Multi-functional dual-layer nanofibrous membrane for prevention of postoperative pancreatic leakage.

Postoperative pancreatic leakage due to pancreatitis in patients is a life-threatening surgical complication. The majority of commercial barriers are unable to meet the demands for pancreatic leakage due to poor adhesiveness, toxicity, and inability to degrade. In this study, we fabricated mitomycin-c and thrombin-loaded multifunctional dual-layer nanofibrous membrane with a combination of alginate, PCL, and gelatin to resolve the leakage due to suture line disruption, promote hemostasis, wound healing, and prevent postoperative tissue adhesion. Electrospinning was used to fabricate the dual-layer system. The study results demonstrated that high gelatin and alginate content in the inner layer decreased the fiber diameter and water contact angle, and crosslinking allowed the membrane to be more hydrophilic, making it highly biodegradable, and adhering firmly to the tissue surfaces. The results of in vitro biocompatibility and hemostatic assay revealed that the dual-layer had a higher cell proliferation and showed effective hemostatic properties. Moreover, the in vivo studies and in silico molecular simulation indicated that the dual layer was covered at the wound site, prevented suture disruption and leakage, inhibited hemorrhage, and reduced postoperative tissue adhesion. Finally, the study results proved that dual-layer multifunctional nanofibrous membrane has a promising therapeutic potential in preventing postoperative pancreatic leakage.

Small-diameter vascular graft composing of core-shell structured micro-nanofibers loaded with heparin and VEGF for endothelialization and prevention of neointimal hyperplasia.

Despite the significant progress made in recent years, clinical issues with small-diameter vascular grafts related to low mechanical strength, thrombosis, intimal hyperplasia, and insufficient endothelialization remain unresolved. This study aims to design and fabricate a core-shell fibrous small-diameter vascular graft by co-axial electrospinning process, which will mechanically and biologically meet the benchmarks for blood vessel replacement. The presented graft (PGHV) comprised polycaprolactone/gelatin (shell) loaded with heparin-VEGF and polycaprolactone (core). This study hypothesized that the shell structure of the fibers would allow rapid degradation to release heparin-VEGF, and the core would provide mechanical strength for long-term application. Physico-mechanical evaluation, in vitro biocompatibility, and hemocompatibility assays were performed to ensure safe in vivo applications. After 25 days, the PGHV group released 79.47 ± 1.54% of heparin and 86.25 ± 1.19% of VEGF, and degradation of the shell was observed but the core remained pristine. Both the control (PG) and PGHV groups demonstrated robust mechanical properties. The PGHV group showed excellent biocompatibility and hemocompatibility compared to the PG group. After four months of rat aorta implantation, PGHV exhibited smooth muscle cell regeneration and complete endothelialization with a patency rate of 100%. The novel core-shell structured graft could be pivotal in vascular tissue regeneration application.

Physico-biological evaluation of 3D printed dECM/TOCN/alginate hydrogel based scaffolds for cartilage tissue regeneration.

Cartilage damage is the leading cause of osteoarthritis (OA), especially in an aging society. Mimicking the native cartilage microenvironment for chondrogenic differentiation along with constructing a stable and controlled architectural scaffold is considerably challenging. In this study, three-dimensional (3D) printed scaffolds using tempo-oxidized cellulose nanofiber (TOCN), decellularized extracellular matrix (dECM), and sodium alginate (SA) were fabricated for cartilage tissue regeneration. We prepared three groups (dECM80, dECM50, dECM20) of 3D printable hydrogels with different ratios of TOCN and dECM where SA concentration remained the same. Two-step crosslinking was performed with CaCl2 solution to achieve the highly stable 3D printed scaffolds. Finally, the fundamental physical characterizations showed that increasing the ratio of TOCN with dECM significantly improved the viscoelastic behaviour, stability, mechanical properties, and printability of the scaffolds. Based on the results, the 3D printed dECM50 scaffolds with controlled and identical pore sizes increased the whole-layer integrity and nutrient supply in each layer of the scaffold. Furthermore, evaluation of in vitro and in vivo biocompatibility of the scaffolds with rBMSCs indicated that dECM50 scaffolds provided a suitable microenvironment for cell proliferation and promoted chondrogenesis by remarkably expressing the cartilage-specific markers. This study demonstrates that 3D printed dECM50 scaffolds provide a favourable and promising microenvironment for cartilage tissue regeneration.

Crosstalk between xanthine oxidase (XO) inhibiting and cancer chemotherapeutic properties of comestible flavonoids- a comprehensive update.

Gout is an inflammatory disease caused by metabolic disorder or genetic inheritance. People throughout the world are strongly dependent on ethnomedicine for the treatment of gout and some receive satisfactory curative treatment. The natural remedies as well as established drugs derived from natural sources or synthetically made exert their action by mechanisms that are closely associated with anticancer treatment mechanisms regarding inhibition of xanthine oxidase, feedback inhibition of de novo purine synthesis, depolymerization and disappearance of microtubule, inhibition of NF-ĸB activation, induction of TRAIL, promotion of apoptosis, and caspase activation and proteasome inhibition. Some anti-gout and anticancer novel compounds interact with same receptors for their action, e.g., colchicine and colchicine analogues. Dietary flavonoids, i.e., chrysin, kaempferol, quercetin, fisetin, pelargonidin, apigenin, luteolin, myricetin, isorhamnetin, phloretinetc etc. have comparable IC50 values with established anti-gout drug and effective against both cancer and gout. Moreover, a noticeable number of newer anticancer compounds have already been isolated from plants that have been using by local traditional healers and herbal practitioners to treat gout. Therefore, the anti-gout plants might have greater potentiality to become selective candidates for screening of newer anticancer leads.