Extracellular Matrix-Based Conductive Interpenetrating Network Hydrogels with Enhanced Neurovascular Regeneration Properties for Diabetic Wounds Repair.

The critical effects that impair diabetic wound healing are characterized by poor vascularization and severe peripheral neuropathy. Current management strategies for diabetic wound healing are unsatisfactory, due to the paucity of neurovascular regeneration at the wound site. Importantly, conductivity in skin tissue is reported to be essential for modulating myriad biological processes especially vascular and nerve regeneration. Herein, an extracellular matrix (ECM)-based conductive dressing is synthesized from an interpenetrating polymer network hydrogel composed of gelatin methacryloyl, oxidized chondroitin sulfate (OCS), and OCS-polypyrrole conductive nanoparticles that can promote diabetic wound repairing by enhancing local neurovascular regeneration. The conductive hydrogels combine the advantageous features of water-swollen hydrogels with conductive polymers (CPs) to provide tissue-matching electrical conductivity and mechanical properties for neurovascular regeneration. In vitro and in vivo studies show that the conductive hydrogel can promote neurovascular regeneration by increasing intracellular Ca2+ concentration, which subsequently promotes phosphorylation of proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Furthermore, the conductive hydrogel stimulates full-thickness diabetic wound repair on day 14 by promoting local neurovascular regeneration and collagen deposition. These findings corroborate that the ECM-based conductive interpenetrating network hydrogel dressing significantly promotes wound repairing due to its neurovascular regeneration properties, suggesting that they are suitable candidates for diabetic wound repair.

Surgery vs conservative treatment for type II and III odontoid fractures in a geriatric population: A meta-analysis.

BACKGROUND: It is unclear whether surgery or conservative treatment is more suitable for elderly patients with type II and type III odontoid fractures. We performed this meta-analysis to compare the efficacy of surgical and conservative treatments for type II and type III odontoid fractures. METHODS: A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Library in January 2017. Only articles comparing surgery with conservative treatment in elderly patients with type II and type III odontoid fractures were selected. After 2 authors independently assessed the retrieved studies, 18 articles were included in this meta-analysis, and the primary endpoints were the nonunion rate and mortality rate. The secondary outcomes were patient satisfaction, complications, and the length of the hospital stay. The quality of the included studies was evaluated using the modified Newcastle-Ottawa scale. Sensitivity analyses were performed for high-quality studies, and the publication bias was evaluated using a funnel plot. RESULTS: Lower nonunion (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.18-0.40, P < .05) and mortality rates (OR: 0.52, 95% CI: 0.34-0.79, P < .05) confirmed the superiority of surgery in treating type II and type III fractures. The secondary outcomes differed. Patients in the surgery group felt more satisfied with the outcome (OR: 3.44, 95% CI: 1.19-9.95, P < .05), and the complications were similar in the 2 groups (OR: 1.14, 95% CI: 0.78-1.68, P = .5), whereas patients in conservative groups spent less time in the hospital (OR: 5.10, 95% CI: 2.73-7.47, P < .05). The results of the subgroup analyses and sensitivity analysis were similar to the original outcomes, and no obvious publication bias was observed in the funnel plot. CONCLUSION: Most elderly (younger than 70 years) patients with type II or type III odontoid fractures should be considered candidates for surgical treatment, due to the higher union rate and lower mortality rate, while statistically significant differences were not observed in the population with an advanced age (older than 70 years). Therefore, the selection of the therapeutic approach for elderly patients with odontoid fractures requires further exploration. Simultaneously, based on our meta-analysis, a posterior arthrodesis treatment was significantly superior to the anterior odontoid screw treatment.

Soft Conducting Polymer Hydrogels Cross-Linked and Doped by Tannic Acid for Spinal Cord Injury Repair.

Mimicking soft tissue mechanical properties and the high conductivity required for electrical transmission in the native spinal cord is critical in nerve tissue regeneration scaffold designs. However, fabricating scaffolds of high conductivity, tissue-like mechanical properties, and excellent biocompatibility simultaneously remains a great challenge. Here, a soft, highly conductive, biocompatible conducting polymer hydrogel (CPH) based on a plant-derived polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord injury (SCI). The developed hydrogels exhibit an excellent electronic conductivity (0.05-0.18 S/cm) and appropriate mechanical properties (0.3-2.2 kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with a higher conductivity accelerated the differentiation of neural stem cells (NSCs) into neurons while suppressing the development of astrocytes. In vivo, with relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in the lesion area, resulting in significant recovery of locomotor function. Overall, our findings evidence that the CPHs without being combined with any other therapeutic agents have stimulated tissue repair following an SCI and thus have important implications for future biomaterial designs for SCI therapy.

[Different adhesion rate of sheep BMSCs on copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate before and after photografting modification in vitro].

OBJECTIVE: To evaluate the biocompatibility of the sheep BMSCs cultured on the surface of photografting modified copolymers of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV). METHODS: BMSCs were isolated from bone marrow of the posterior iliac crest of a 6-month old sheep by whole marrow adherent culture method. The 3rd passage BMSCs were seeded onto modified PHBV and conventional PHBV films, or three-dimension scaffolds. Cell-adhesion rates were calculated by hemocytometer at 1, 2 and 6 hours after seeded. Cell morphology was examined by scanning electron microscope when the BMSCs were cultured for 3 days, 1 week and 3 weeks. Cell cycle was analyzed by flow cytometry at 5 days after seeded. The content of protein in BMSCs was determined by BCA assay and the content of DNA was quantified by Hoechst 33258 assay at 4, 8 and 12 days after seeded. RESULTS: At 1 hour after seeded, cell-adhesion rate on modified PHBV films (52.7% +/- 6.0%) was significantly higher than that of conventional PHBV films (37.5% +/- 5.3%) (P < 0.05); At 2 and 6 hours after seeded, cell-adhesion rate of modified PHBV films was similar to that of PHBV films (P > 0.05). The surface of modified PHBV film was rougher. In the early culture stage, more cells adhered to modified PHBV and the cells displayed much greater spreading morphology. Furthermore, ECM on modified PHBV were richer. There were no significant differences between the trial team and the control on the cell cycle and the content of DNA and protein of BMSCs (P > 0.05). CONCLUSION: Photografting modification on PHBV can promote BMSCs' adhesion and enhance their biocompatibility.