Nanoengineered 3D-printing scaffolds prepared by metal-coordination self-assembly for hyperthermia-catalytic osteosarcoma therapy and bone regeneration.

The integration of functional nanomaterials with tissue engineering scaffolds has emerged as a promising solution for simultaneously treating malignant bone tumors and repairing resected bone defects. However, achieving a uniform bioactive interface on 3D-printing polymer scaffolds with minimized microstructural heterogeneity remains a challenge. In this study, we report a facile metal-coordination self-assembly strategy for the surface engineering of 3D-printed polycaprolactone (PCL) scaffolds with nanostructured two-dimensional conjugated metal-organic frameworks (cMOFs) consisting of Cu ions and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP). A tunable thickness of Cu-HHTP cMOF on PCL scaffolds was achieved via the alternative deposition of metal ions and HHTP. The resulting composite PCL@Cu-HHTP scaffolds not only demonstrated potent photothermal conversion capability for efficient OS ablation but also promoted the bone repair process by virtue of their cell-friendly hydrophilic interfaces. Therefore, the cMOF-engineered dual-functional 3D-printing scaffolds show promising potential for treating bone tumors by offering sequential anti-tumor effects and bone regeneration capabilities. This work also presents a new avenue for the interface engineering of bioactive scaffolds to meet multifaceted demands in osteosarcoma-related bone defects.

Engineering ultrasound-activated piezoelectric hydrogels with antibacterial activity to promote wound healing.

The development of nanocomposite hydrogel dressings with adhesion and superior mechanical and wound infection inhibition characteristics for wound repair and skin regeneration is urgently needed for clinical applications. In this study, the adhesive piezoelectric antibacterial hydrogels with high expansibility, degradability, and adjustable rheological properties were innovatively prepared by a simple assembly process with carboxymethyl chitosan (CMCS), tannic acid (TA), carbomer (CBM), and piezoelectric FeWO4 nanorods. As an exogenous mechanical wave, ultrasound can trigger the piezoelectric effect of FeWO4 and then effectively augment the generation of reactive oxygen species, exhibiting a superior antibacterial efficiency and preventing wound infection. In vitro and in vivo results have demonstrated that piezoelectric hydrogels can accelerate full-thickness skin wound healing in bacteria-infected mice by skin regeneration, inhibiting inflammatory response, increasing collagen deposition, and promoting angiogenesis. Such a discovery provides a representative paradigm for the rational design of piezoelectric hydrogel and effectively serves antibacterial and wound dressing fields.

Oxidative Stress Amelioration of Novel Peptides Extracted from Enzymatic Hydrolysates of Chinese Pecan Cake.

Pecan (Carya cathayensis) is an important economic crop, and its hydrolyzed peptides have been evidenced to reduce the effect of oxidative stress due to their antioxidant capacity. Hence, the protocols of ultrafiltration and gel filtration chromatography were established to obtain bioactive peptides from by-products of C. cathayensis (pecan cake). As measured by DPPH/ABTS radical scavenging, the peptides with less molecular weight (MW) possess higher antioxidant capacity. PCPH-III (MW < 3 kDa) presented higher radical scavenging capacity than PCPH-II (3 kDa < MW < 10 kDa) and PCPH-I (MW > 10 kDa) measured by DPPH (IC50: 111.0 µg/ mL) and measured by ABTs (IC50: 402.9 µg/mL). The secondary structure and amino acid composition varied by their MW, in which PCPH-II contained more α-helices (26.71%) and ß-sheets (36.96%), PCPH-III contained higher ratios of ß-turns (36.87%), while the composition of different secondary of PCPH-I was even 25 ± 5.76%. The variation trend of α-helix and random experienced slightly varied from PCPH-I to PCPH-II, while significantly decreased from PCPH-II to PCPH-III. The increasing antioxidant capacity is followed by the content of proline, and PCPH-III had the highest composition (8.03%). With regard to the six peptides identified by LC-MS/MS, two of them (VYGYADK and VLFSNY) showed stronger antioxidant capacity than others. In silico molecular docking demonstrated their combining abilities with a transcription factor Kelch-like ECH-associated protein 1 (Keap1) and speculated that they inhibit oxidative stress through activating the Keap1-Nrf2-ARE pathway. Meanwhile, increased activity of SOD and CAT­antioxidant markers­were found in H2O2-induced cells. The residue of tyrosine was demonstrated to contribute the most antioxidant capacity of VYGYADK and its position affected less. This study provided a novel peptide screening and by-product utilization process that can be applied in natural product developments.

