Multifunctional nanocomposites mediated novel hydrogel for diabetic wound repair.

The regeneration and repair of diabetic wounds, especially those including bacterial infection, have always been difficult and challenging using current treatment. Herein, an effective strategy is reported for constructing glucose-responsive functional hydrogels using nanocomposites as nodes. In fact, tannic acid (TA)-modified ceria nanocomposites (CNPs) and a zinc metal-organic framework (ZIF-8) were employed as nodes. Subsequent crosslinking with 3-acrylamidophenylboronic acid achieved functional nanocomposite-hydrogels (TA@CN gel, TA@ZMG gel) by radical-mediated polymerization. Compared with a simple physically mixed hydrogel system, the mechanical properties of TA@CN gel and TA@ZMG gel are significantly enhanced due to the intervention of the nanocomposite nodes. In addition, this kind of nanocomposite hydrogel can realize the programmed loading of drugs and release of drugs in response to glucose/PH, to coordinate and promote its application in the regeneration and repair of diabetic wounds and infected diabetic wounds. Specifically, TA@CN gel can remove reactive oxygen species and generate oxygen through its various enzymatic activities. At the same time, it can effectively promote neovascularization, thus promoting the regeneration and repair of diabetic wounds. Furthermore, glucose oxidase-loaded TA@ZMG gel exhibits glucose response and pH-regulating functions, triggering programmed metformin (Met) release by degrading the metal-organic framework (MOF) backbone. It also exhibited additional synergistic effects of antibacterial activity, hair regeneration and systemic blood glucose regulation, which make it suitable for the repair of more complex infected diabetic wounds. Overall, this novel nanocomposite-mediated hydrogel holds great potential as a biomaterial for the healing of chronic diabetic wounds, opening up new avenues for further biomedical applications.

A hydrogel system for drug loading toward the synergistic application of reductive/heat-sensitive drugs.

The preparation of hydrogels as drug carriers via radical-mediated polymerization has significant prospects, but the strong oxidizing ability of radicals and the high temperatures generated by the vigorous reactions limits the loading for reducing/heat-sensitive drugs. Herein, an applicable hydrogel synthesized by radical-mediated polymerization is reported for the loading and synergistic application of specific drugs. First, the desired sol is obtained by polymerizing functional monomers using a radical initiator, and then tannic-acid-assisted specific drug mediates sol-branched phenylboric acid group to form the required functional hydrogel (New-gel). Compared with the conventional single-step radical-mediated drug-loading hydrogel, the New-gel not only has better chemical/physical properties but also efficiently loads and releases drugs and maintains drug activity. Particularly, the New-gel has excellent loading capacity for oxygen, and exhibits significant practical therapeutic effects for diabetic wound repair. Furthermore, owing to its high light transmittance, the New-gel synergistically promotes the antibacterial effect of photosensitive drugs. This gelation strategy for loading drugs has further promising biomedical applications.

Functional molecule-mediated assembled copper nanozymes for diabetic wound healing.

BACKGROUND: The complex hyperglycemic, hypoxic, and reactive oxygen species microenvironment of diabetic wound leads to vascular defects and bacterial growth and current treatment options are relatively limited by their poor efficacy. RESULTS: Herein, a functional molecule-mediated copper ions co-assembled strategy was constructed for collaborative treatment of diabetic wounds. Firstly, a functional small molecule 2,5-dimercaptoterephthalic acid (DCA) which has symmetrical carboxyl and sulfhydryl structure, was selected for the first time to assisted co-assembly of copper ions to produce multifunctional nanozymes (Cu-DCA NZs). Secondly, the Cu-DCA NZs have excellent multicatalytic activity, and photothermal response under 808 nm irradiation. In vitro and in vivo experiments showed that it not only could efficiently inhibit bacterial growth though photothermal therapy, but also could catalyze the conversion of intracellular hydrogen peroxide to oxygen which relieves wound hypoxia and improving inflammatory accumulation. More importantly, the slow release of copper ions could accelerate cellular proliferation, migration and angiogenesis, synergistically promote the healing of diabetic wound furtherly. CONCLUSIONS: The above results indicate that this multifunctional nanozymes Cu-DCA NZs may be a potential nanotherapeutic strategy for diabetic wound healing.

Copper-rich multifunctional Prussian blue nanozymes for infected wound healing.

The healing process of infected wounds was limited by bacterial infection, excessive reactive oxygen species (ROS) accumulation, and tissue hypoxia. In order to alleviate the above situations, herein, a copper-rich multifunctional ultra-small Prussian blue nanozymes (HPP@Cu NZs) was constructed for infected wound synergistic treatment. Firstly, hyaluronic acid was modified by branched polyethyleneimine which could form a complex with copper ions, to construct copper-rich Prussian blue nanozymes. Secondly, the HPP@Cu NZs have a uniform ultra-small nano size and excellent photothermal response performance, exhibition of multifunctional enzymatic activity and anti-inflammatory properties. Finally, the slow release of copper ions in the HPP@Cu NZs could effectively promote the formation of new blood vessels, thus giving it multifunctional properties. In vitro and in vivo experiments showed that it not only could effectively inhibit and kill bacteria under 808 nm near-infrared laser but also could remove excessive ROS, regulate oxygen levels, and anti-inflammation. More importantly, the release of copper ions could synergistically promote the healing of infected wounds as well as good biocompatibility. Overall, our studies provide a multifunctional strategy for infected wounds with synergistic treatment based on carrier construction.

Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center.

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.