Search

Recent advances in the field of skin patches have promoted the development of wearable and implantable bioelectronics for long-term, continuous healthcare management and targeted therapy. However, the design of electronic skin (e-skin) patches with stretchable components is still challenging and requires an in-depth understanding of the skin-attachable substrate layer, functional biomaterials and advanced self-powered electronics. In this comprehensive review, we present the evolution of skin patches from functional nanostructured materials to multi-functional and stimuli-responsive patches towards flexible substrates and emerging biomaterials for e-skin patches, including the material selection, structure design and promising applications. Stretchable sensors and self-powered e-skin patches are also discussed, ranging from electrical stimulation for clinical procedures to continuous health monitoring and integrated systems for comprehensive healthcare management. Moreover, an integrated energy harvester with bioelectronics enables the fabrication of self-powered electronic skin patches, which can effectively solve the energy supply and overcome the drawbacks induced by bulky battery-driven devices. However, to realize the full potential offered by these advancements, several challenges must be addressed for next-generation e-skin patches. Finally, future opportunities and positive outlooks are presented on the future directions of bioelectronics. It is believed that innovative material design, structure engineering, and in-depth study of fundamental principles can foster the rapid evolution of electronic skin patches, and eventually enable self-powered close-looped bioelectronic systems to benefit mankind.

Adhesive and stretchable nanofibrous hydrogels have attracted extensive attraction in wound dressings, especially for joint wound treatment. However, adhesive hydrogels tend to display poor stretchable behavior. It is still a significant challenge to integrate excellent adhesiveness and stretchability in a nanofibrous hydrogel. Herein, a highly adhesive, stretchable, and breathable nanofibrous hydrogel was developed via an in situ hybrid cross-linking strategy of electrospun nanofibers comprising dopamine (DA) and gelatin methacryloyl (GelMA). Benefiting from the balance of cohesion and adhesion based on photocross-linking of methacryloyl (MA) groups in GelMA and the chemical/physical reaction between GelMA and DA, the nanofibrous hydrogels exhibited tunable adhesive and mechanical properties through varying MA substitution degrees of GelMA. The optimized GelMA60-DA exhibited 2.0 times larger tensile strength (2.4 MPa) with an elongation of about 200%, 2.3 times greater adhesive strength (9.1 kPa) on porcine skin, and 3.1 times higher water vapor transmission rate (10.9 kg m -2 d -1 ) compared with gelatin nanofibrous hydrogels. In parallel, the GelMA60-DA nanofibrous hydrogels could facilitate cell growth and accelerate wound healing. This work presented a type of breathable nanofibrous hydrogels with excellent adhesive and stretchable capacities, showing great promise as wound dressings.

The use of injectable biomaterials for cell delivery is a rapidly expanding field which may revolutionize the medical treatments by making them less invasive. However, creating desirable cell carriers poses significant challenges to the clinical implementation of cell-based therapeutics. At the same time, no method has been developed to produce injectable microscaffolds (MSs) from electrospun materials. Here the fabrication of injectable electrospun nanofibers is reported on, which retain their fibrous structure to mimic the extracellular matrix. The laser-assisted micro-scaffold fabrication has produced tens of thousands of MSs in a short time. An efficient attachment of cells to the surface and their proliferation is observed, creating cell-populated MSs. The cytocompatibility assays proved their biocompatibility, safety, and potential as cell carriers. Ex vivo results with the use of bone and cartilage tissues proved that NaOH hydrolyzed and chitosan functionalized MSs are compatible with living tissues and readily populated with cells. Injectability studies of MSs showed a high injectability rate, while at the same time, the force needed to eject the load is no higher than 25 N. In the future, the produced MSs may be studied more in-depth as cell carriers in minimally invasive cell therapies and 3D bioprinting applications., (© 2021 Wiley-VCH GmbH.)