Gallic Acid Induces S and G2 Phase Arrest and Apoptosis in Human Ovarian Cancer Cells In Vitro.

Ovarian cancer (OC) is among the top gynecologic cancers in the US with a death tally of 13,940 in the past year alone. Gallic acid (GA) is a natural compound with pharmacological benefits. In this research, the role of GA on cell proliferation, cell apoptosis, cell cycle-related protein expression was explored in OC cell lines OVCAR-3 and A2780/CP70. After 24,48 and 72 h of GA treatment, the IC50 values in OVCAR-3 cells were 22.14 ± 0.45, 20.36 ± 0.18, 15.13 ± 0.53 µM, respectively and in A2780/CP70 cells IC50 values were 33.53 ± 2.64, 27.18 ± 0.22, 22.81 ± 0.56, respectively. Hoechst 33,342 DNA staining and flow cytometry results showed 20 µM GA exposure could significantly accelerate apoptosis in both OC cell lines and the total apoptotic rate increased from 5.34%(control) to 21.42% in OVCAR-3 cells and from 8.01%(control) to 17.69% in A2780/CP70 cells. Western blot analysis revealed that GA stimulated programmed OC cell death via a p53-dependent intrinsic signaling. In addition, GA arrested cell cycle at the S or G2 phase via p53-p21-Cdc2-cyclin B pathway in the same cells. In conclusion, we provide some evidence of the efficacy of GA in ovarian cancer prevention and therapy.

Polyphenols Extracted from Chinese Hickory (Carya cathayensis) Promote Apoptosis and Inhibit Proliferation through the p53-Dependent Intrinsic and HIF-1α-VEGF Pathways in Ovarian Cancer Cells.

Ovarian cancer is the second most common gynecologic cancer with an estimated 13,940 mortalities across the United States in 2020. Natural polyphenols have been shown to double the survival time of some cancer patients due to their anticancer properties. Therefore, the effect of polyphenols extracted from Chinese hickory seed skin Carya cathayensis (CHSP) on ovarian cancer was investigated in the present study. Cell viability results showed that CHSP is more effective in inhibiting ovarian cancer cells than normal ovarian cells, with the IC50 value for inhibition of cell proliferation of Ovarian cancer cells (OVCAR-3) being 10.33 ± 0.166 µg/mL for a 24 h treatment. Flow cytometry results showed that the apoptosis rate was significantly increased to 44.21% after 24 h treatment with 20 µg/mL of CHSP. Western blot analysis showed that CHSP induced apoptosis of ovarian cancer cells through a p53-dependent intrinsic pathway. Compared with control values, levels of VEGF excreted by OVCAR-3 cancer cells were reduced to 7.87% with a 40 µg/mL CHSP treatment. Consistent with our previous reports, CHSP inhibits vascular endothelial growth factor (VEGF) secretion by regulating the HIF-1α-VEGF pathway. In addition, we also found that the inhibitory effect of CHSP on ovarian cancer is related to the up-regulation of Phosphatase and tension homolog (PTEN) and down-regulation of nuclear factor kappa-B (NF-kappa B). These findings provide some evidence of the anti-ovarian cancer properties of CHSP and support the polyphenols as potential candidates for ovarian cancer adjuvant therapy.

Preparation and Properties of Polydimethylsiloxane (PDMS)/Polyethylene Glycol (PEG)-Based Amphiphilic Polyurethane Elastomers.

Amphiphilic polyurethane elastomers (APUE) were synthesized using a two-step polyaddition reaction based on the hydroxyl-terminated polydimethylsiloxane (PDMS) and polyethylene glycol (PEG) soft segments with the molecular weights (Mw's) of 2000 and 1000, respectively. The effects of the PDMS/PEG contents on the properties and structures of the APUE were investigated. It was found that the APUE possessed high elongation, moderate tensile strength, and good thermal properties. In addition, the APUE showed tunable oxygen permeability (Dk) and water vapor transmission rate (WVTR), and a similar WVTR to that of skin could be obtained for the optimized sample (APUE2). Importantly, APUE also exhibited excellent antibacterial efficacy against two kinds of bacteria along with impressive cytocompatibility. All of the results demonstrated that the synthesized APUE will hold substantial potential for biomaterial applications.