to analyze the spatial and temporal variability of rainfall and temperature in 13 districts of the Uttarakhand, India over the period of 102 years (1901–2002). The main focus was to examine the rainfall variability and its future response during wheat crop period (November-April). Mann–Kendall test and Sen's slope estimator test used to detect monotonic trend direction and magnitude of change over time on annual and seasonal basis. The Pettit-Mann–Whitney test applied to detect the change points over the century. Mean annual precipitation varied from 821 mm (in Haridwar) to 1244 mm (in Pithoragarh) whereas it was 75 mm (in Udham Singh Nagar) to 178 mm (in Pithoragarh) during wheat growing period. During the wheat crop period, annual precipitation decrease was noticed in Udham Singh Nagar (-37.1%) which was maximum. Maximum decrease in minimum and maximum temperature during wheat growing period and annual period was observed for Uttarkashi district which was -39.4%, -28% and -25.1%, -21.1%, respectively. Similarly, Champawat was second after Udham Singh Nagar having highest temperature in both the periods. The most affected year of change was 1978 and 1940 in annual precipitation and maximum, minimum temperature, but during wheat growing period it was observed in 1945 and 1978, respectively. Mann Kendal trend test shows decrease in precipitation for all the stations during wheat growing period and annual period. In case of annual minimum temperature, average change was 0.0040C, though during wheat crop period it was 0.009 0C /year.

Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mechanical compression and restoration. Among the possible therapies, tissue engineering of osteochondral tissues has shown considerable promise where multiple approaches of utilizing cells, scaffolds, and signaling molecules have been pursued. This review focuses particularly on the importance of scaffold design and its role in the success of osteochondral tissue engineering. Biphasic and gradient composition with proper pore configurations are the basic design consideration for scaffolds. Surface modification is an essential technique to improve the scaffold function associated with cell regulation or delivery of signaling molecules. The use of functional scaffolds with a controllable delivery strategy of multiple signaling molecules is also considered a promising therapeutic approach. In this review, we updated the recent advances in scaffolding approaches for osteochondral tissue engineering.

Magnetic nanofibrous scaffolds of poly(caprolactone) (PCL) incorporating magnetic nanoparticles (MNP) were produced, and their effects on physico-chemical, mechanical and biological properties were extensively addressed to find efficacy for bone regeneration purpose. MNPs 12 nm in diameter were citrated and evenly distributed in PCL solutions up to 20% and then were electrospun into nonwoven nanofibrous webs. Incorporation of MNPs greatly improved the hydrophilicity of the nanofibers. Tensile mechanical properties of the nanofibers (tensile strength, yield strength, elastic modulus and elongation) were significantly enhanced with the addition of MNPs up to 15%. In particular, the tensile strength increase was as high as ∼25 MPa at 15% MNPs vs. ∼10 MPa in pure PCL. PCL-MNP nanofibers exhibited magnetic behaviors, with a high saturation point and hysteresis loop area, which increased gradually with MNP content. The incorporation of MNPs substantially increased the degradation of the nanofibers, with a weight loss of ∼20% in pure PCL, ∼45% in 10% MNPs and ∼60% in 20% MNPs. Apatite forming ability of the nanofibers tested in vitro in simulated body fluid confirmed the substantial improvement gained by the addition of MNPs. Osteoblastic cells favored the MNPs-incorporated nanofibers with significantly improved initial cell adhesion and subsequent penetration through the nanofibers, compared to pure PCL. Alkaline phosphatase activity and expression of genes associated with bone (collagen I, osteopontin and bone sialoprotein) were significantly up-regulated in cells cultured on PCL-MNP nanofibers than those on pure PCL. PCL-MNP nanofibers subcutaneously implanted in rats exhibited minimal adverse tissue reactions, while inducing substantial neoblood vessel formation, which however, greatly limited in pure PCL. In vivo study in radial segmental defects also signified the bone regeneration ability of the PCL-MNP nanofibrous scaffolds. The magnetic, bone-bioactive, mechanical, cellular and tissue attributes of MNP-incorporated PCL nanofibers make them promising candidate scaffolds for bone regeneration.

Drug molecules with lack of specificity and solubility lead patients to take high doses of the drug to achieve sufficient therapeutic effects. This is a leading cause of adverse drug reactions, particularly for drugs with narrow therapeutic window or cytotoxic chemotherapeutics. To address these problems, there are various functional biocompatible drug carriers available in the market, which can deliver therapeutic agents to the target site in a controlled manner. Among the carriers developed thus far, mesoporous materials emerged as a promising candidate that can deliver a variety of drug molecules in a controllable and sustainable manner. In particular, mesoporous silica nanoparticles are widely used as a delivery reagent because silica possesses favourable chemical properties, thermal stability and biocompatibility. Currently, sol-gel-derived mesoporous silica nanoparticles in soft conditions are of main interest due to simplicity in production and modification and the capacity to maintain function of bioactive agents. The unique mesoporous structure of silica facilitates effective loading of drugs and their subsequent controlled release. The properties of mesopores, including pore size and porosity as well as the surface properties, can be altered depending on additives used to fabricate mesoporous silica nanoparticles. Active surface enables functionalisation to modify surface properties and link therapeutic molecules. The tuneable mesopore structure and modifiable surface of mesoporous silica nanoparticle allow incorporation of various classes of drug molecules and controlled delivery to the target sites. This review aims to present the state of knowledge of currently available drug delivery system and identify properties of an ideal drug carrier for specific application, focusing on mesoporous silica nanoparticles.