Alloy nanozyme-reinforced hyaluronic acid-based hydrogel with wound environment-responsive properties for synergistically accelerating infectious wound healing.

The recovery of infectious wound tissues presents a significant global health challenge due to the impediments posed by the harsh healing microenvironment, which includes ongoing bacterial invasion, high oxidative stress, inflammatory response, and impaired angiogenesis. To overcome the above issues, we propose a composite hydrogel based on the multiple-crosslinked mechanism involving the covalent network of CC bonds within catechol and maleic-modified HA (CMHA), the self-assembly network of glycyrrhizic acid (GA), and the metal-polyphenol coordination induced by ZHMCe for accelerating infectious wound healing. The resulting CMHA/GA/ZHMCe hydrogels demonstrate enhanced mechanical, adhesive, antioxidative, and antibacterial properties. Importantly, the hydrogel system possesses wound environment-responsive properties that allow it to adapt to the specific therapeutic requirements of different stages by regulating various enzyme activities in the healing of infected wounds. Furthermore, the biocompatible CMHA/GA/ZHMCe shows the ability to promote cell migration and angiogenesis in vitro while reprogramming macrophages toward an anti-inflammatory phenotype due to the effective release of active ingredients. In vivo experiments confirm that the CMHA/GA/ZHMCe hydrogel significantly enhances infectious wound healing by accelerating re-epithelialization, promoting collagen deposition, regulating inflammation, and contributing to vascularization. These findings underscore the therapeutic potential of our hydrogel dressings for the treatment of bacterially infected cutaneous wound healing.

Enhancing neuroprotective effect of aminosalicylic acid-grafted chitosan electrospun fibers for spinal cord injury.

The hyperinflammation microenvironment after spinal cord injury (SCI) remains a great challenge for neural regeneration. Methylprednisolone has been used to reduce the inflammatory response after SCI, but it is controversial due to side effects associated with off-specific targeting effects. In this study, we synthesized in situ 5-ASA grafted chitosan electrospun fibers (ASA-EF) with excellent injectable and self-healing properties to reprogram nerve cells via displaying biological distribution, gene expression, and functional changes. With the support of ASA-EF, the downregulation of inflammatory cytokines expression and the upregulation of anti-inflammatory and regenerative gene expression were found in vitro studies. Moreover, ASA-EF administration polarized macrophages toward proregenerative phenotypes in the injured lesion, and significantly reduced cavity area. In addition, ASA-EF administration increased myelination and regenerating axons and improved motor function (score of 5 versus 2 for SCI group). These results illustrate that the neuroprotective effect of this artificial nanoplatform will facilitate the clinical treatment of traumatic-related diseases via forming a recycled microenvironment that supports regeneration and functional recovery. These particles may be applied to trauma and potential other inflammatory diseases.

Gold nanoclusters conjugated berberine reduce inflammation and alleviate neuronal apoptosis by mediating M2 polarization for spinal cord injury repair.

Spinal cord injury (SCI) leads to nerve cell apoptosis and loss of motor function. Herein, excessive activation of the M1 phenotype macrophages/microglia is found to be the main reason for the poor prognosis of SCI, but the selective activation phenotype (M2) macrophages/microglia facilitates the recovery of SCI. Thereafter, we used gold nanoclusters loaded berberine (BRB-AuNCs) to reduce inflammation by inhibiting the activation of M1 phenotype macrophages/microglia, which simultaneously inhibited neuronal apoptosis after SCI. In vitro and in vivo experiments showed that BRB-AuNCs reduced M1 protein marker CD86, increased M2 protein marker CD206, reduced inflammation and apoptotic cytokines (IL-1ß, IL-6, TNF-α, Cleaved Caspase-3 and Bax). These results indicate that BRB-AuNCs have excellent anti-inflammatory and anti-apoptotic effects by inducing the polarization of macrophages/microglia from M1 phenotype to M2 phenotype. Thereafter, the motor functions of SCI rats were significantly improved after treatment with BRB-AuNCs. This work not only provides a new way for the treatment of SCI but also broadens BRB utilization strategies.

Whole body vibration remodels skeletal muscle via autophagy and energy metabolism in diabetic mice.

