Neurological degeneration after neuroinflammation, such as that resulting from Alzheimer’s disease (AD), stroke, multiple sclerosis (MS), and post-traumatic brain injury (TBI), is typically associated with high mortality and morbidity and with permanent cognitive dysfunction, which places a heavy economic burden on families and society. Diagnosing and curing these diseases in their early stages remains a challenge for clinical investigation and treatment. Recent insight into the onset and progression of these diseases highlights the permeability of the blood–brain barrier (BBB). The primary factor that influences BBB structure and function is inflammation, especially the main cytokines including IL-1β, TNFα, and IL-6, the mechanism on the disruption of which are critical component of the aforementioned diseases. Surprisingly, the main cytokines from systematic inflammation can also induce as much worse as from neurological diseases or injuries do. In this review, we will therefore discuss the physiological structure of BBB, the main cytokines including IL-1β, TNFα, IL-6, and their mechanism on the disruption of BBB and recent research about the main cytokines from systematic inflammation inducing the disruption of BBB and cognitive impairment, and we will eventually discuss the need to prevent the disruption of BBB.

Significance: Wound dressings are frequently used for wound covering and healing. Ideal wound dressings should provide a moist environment for wounds and actively promote wound healing and skin recovery. The materials used as ideal wound dressings should possess specific properties, thus accelerating skin tissue regeneration process. Recent Advances: Bacterial cellulose (BC) is a natural polymer synthesized by some bacteria. As a kind of natural biopolymer, BC shows good biological activity, biodegradability, and biological adaptability. It has many unique physical, chemical, and biological properties, such as ultrafine nanofiber network, high crystallinity, high water absorption and retention capacity, and high tensile strength and elastic modulus. These excellent properties of BC have laid the foundation for its application as dressing in wound healing. Critical Issues: To optimize the biocompatibility and antimicrobial activity of BC, different methods including microbial fermentation, physical modification, chemical modification, and compound modification have been adopted to modify BC to ensure a better application in wound healing. BC-based wound dressings have been applied in infected wounds, acute traumatic injuries, burns, and diabetic wounds, showing remarkable therapeutic effects on promoting wound healing. Furthermore, there have been some commercial BC-based dressings and they have been utilized in clinical practice. Future Directions: Because of its excellent physicochemical characteristics and biological properties, BC shows high clinical value to be used as a wound dressing for skin tissue regeneration.

Uncontrollable hemorrhage leads to high mortality and thus effective bleeding control becomes increasingly important in the military field and civilian trauma arena. However, current hemostats not only present limitation when treating major bleeding, but also have various side effects. Here we report a self-expanding porous composites (CMCP) based on novel carboxymethyl cellulose (CMC) fibers and acetalized polyvinyl alcohol (PVA) for lethal hemorrhage control. The CMC fibers with uniform fibrous structure, high liquid absorption and procoagulant ability, are evenly interspersed inside the composite matrix. The obtained composites possess unique fiber-porous network, excellent absorption capacity, fast liquid-triggered self-expanding ability and robust fatigue resistance, and their physicochemical performance can be fine-tuned through varying the CMC content. In vitro tests show that the porous composite exhibits strong blood clotting ability, high adhesion to blood cells and protein, and the ability to activate platelet and the coagulation system. In vivo hemostatic evaluation further confirms that the CMCP presents high hemostatic efficacy and multiple hemostatic effects in swine femoral artery major hemorrhage model. Additionally, the CMCP will not fall off from the injury site, and is also easy to surgically remove from the wound cavity after the hemostasis. Importantly, results of CT tomography and 3D reconstruction indicate that CMCP can achieve shape adaptation to the surrounding tissues and the wound cavities with different depths and shapes, to accelerate hemostasis while protecting wound tissue and preventing infection.

