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In the early stages, patients with fractures often have massive bleeding, wasting coagulopathy, and injuries to other parts, but in the later stages, they are prone to various complications, leading to high mortality and disability. This study focuses on the preparation of nanomaterial graphene/chitosan scaffolds and their application in fracture treatment. This article first summarizes the current state of nanomaterial scaffolds, then describes their preparation methods, and finally describes their application in fracture treatment. In patients with fractures, the nanomaterial graphene/chitosan scaffold can provide a favorable rehabilitation environment at the fracture site. When combined with the auto repair ability of human tissues, it has the potential to accelerate patient recovery. The graphene/chitosan scaffold has a molecular structure similar to natural bone, making it more suitable for human bone rehabilitation than ordinary fixed scaffolds. The best time between stent implantation and surgery is half a month, which can significantly reduce the risk of postoperative complications. Reoperation for more than 18 days is an independent risk factor for local cancer recurrence. Therefore, using nanomaterial graphene/chitosan scaffolds in fracture treatment is safe, effective, and feasible. Further future research in this direction is warranted.

Transmembrane integrin receptors represent a major component of cell-extracellular matrix (ECM) communications that mediate cellular biological activities, including proliferation and differentiation. Stem cells, especially mesenchymal stem cells (MSC), have rapidly emerged as promising therapies for various diseases. Dynamic links exist between extracellular and intracellular environments that profoundly influence the cellular activities via integrin receptors, such as cell morphology transformation and differentiation. Interpreting the roles of integrin receptors in the regulation of MSC differentiation may potentially lead to an amplified therapeutic effect. In this review, we summarize, for the first time, the potential mechanisms by which integrins promote MSC multilineage differentiation, including integrin downstream signaling cascades and the interactions between integrin and ion channels, the cytoskeleton, and nuclear mechanoresponses. Furthermore, we focus on the current state and future prospects of the application of integrins to promote cell differentiation.

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release (FE@EVs) for improving motor functional recovery after SCI. The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases., Graphical abstract Image 1, Highlights • The novel FE hydrogel was designed for encapsulating the extracellular vesicles (FE@EVs). • FE hydrogel exert the capabilities of temperature-responsive, injectable, adhesive and biocompatible. • FE hydrogel with sustainable and long-term extracellular vesicle release for improving motor functional recovery after SCI. • FE@EVs plays a vital role in pathological process of spinal cord injury in rats.

Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Aucubin in SCI have not been reported.In this study, we carried out an in vivo SCI model and a series of in vitro experiments to explore the therapeutic effect of Aucubin. Western Blotting and immunofluorescence were used to study the effect of Aucubin on microglial polarization and neuronal apoptosis and its underlying mechanism.We found that Aucubin can promote axonal regeneration by reducing neuroinflammation and neuronal apoptosis, which is beneficial to motor recovery after spinal cord injury in rats. Our further in vitro experiments showed that Aucubin can activate the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/IκBα/nuclear factor kappa B (NF-κB) signaling pathway to reduce neuroinflammation and reverse mitochondrial dysfunction to reduce neuronal apoptosis.In summary, these results suggest that Aucubin may ameliorate secondary injury after SCI by reducing neuroinflammation and neuronal apoptosis. Therefore, Au may be a promising post-SCI therapeutic drug.

Nucleus pulposus (NP) degeneration is the major cause of degenerative disc disease (DDD). This condition cannot be treated or attuned by traditional open or minimally invasive surgical options. However, a combination of stem cells, growth factors (GFs) and biomaterials present a viable option for NP regeneration. Injectable biomaterials act as carriers for controlled release of GFs and deliver stem cells to target tissues through a minimally invasive approach. In this study, injectable Gelatin methacryloyl (GelMA) microspheres (GMs) with controllable, uniform particle sizes were rapidly biosythesized through a low-cost electrospraying method. The GMs were used as delivery vehicles for cells and GFs and they exhibited good mechanical properties, biocompatibilities and enhanced the in vitro differentiation of laden cells into NP-like phenotypes. Furthermore, this integrated system attenuated the in vivo degeneration of rat intervertebral disc, maintained NP tissue integrity and accelerated the synthesis of extracellular matrix (ECM). Therefore, this novel therapeutic system is a promising option for the treatment of Degenerative disc disease (DDD).

BackgroundPostmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast activation, and osteoclasts are considered to be the sole participants in the degeneration and resorption of bone matrix for controlling bone integrity and continuity. The biological functions of osteoclasts depend critically on the number and activity of fused polykaryon. Hence, targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Alpinetin is widely used for excellent anti-inflammatory activities and little side-effect, but its role in osteoporosis remains unknown.ResultsIn this study, we investigated for the first time the ability of alpinetin to inhibit estrogen deficiency-induced bone loss. Alpinetin significantly reduced the expression levels of NFATc1 and its downstream genes, thereby inhibiting osteoclast differentiation in a concentration- and time-dependent manner. Additionally, alpinetin inhibited F-actin ring formation and bone resorption, as well as reduced the activation levels of NF-κB, ERK, and AKT signaling cascades. In mature osteoclasts, alpinetin remarkably inhibited integrin-mediated migration and lysosomal biogenesis and trafficking by modulating the PKCβ/TFEB and ATG5/LC3 axes. Importantly, alpinetin treatment in mice alleviated ovariectomy-induced bone volume loss. ConclusionOur findings strongly suggest that alpinetin plays a significant role in the regulation of NFATc1 production for the differentiation of osteoclasts and inhibits integrin-mediated cell migration and lysosomal function in mature osteoclasts, thus weaken the increased osteolytic ability due to estrogen deficiency. Alpinetin may represent a promising agent for the treatment of osteoporosis and other metabolic bone diseases.

Inflammation and neuronal apoptosis aggravate the secondary damage after spinal cord injury (SCI). Rehmannioside A (Rea) is a bioactive herbal extract isolated from Rehmanniae radix with low toxicity and neuroprotection effects. Rea treatment inhibited the release of pro‐inflammatory mediators from microglial cells, and promoted M2 polarization in vitro, which in turn protected the co‐cultured neurons from apoptosis via suppression of the NF‐κB and MAPK signalling pathways. Furthermore, daily intraperitoneal injections of 80 mg/kg Rea into a rat model of SCI significantly improved the behavioural and histological indices, promoted M2 microglial polarization, alleviated neuronal apoptosis, and increased motor function recovery. Therefore, Rea is a promising therapeutic option for SCI and should be clinically explored.

Tendon injuries are common and require a long time to heal, and are particularly associated with some adverse problems such as adhesion and rupture. Herein, we aim to develop new bioactive scaffolds endowed with stem cell sheets and growth factors to enable cell migration and proliferation favorable for tendon regeneration in situ. An exogenous basic fibroblast growth factor (bFGF)-loaded fibrin gel was firstly incorporated into the porous network of knitted poly(lactide-co-glycolide) (PLGA) scaffolds and then sheets of mesenchymal stem cells (MSCs) were also integrated into the scaffolds. It was shown that the pores in the knitted PLGA scaffold were readily filled with a complex network of fibrin fiber gel and the fibrin fibers were beneficial for the controlled release of bFGF over a long time period. After transplantation in a critical-size Achilles tendon defect model (7 mm) in the rat right hindlimb, gross observation revealed no immunologic incompatibility or rejection derived from the scaffold systems. It was observed that the MSC sheets contributed directly to tendon regeneration, and exerted an environment-modifying effect on the injuries in situ, consistent with the beneficial effect of bFGF. It was interesting that the knitted PLGA-fibrin gel scaffolds loaded with MSC sheets and bFGF showed the highest expression of tendon-related gene markers and outstanding repair efficacy, including appreciable biomechanical strength and native-like histological microstructures. Therefore, the integration of MSC sheets and bFGF into PLGA/bFGF-fibrin gel scaffolds may stimulate the proliferation and tenogenic differentiation of MSCs in situ and synergistically enhance the injured tendon reconstruction.

Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1β, TNF-α, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.

Over-activated osteoclastogenesis, which is initiated by inflammation, has been implicated in osteoporosis. Corilagin, a natural compound extracted from various medicinal herbaceous plants, such as Cinnamomum cassia, has antioxidant and anti-inflammatory activities. We found that Corilagin suppressed osteoclast differentiation in a dose-dependent manner, significantly decreased osteoclast-related gene expression and impaired bone resorption by osteoclasts. Moreover, phosphorylation of members of the nuclear factor-kappaB (NF-κB) and PI3K/AKT signalling pathways was reduced by Corilagin. In a murine model of osteoporosis, Corilagin inhibited osteoclast functions in vivo and restored oestrogen deficiency-induced bone loss. In conclusion, our findings suggested that Corilagin inhibited osteoclastogenesis by down-regulating the NF-κB and PI3K/AKT signalling pathways, thus showing its potential possibility for the treatment of osteoporosis.

Gelatin methacrylate (GelMA)-based hydrogels are gaining a great deal of attention as potentially implantable materials in tissue engineering applications because of their biofunctionality and mechanical tenability. Since different natural tissues respond differently to mechanical stresses, an ideal implanted material would closely match the mechanical properties of the target tissue. In this regard, applications employing GelMA hydrogels are currently limited by the low mechanical strength and biocompatibility of GelMA. Therefore, this review focuses on modifications made to GelMA hydrogels to make them more suitable for tissue engineering applications. A large number of reports detail rational synthetic processes for GelMA or describe the incorporation of various biomaterials into GelMA hydrogels to tune their various properties, e.g., physical strength, chemical properties, conductivity, and porosity, and to promote cell loading and accelerate tissue repair. A novel strategy for repairing tissue injuries, based on the transplantation of cell-loaded GelMA scaffolds, is examined and its advantages and challenges are summarized. GelMA-cell combinations play a critical and pioneering role in this process and could potentially accelerate the development of clinically relevant applications.