There is an urgent demand for wound healing biomaterials because of the increasing frequency of traffic accidents, industrial contingencies, and natural disasters. Borate bioactive glass has potential applications in bone tissue engineering and wound healing; however, its uncontrolled release runs a high risk of rapid degradation and transient biotoxicity. In this study, a novel organic-inorganic dressing of copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) loaded with vitamin E (0-3.0 wt % vitamin E) was fabricated to evaluate its efficiency for angiogenesis in cells and full-thickness skin wounds healing in rodents. In vitro results showed the dressing was an ideal interface for the organic-inorganic mixture and a controlled release system for Cu and vitamin E. Cell culture suggested the ionic dissolution product of the copper-doped and vitamin E-loaded dressing showed the best migration, tubule formation, and vascular endothelial growth factor (VEGF) secretion in human umbilical vein endothelial cells (HUVECs) and higher expression levels of angiogenesis-related genes in fibroblasts in vitro. Furthermore, this dressing also suggested a significant improvement in the epithelialization of wound closure and an obvious enhancement in vessel sprouting and collagen remodeling in vivo. These results indicate that the copper-doped borate bioactive glass/poly(lactic- co-glycolic acid) dressing loaded with vitamin E is effective in stimulating angiogenesis and healing full-thickness skin defects and is a promising wound dressing in the reconstruction of full-thickness skin injury.
Our previous studies showed that silent mating-type information regulation 2 homologue-1 (SIRT1, a deacetylase) upregulation could attenuate sepsis-induced acute kidney injury (SAKI). Upregulated SIRT1 can deacetylate certain autophagy-related proteins (Beclin1, Atg5, Atg7 and LC3) in vitro. However, it remains unclear whether the beneficial effect of SIRT1 is related to autophagy induction and the underlying mechanism of this effect is also unknown. In the present study, caecal ligation and puncture (CLP)-induced mice, and an LPS-challenged HK-2 cell line were established to mimic a SAKI animal model and a SAKI cell model, respectively. Our results demonstrated that SIRT1 activation promoted autophagy and attenuated SAKI. SIRT1 deacetylated only Beclin1 but not the other autophagy-related proteins in SAKI. SIRT1-induced autophagy and its protective effect against SAKI were mediated by the deacetylation of Beclin1 at K430 and K437. Moreover, two SIRT1 activators, resveratrol and polydatin, attenuated SAKI in CLP-induced septic mice. Our study was the first to demonstrate the important role of SIRT1-induced Beclin1 deacetylation in autophagy and its protective effect against SAKI. These findings suggest that pharmacologic induction of autophagy via SIRT1-mediated Beclin1 deacetylation may be a promising therapeutic approach for future SAKI treatment.
A combination of chemotherapy and photothermal therapy (PTT) has emerged as a promising strategy for cancer therapy. To ensure that the chemotherapeutic drug and photothermal agent can be simultaneously delivered to the tumor site to exert their synergistic effects, a safe and efficient delivery system is needed. Herein, we fabricated doxorubicin hydrochloride (DOX)- and indocyanine green (ICG)-loaded microneedle (MN) patches (PVP@DOX/MSN@ICG) using a two-step casting process. Mesoporous silica nanoparticles (MSNs) were used to improve the ICG stability and avoid reducing its PTT efficiency in vivo. The MN patches exhibited a good skin penetration ability, and the tips of the MN patches were dissolved by the interstitial fluid to release DOX and ICG at the tumor sites. Under 808 nm laser irradiation within 2 min, the local temperature in the tumor quickly reached 48 °C at a low power of 0.34 W cm-2. A combination of chemotherapy and PTT for PVP@DOX/MSN@ICG MN patches may maximally induce human osteosarcoma MG-63 cells in vitro. Moreover, the in vivo results showed that PVP@DOX/MSN@ICG MN patches had the best antitumor effects because of synergistic chemotherapy and PTT. Therefore, the composite-dissolving MN patch is a promising strategy for enhancing the antitumor effect of chemotherapy alone and shows the potential for the synergistic therapy of superficial tumors.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.