In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA-based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists' enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology-assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in-depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology-mediated RNA therapies are discussed., Competing Interests: The authors declare no conflict of interest., (© 2021 Wiley‐VCH GmbH.)

The spread of antimicrobial resistance requires the development of novel strategies to combat superbugs. Bacteriolytic enzymes (enzybiotics) that selectively eliminate pathogenic bacteria, including resistant strains and biofilms, are attractive alternatives to antibiotics, also as a component of a new generation of antimicrobial wound dressings. Auresine Plus is a novel, engineered enzybiotic effective against Staphylococcus aureus -one of the most common pathogenic bacteria, found in infected wounds with a very high prevalence of antibiotic resistance. We took advantage of its potent lytic activity, selectivity, and safety to prepare a set of biodegradable PLGA/chitosan fibers generated by electrospinning. Our aim was to produce antimicrobial nonwovens to deliver enzybiotics directly to the infected wound and better control its release and activity. Three different methods of enzyme immobilization were tested: physical adsorption on the previously hydrolyzed surface, and covalent bonding formation using N -hydroxysuccinimide/ N -(3-Dimethylaminopropyl)- N '-ethylcarbodiimide (NHS/EDC) or glutaraldehyde (GA). The supramolecular structure and functional properties analysis revealed that the selected methods resulted in significant development of nanofibers surface topography resulting in an efficient enzybiotic attachment. Both physically adsorbed and covalently bound enzymes (by NHS/EDC method) exhibited prominent antibacterial activity. Here, we present the extensive comparison between methods for the effective attachment of the enzybiotic to the electrospun nonwovens to generate biomaterials effective against antibiotic-resistant strains. Our intention was to present a comprehensive proof-of-concept study for future antimicrobial wound dressing development.

The poor intrinsic mechanical properties of chitosan hydrogels have greatly hindered their practical applications. Inspired by nature, we proposed a strategy to enhance the mechanical properties of chitosan hydrogels by construction of a nanofibrous and cellular architecture in the hydrogel without toxic chemical crosslinking. To this end, electrospun nanofibers including cellulose acetate, polyacrylonitrile, and SiO 2 nanofibers were introduced into chitosan hydrogels by homogenous dispersion and lyophilization. With the addition of 30% cellulose acetate nanofibers, the cellular structure could be maintained even in water without crosslinking, and integration of 60% of the nanofibers could guarantee the free-standing structure of the chitosan hydrogel with a low solid content of 1%. Moreover, the SiO 2 nanofiber-reinforced chitosan (SiO 2 NF/CS) three-dimensional (3D) matrices exhibit complete shape recovery from 80% compressive strain and excellent injectability. The cellular architecture and nanofibrous structure in the SiO 2 NF/CS matrices are beneficial for human mesenchymal stem cell adhesion and stretching. Furthermore, the SiO 2 NF/CS matrices can also act as powerful vehicles for drug delivery. As an example, bone morphogenetic protein 2 could be immobilized on SiO 2 NF/CS matrices to induce osteogenic differentiation. Together, the electrospun nanofiber-reinforced 3D chitosan matrices exhibited improved mechanical properties and enhanced biofunctionality, showing great potential in tissue engineering., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The recent progress in bioengineering has created great interest in the dynamics and manipulation of long, deformable macromolecules interacting with fluid flow. We report experimental data on the cross-flow migration, bending, and buckling of extremely deformable hydrogel nanofilaments conveyed by an oscillatory flow into a microchannel. The changes in migration velocity and filament orientation are related to the flow velocity and the filament's initial position, deformation, and length. The observed migration dynamics of hydrogel filaments qualitatively confirms the validity of the previously developed worm-like bead-chain hydrodynamic model. The experimental data collected may help to verify the role of hydrodynamic interactions in molecular simulations of long molecular chains dynamics.