Hyperglycemia occurs due to a defect in insulin secretion or impaired biological functions, or both. The long­term hyperglycemia during diabetes causes chronic damage and dysfunction of various tissues. Whole body vibration (WBV) has significant effects on lipid and glucose metabolism and endocrine and motor systems. In order to explore the effects of WBV on skeletal muscle, mice trained for 12 weeks with WBV (15 Hz, 30 min) were used as experimental subjects and their skeletal muscle morphology under the pathological state of diabetes was observed. In addition, the blood lipids, blood glucose, gastrocnemius muscle glycogen and mRNA and protein levels of autophagy and glucose metabolism biomarkers were compared among the three groups of mice via western blot and RT­qPCR. The results showed that WBV can significantly reshape skeletal muscle morphology and upregulate high density lipoprotein. The expression of glucose­6­phosphatase (G6P), Beclin1 and Atg7 in the gastrocnemius muscle of the WBV group was significantly increased. Therefore, it can be concluded that WBV promotes skeletal muscle remodeling in diabetic mice. The present study confirmed that WBV can attenuate the development of diabetes melitus (DM) and lead to lower level low density lipoprotein in the blood. In addition, G6P level plays an important role in WBV­treated DM model and may be used to monitor the effect of WBV in patients. The findings of the present study may provide a new molecular basis for WBV to play a therapeutic role in the treatment of diabetes and may have potential clinical applications in the future.

Retraction: Efficient in vivo wound healing using noble metal nanoclusters.

Retraction of 'Efficient in vivo wound healing using noble metal nanoclusters' by Kuo Li et al. Nanoscale, 2021, 13, 6531-6537. DOI: 10.1039/D0NR07176E.

Repair calvarial defect of osteoporotic rats by berberine functionalized porous calcium phosphate scaffold.

In this article, we propose a simple scheme of using berberine (BBR) to modify porous calcium phosphate ceramics (named PCPC). These BBR molecules regulate the crystallization of hydroxyapatite nanorods on PCPC. We found that these nanorods and the adsorbed BBR changed the interface micro-environment of PCPC by SEM images. The microenvironment of PCPC surface is essential for promoting BMSCs' proliferation and differentiation. These results demonstrated that PCPC/BBR markedly improved the bone regeneration of osteoporosis rats. Moreover, PCPC/BBR had significantly increased the expression levels of ALP, osteocalcin and bone morphogenetic protein2 and RUNX2 in BMSCs originated from osteoporosis rats.

Efficient in vivo wound healing using noble metal nanoclusters.

The wound healing process involves multiple steps including hemostasis, inflammation, proliferation, and tissue remodeling. Nanomaterials have been employed externally for healing wounds. However, their use as systemic therapeutics has not been extensively explored. We report the use of ultra-small noble metal nanoclusters (NCs) for the treatment of skin wounds. Both in vitro and in vivo studies indicate NCs have comprehensive therapeutic effects for wound healing, promoting cell proliferation and migration while decreasing inflammation.

Bioengineered Zinc Oxide Nanoparticle-Loaded Hydrogel for Combinative Treatment of Spinal Cord Transection.

Spinal cord injury (SCI) is one of the most destructive diseases. The neuroinflammation microenvironment needs comprehensive mitigation of damages. Thus, regulation of local, microenvironment drugs could be a potential effective treatment. However, clinical studies on SCI with common treatment have reported it to cause systemic toxicity and side effects. Zinc oxide nanoparticles (ZnONPs) have been widely reported to have satisfying anti-inflammation function. Furthermore, green synthesis procedures can improve the capability and possible utilization of ZnONPs. However, the efficient administration and underlying mechanism of ZnONPs in SCI treatment remain unclear. Herein, an innovative approach was built by utilizing ZnONPs loaded in a skeletal muscle-derived adhesive hydrogel (ZnONPs-Gel). Different from the systemic application of ZnONPs, the local administration of ZnONPs-Gel offered the ZnONPs-loaded extracellular matrix with beneficial biocompatibility to the injured spinal cord, thereby promoting effective function recovery. Mechanistically, the ZnONPs-Gel treatment not only markedly reduced ROS production but also decreased apoptosis in the injured spinal cord. Therefore, the strategy based on local administration of the ZnONPs-Gel in the early stage of SCI may be an effective therapeutic treatment.

Encapsulation of green tea polyphenol nanospheres in PVA/alginate hydrogel for promoting wound healing of diabetic rats by regulating PI3K/AKT pathway.

Difficult healing of skin wounds is one of the serious complications of diabetes mellitus. Green tea polyphenols (TP) have been found to have good therapeutic effects on wounds healing. However, TP that is soluble in water and easily been oxidized requires a gel material that provides moisture retention, oxidation prevention, and sustained release of TP to achieve better wound healing effect. Therefore, in this work, novel tea polyphenol nanospheres (TPN) were synthesized and encapsulated in a PVA /alginate hydrogel (TPN@H). The prepared TPN@H was characterized and applicated in model diabetic rats for promoting wound healing and regulating immune response. Fourier-transform infrared spectroscopy (FT-IR), UV spectroscopy, scanning electron microscopy (SEM), atomic force microscope (AFM), confocal laser scanning microscopy (CLSM), dynamic light scattering (DLS) and differential scanning calorimetry (DSC) were used for characterization. Animal experiments and molecular mechanism research proved that TPN@H could promote wound healing of diabetic rats by regulating PI3K/AKT signaling pathway.