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Angiogenesis in the field of tissue engineering has attracted significant attention. Graphene oxide has become a promising nanomaterial in tissue engineering for its unique biochemical properties. Therefore, herein, a series of chitosan (CS)/graphene oxide (GO) hydrogel scaffolds were synthesized by crosslinking CS and GO at different concentrations (0.1, 0.5, and 1.0 wt.%) using genipin. Compared with the CS hydrogel scaffolds, the CS/GO hydrogel scaffolds have a better network structure and mechanical strength. Then, we used endothelial progenitor cells (EPCs) extracted from human umbilical cord blood and cocultured these EPCs with the as-prepared scaffolds. The scaffolds with 0.1 and 0.5 wt.%GO showed no considerable cytotoxicity, could promote the proliferation of EPCs and tube formation, and upregulated the expressions of CD34, VEGF, MMP9, and SDF-1 in EPCs compared to the case of the scaffold with 1.0 wt.%GO. This study shows that the addition of graphene oxide improves the structure of chitosan hydrogel and enhances the proliferation activity and angiogenic capacity of EPCs.

Background: Diabetic foot is caused by ischemic disease of lower extremities of diabetic patients, and the effective therapy is very limited. Mesenchymal stem cells (MSCs) based cell therapy had been developed into a new treatment strategy for diabetic foot clinically. However, the underlying molecular mechanism remains to be fully addressed. Exosomes secreted by MSCs may play crucial role in the processes of MSCs mediated inhibition of inflammatory microenvironment as well as pro-angiogenesis of ischemic tissue of diabetic foot. Methods: Exosomes were isolated from MSCs using ultra-high centrifugation, and further characterized by the nanoparticle tracking analyzer and flow cytometry. Moreover, RNA sequencing, Western Blot, in vitro cell proliferation, in vivo pro-angiogenesis, as well as ischemic repairment of diabetic foot through rat model were performed to evaluate exosome physiological functions. Results: We found that different inflammatory cytokines (tumor necrosis factor a, vascular cell adhesion molecule-1 and interleukin-6) induced MSCs to secrete exosomes heterogeneously, including exosome size and quantity. Through RNA sequencing, we defined a new proangiogenic miRNA, miRNA-21-5p. Further knockdown and overexpression of miRNA-21-5p by manipulating MSCs validated the biological activity of exosome miRNA-21-5p, including in vitro cell proliferation, in vivo pro-angiogenesis in Chick Chorioallantoic Membrane (CAM) assay, and in vivo pro-angiogenesis experiments (tissue injury and repair) in diabetic rat models. Furthermore, we discovered that exosomemiRNA-21-5p promoted angiogenesis through upregulations of vascular endothelial growth factor receptor (VEGFR) as well as activations of serine/threonine kinase (AKT) and mitogen-activated protein kinase (MAPK). Together, our work suggested miRNA-21-5p could be a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis. Meanwhile, miRNA-21-5p could be potentially developed into a new biomarker for exosomes of MSCs to treat diabetic foot. Conclusions: miRNA-21-5p is a new biomarker and a novel mechanism by which exosomes promote ischemic tissue repairing and angiogenesis of diabetic foot. Our work could not only provide new scientific evidences for revealing pro-angiogenesis mechanism of MSCs, but also eventually benefit MSCs-based clinical therapy for diabetic foot of diabetes patients.

Background The efficacy of erector spinae plane block (ESPB) for pain control in other surgeries remains an interesting topic of discussion. This study aimed to evaluate the safety and efficacy and quality of recovery of ultrasound-guided bilateral ESPB in laparoscopic surgery for colon cancer. Material and methods In this study 50 patients were included and randomly divided into the intervention group (E group, n = 25) and the control group (C group, n = 25). Patients in the E group received general anesthesia with preoperative bilateral ultrasound-guided ESPB, whereas patients in the C group received general anesthesia with saline injection in the erector spinae plane preoperatively. Data on intraoperative and postoperative anesthetic effects and the effect on enhanced recovery after surgery were recorded and analyzed. Results Rocuronium consumption in the intervention group was 82.80 ± 21.70 mg, which was lower than that in the control group (P < 0.05). Visual analog scale scores at 2, 6, and 24 h after surgery in the intervention group were lower than those in the control group (Fbetween = 34.034, P = 0.000). The time to ambulation, consumption of ketorolac tromethamine, time to oral intake and hospital stay after operation in the intervention group were significantly lower than those in the control group (P < 0.05). The block area at the different baselines was significant (Fbetween = 3.211, P = 0.009). The association between baseline and time was significant (Fbaseline * time = 3.268, P = 0.001). Conclusion This study confirmed that ultrasound-guided ESPB technology is safe and beneficial for patients with colon cancer undergoing laparoscopic colon surgery.