Background: Hydrogels with tuneable mechanical properties are an attractive material platform for 3D bioprinting. Thus far, numerous studies have confirmed that the biophysical cues of hydrogels, such as stiffness, are known to have a profound impact on mesenchymal stem cell (MSC) differentiation; however, their differentiation potential within 3D-bioprinted hydrogels is not completely understood. Here, we propose a protocol for the exploration of how the stiffness of alginate–gelatin (Alg-Gel) composite hydrogels (the widely used bioink) affects the differentiation of MSCs in the presence or absence of differentiation inducing factors. Methods: Two types of Alg-Gel composite hydrogels (Young’s modulus: 50 kPa vs. 225 kPa) were bioprinted independently of porosity. Then, stiffness-induced biases towards adipogenic and osteogenic differentiation of the embedded MSCs were analysed by co-staining with alkaline phosphatase (ALP) and oil red O. The expression of specific markers at the gene level was detected after a 3-day culture. Results: Confocal microscopy indicated that all tested hydrogels supported MSC growth and viability during the culture period. Higher expression of adipogenic and osteogenic markers (ALP and lipoprotein lipase (LPL)) in stiffer 3D-bioprinted matrices demonstrated a more significant response of MSCs to stiffer hydrogels with respect to differentiation, which was more robust in differentiation-inducing medium. However, the LPL expression in stiffer 3D-bioprinted constructs was reduced at day 3 regardless of the presence of differentiation-inducing factors. Although MSCs embedded in softer hydrogels to some extent proceeded toward adipogenic and osteogenic lineages within a few days, their differentiation seemed to be slower and more limited. Interestingly, the hydrogel itself (without differentiation-inducing factors) exhibited a slight effect on whether MSCs differentiated towards an adipogenic or an osteogenic fate. Considering that the mechano-regulated protein Yes-associated protein (YAP) is involved in MSC fate decisions, we further found that inhibition of YAP significantly downregulated the expression of ALP and LPL in MSCs in stiffer constructs regardless of the induced growth factors present. Conclusions: These results demonstrate that the differentiation of MSCs in 3D-bioprinted matrices is dependent on hydrogel stiffness, which emphasizes the importance of biophysical cues as a determinant of cellular behaviour.

Neurological syndromes are observed in numerous patients who suffer burns, which add to the economic burden of societies and families. Recent studies have implied that blood–brain barrier (BBB) dysfunction is the key factor that induces these central nervous system (CNS) syndromes in peripheral traumatic disease, e.g., surgery and burns. However, the effect of burns on BBB and the underlying mechanism remains, largely, to be determined. The present study aimed to investigate the effect of burns on BBB and the potential of umbilical cord-derived mesenchymal stem cells (UC-MSCs), which have strong anti-inflammatory and repairing ability, to protect the integrity of BBB. BBB permeability was evaluated using dextran tracer (immunohistochemistry imaging and spectrophotometric quantification) and western blot, interleukin (IL)-6, and IL-1β levels in blood and brain were measured by enzyme-linked immunosorbent assay. Furthermore, transmission electron microscopy (TEM) was used to detect transcellular vesicular transport (transcytosis) in BBB. We found that burns increased mouse BBB permeability to both 10-kDa and 70-kDa dextran. IL-6 and IL-1β levels increased in peripheral blood and CNS after burns. In addition, burns decreased the level of tight junction proteins (TJs), including claudin-5, occludin, and ZO-1, which indicated increased BBB permeability due to paracellular pathway. Moreover, increased vesicular density after burns suggested increased transcytosis in brain microvascular endothelial cells. Finally, administering UC-MSCs at 1 h after burns effectively reversed these adverse effects and protected the integrity of BBB. These results suggest that burns increase BBB permeability through both paracellular pathway and transcytosis, the potential mechanism of which might be through increasing IL-6 and IL-1β levels and decreasing Mfsd2a level, and appropriate treatment with UC-MSCs can reverse these effects and protect the integrity of BBB after burns.

Chronic skin inflammatory diseases including atopic dermatitis (AD) and psoriasis have been considered uncontrolled inflammatory responses, which have usually troubled patients around the world. Moreover, the recent method to treat AD and psoriasis has been based on the inhibition, not regulation, of the abnormal inflammatory response, which can induce a number of side effects and drug resistance in long-term treatment. Mesenchymal stem/stromal cells (MSCs) and their derivatives have been widely used in immune diseases based on their regeneration, differentiation, and immunomodulation with few adverse effects, which makes MSCs a promising treatment for chronic skin inflammatory diseases. As a result, in this review, we aim to systematically discuss the therapeutic effects of various resources of MSCs, the application of preconditioning MSCs and engineering extracellular vesicles (EVs) in AD and psoriasis, and the clinical evaluation of the administration of MSCs and their derivatives, which can provide a comprehensive vision for the application of MSCs and their derivatives in future research and clinical treatment.