An excessive glutamate level can result in excitotoxic damage and death of central nervous system (CNS) cells, and is involved in the pathogenesis of many CNS diseases. It may also be related to a failure of the blood-spinal cord barrier (BSCB). This study was aimed at examining the effects of extended administration of monosodium glutamate on the BSCB and spinal cord cells in adult male Wistar rats. The glutamate was delivered by subarachnoidal application of glutamate-carrying electrospun nanofiber mat dressing at the lumbar enlargement level. Half of the rats with the glutamate-loaded mat application were treated systemically with the histone deacetylase inhibitor valproic acid. A group of intact rats and a rat group with subarachnoidal application of an 'empty' (i.e., carrying no glutamate) nanofiber mat dressing served as controls. All the rats were euthanized three weeks later and lumbar fragments of their spinal cords were harvested for histological, immunohistochemical and ultrastructural studies. The samples from controls revealed normal parenchyma and BSCB morphology, whereas those from rats with the glutamate-loaded nanofiber mat dressing showed many intraparenchymal microhemorrhages of variable sizes. The capillaries in the vicinity of the glutamate-carrying dressing (in the meninges and white matter alike) were edematous and leaky, and their endothelial cells showed degenerative changes: extensive swelling, enhanced vacuo-lization and the presence of vascular intraluminal projections. However, endothelial tight junctions were generally well preserved. Some endothelial cells were dying by necrosis or apoptosis. The adjacent parenchyma showed astrogliosis with astrocytic hypertrophy and swelling of perivascular astrocytic feet. Neurons in the parenchyma revealed multiple symptoms of degeneration, including, inter alia, perikaryal, dendritic and axonal swelling, and destruction of organelles. All the damage symptoms were slightly less severe in the rats given valproic acid treatment, and were absent from both the intact rats and the rats with 'empty' nanofiber mat dressing. These results demonstrate that glutamate-loaded nanofiber mat dressing can locally create glutamate levels capable of damaging BSCB and that the resulting damage can be mitigated with concurrent systemic valproate treatment.

Recent biomedical hydrogels applications require the development of nanostructures with controlled diameter and adjustable mechanical properties. Here we present a technique for the production of flexible nanofilaments to be used as drug carriers or in microfluidics, with deformability and elasticity resembling those of long DNA chains. The fabrication method is based on the core-shell electrospinning technique with core solution polymerisation post electrospinning. Produced from the nanofibers highly deformable hydrogel nanofilaments are characterised by their Brownian motion and bending dynamics. The evaluated mechanical properties are compared with AFM nanoindentation tests.

Drug delivery systems based on nanofibrous mats appear to be a promising healing practice for preventing brain neurodegeneration after surgery. One of the problems encountered during planning and constructing optimal delivery system based on nanofibrous mats is the estimation of parameters crucial for predicting drug release dynamics. This study describes our experimental setup allowing for spatial and temporary evaluation of drug release from nanofibrous polymers to obtain data necessary to validate appropriate numerical models. We applied laser light sheet method to illuminate released fluorescent drug analog and CCD camera for imaging selected cross-section of the investigated volume. Transparent hydrogel was used as a brain tissue phantom. The proposed setup allows for continuous observation of drug analog (fluorescent dye) diffusion for time span of several weeks. Images captured at selected time intervals were processed to determine concentration profiles and drug release kinetics. We used presented method to evaluate drug release from several polymers to validate numerical model used for optimizing nanofiber system for neuroprotective dressing., (© 2014 Wiley Periodicals, Inc.)

The purpose of this study was to compare: a new five-layered poly (L-lactide-co-caprolactone) (PLC) membrane and small intestinal submucosa (SIS) as a control in rat urinary bladder wall regeneration. The five-layered poly (L-lactide-co-caprolactone) membrane was prepared by an electrospinning process. Adipose tissue was harvested from five 8-week old male Wistar rats. Adipose derived stem cells (ADSCs) were seeded in a density of 3×10(6) cells/cm2 onto PLC membrane and SIS scaffolds, and cultured for 5-7 days in the stem cell culture medium. Twenty male Wistar rats were randomly divided into five equal groups. Augmentation cystoplasty was performed in a previously created dome defect. Groups: (I) PLC+ 3×10(6)ADSCs; (II) SIS+ 3×10(6)ADSCs; (III) PLC; (IV) SIS; (V) control. Cystography was performed after three months. The reconstructed urinary bladders were evaluated in H&E and Masson's trichrome staining. Regeneration of all components of the normal urinary bladder wall was observed in bladders augmented with cell-seeded SIS matrices. The urinary bladders augmented with SIS matrices without cells showed fibrosis and graft contraction. Bladder augmentation with the PLC membrane led to numerous undesirable events including: bladder wall perforation, fistula or diverticula formation, and incorporation of the reconstructed wall into the bladder lumen. The new five-layered poly (L-lactide-co-caprolactone) membrane possesses poorer potential for regenerating the urinary bladder wall compared with SIS scaffold.

Traumatic/surgical brain injury can initiate a cascade of pathological changes that result, in the long run, in severe damage of brain parenchyma and encephalopathy. Excessive scarring can also interfere with brain function and the glial scar formed may hamper the restoration of damaged brain neural pathways. In this preliminary study we aimed to investigate the effect of dressing with an L-lactide-caprolactone copolymer nanofiber net on brain wound healing and the fate of the formed glial scar. Our rat model of surgical brain injury (SBI) of the fronto-temporal region of the sensorimotor cortex imitates well the respective human neurosurgery situation. Brains derived from SBI rats with net-undressed wound showed massive neurodegeneration, entry of systemic inflammatory cells into the brain parenchyma and the astrogliosis due to massive glial scar formation. Dressing of the wound with the nanofiber net delayed and reduced the destructive phenomena. We observed also a reduction in the scar thickness. The observed modification of local inflammation and cicatrization suggest that nanofiber nets could be useful in human neurosurgery.

(Sub)chronic local drug application is clearly superior to systemic administration, but may be associated with substantial obstacles, particularly regarding the applications to highly sensitive central nervous system (CNS) structures that are shielded from the outer environment by the blood-brain barrier. Violation of the integrity of the barrier and CNS tissues by a permanently implanted probe or cannula meant for prolonged administration of drugs into specific CNS structures can be a severe confounding factor because of the resulting inflammatory reactions. In this study, we tested the utility of a novel way for (sub)chronic local delivery of highly active (i.e., used in very low amounts) drugs to the rat spinal cord employing a non-woven nanofiber mat dressing. To this end, we compared the morphology and motoneuron ( + ) counts in spinal cord cervical and lumbar segments between rats with glutamate-loaded nanofiber mats applied to the lumbar enlargement and rats with analogical implants carrying no glutamate. Half of the rats with glutamate-loaded implants were given daily valproate treatment to test its potential for counteracting the detrimental effects of glutamate excess. The mats were prepared in-house by electrospinning of an emulsion made of a solution of the biocompatible and biodegradable poly(L-lactide-co-caprolactone) polymer in a mixture of organic solvents, an aqueous phase with or without monosodium glutamate, and sodium dodecyl sulfate as an emulsifier; the final glutamate content was 1.4 µg/mg of the mat. Three weeks after mat implantation there was no inflammation or considerable damage of the spinal cord motoneuron population in the rats with the subarachnoid dressing of a glutamate-free mat, whereas the spinal cords of the rats with glutamate-loaded nanofiber mats showed clear symptoms of excitotoxic damage and a substantial increase in dying/damaged motoneuron numbers in both segments studied. The rats given systemic valproate treatment showed significantly lower percentages of damaged/dying motoneurons in their lumbar enlargements. These results demonstrate the capacity of nanofiber mats for generation of neurotoxic glutamate in the rat CNS. However, the tested nanofiber mats need further improvements aimed at extending the period of effective drug release and rendering the release more steady.