Immune-microenvironment modulatory polyurethane-hyaluronic acid hybrid hydrogel scaffolds for diabetic wound treatment.

The healing of wounds in diabetic patients is a huge challenge issue in clinical medicine due to the disordered immune. Recruiting endogenous cells to play a role in the early stage and timely reducing inflammation to promote healing in the middle or late of injuring are both prerequisites for effective treatment. Here, inspired by natural extracellular matrix, three-dimensional porous polyurethane-hyaluronic acid hybrid hydrogel scaffolds (PUHA) were prepared to repair diabetic wound through activate cell immunity by moderate foreign body reaction, provide cell adhesion growth extracellular matrix of hyaluronic acid (HA) and exhibit anti-inflammatory effect of polyurethane (PU). The interaction between PU and HA alters the compact PU hydrogel into macroporous PUHA hydrogel scaffolds with super-swelling, elastic mechanical properties, and controllable degradation, which are suitable for endogenous cells infiltration, growth and immune activation. Additionally, incorporating with RGD, PUHA hydrogel scaffolds with bioactive physicochemical features can evidently reduce the inflammation and modulate the polarization of macrophage apparently both in vitro and in vivo, mainly through downregulation of cytokine-cytokine receptor interaction genes, leading to reprogramming immune-microenvironment and rapid diabetic wound healing. This method of gathering cells initially and intervening immune-microenvironment in time provides an expected way to design biomaterials for chronic wound healing.

Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017-2018.

Background: Metabolic associated fatty liver disease (MAFLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Flavonoid is considered a promising candidate for metabolic disease prevention although few studies have explored the relationship between flavonoid intake and MAFLD. Purpose: To assess the relationship between flavonoid intake and MAFLD prevalence in the U.S. adult population. Materials and methods: The data of this cross-sectional study was obtained from National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2017-2018. Flavonoid and subclasses intake was assessed by two 24h recalls. MAFLD was diagnosed according to the consensus definitions. Multivariate logistic regression model was performed to examine the association between flavonoid intake and MAFLD with adjustments for confounders. Results: A total of 4,431 participants were included in this cross-sectional analysis. MAFLD had a weighted prevalence of 41.93% and was not associated with total flavonoid intake. A higher anthocyanin and isoflavone intake, on the other hand, was associated with a lower prevalence of MAFLD. The protective effect of higher anthocyanin intake was significant among male, Non-Hispanic White, and Non-Hispanic Asia participants. Higher isoflavone intake was associated with a lower risk of MAFLD in participants of younger (age < 50), Non-Hispanic Black, Non-Hispanic Asia, and higher HEI-2015 scores compared with the lowest quartile of isoflavone intake. Stratified analysis showed that compared with the lowest quartile of anthocyanin intake, the effect of anthocyanin intake on MAFLD varied by racial groups (P interaction = 0.02). A positive correlation existed between HDL and anthocyanidin intake (P = 0.03), whereas a negative correlation existed between FPG and isoflavone intake (P = 0.02). Conclusion: MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD.

Tough and biodegradable polyurethane-curcumin composited hydrogel with antioxidant, antibacterial and antitumor properties.

The functionalization of tough and biodegradable hydrogels is an important way to broaden their applications in biomedical field. However, most of the hydrophobic functional drugs are difficult to incorporate with the hydrogels. In this work, curcumin (Cur), a hydrophobic functional drug, was chosen to composite with polyurethane (PU) to obtain PU-Cur hydrogels by a direct and simple in-situ copolymerization. The incorporation of curcumin in PU hydrogel increases the crosslink but reduces the hydrophilicity and degradation rate of PU-Cur hydrogels. Thus, it can increase the mechanical strength to a maximum of 6.4±0.8 MPa and initial modulus to a maximum of 3.0±0.4 MPa. More importantly, curcumin incorporated in PU networks is not deactivated. The degradation products of PU-Curs at relatively low concentrations (2.5 mg/mL) can scavenge free radicals very efficiently (maximum over 90%), which exhibits strong antioxidant properties to improve wound healing. Moreover, based on the photochemical activity of curcumin, notable inhibition effects of the degradation products of PU-Curs against bacteria (maximum over 80%) and cancer cells are demonstrated with blue light treatment as a photodynamic therapy (PDT). Therefore, the beneficial effects of curcumin are retained in PU-Cur hydrogels, suggesting potential use as wound dressings or tumor isolation membranes. This work proposes a promising strategy to combine hydrophobic functional drugs with hydrophilic hydrogels for applications in a wide range of biomaterials.

An injectable hydrogel with pH-sensitive and self-healing properties based on 4armPEGDA and N-carboxyethyl chitosan for local treatment of hepatocellular carcinoma.

Injectable hydrogels with pH-sensitive and self-healing properties have great application potential in the field of anti-cancer drug carriers. In this work, an injectable hydrogel is prepared using 4armPEG-benzaldehyde (4armPEGDA) and N-carboxyethyl chitosan (CEC) as a new drug carrier. The gelation time, equilibrium swelling rate, degradation time, and dynamic modulus of the injectable hydrogels can be adjusted by merely changing the concentration of 4armPEGDA. The volume of the hydrogel shrinks at pH 5.6 and expands at pH 7.4, which helps to control the release of anti-cancer drug. At pH 5.6, the hydrogels show a fast and substantial Dox release effect, which is five times higher than that at pH 7.4. In vitro cumulative drug release of all the hydrogels reached equilibrium on about the fourth day, and the hydrogel is completely degraded within five days, which contributes to the Dox-loaded hydrogel to further release the remaining Dox. Moreover, the Dox-loaded hydrogel shows a strong inhibitory effect on the growth of human hepatocellular carcinoma cells (HepG2). Finally, the anti-tumor model experiment in vivo demonstrated that the Dox-loaded hydrogel can significantly inhibit tumor growth within five days. Therefore, such injectable hydrogels are excellent carriers for the potential treatment of hepatocellular carcinoma.

Anti-biofilm surfaces from mixed dopamine-modified polymer brushes: synergistic role of cationic and zwitterionic chains to resist staphyloccocus aureus.

Infections resulting from the attachment of bacteria and biofilm formation on the surface of medical implants give rise to a severe problem for medical device safety. Thus, the development of antibacterial materials that integrate bactericidal and antifouling properties is a promising approach to prevent biomaterial-associated infections. In this study, two types of dopamine-modified polymers, dopamine-terminated quaternary ammonium salt polymer (D-PQAs) with various lengths of N-alkyl chain (D-PQA4C, D-PQA8C, and D-PQA12C) and dopamine-terminated poly(sulfobetaine methacrylate) (D-PSBMA), were synthesized via atom transfer radical polymerization (ATRP). Mixed polymer brushes of D-PQAs and D-PSBMA with various ratios were well-integrated onto the surface of a silicon wafer via a facile mussel-inspired adhesion. We demonstrate that the synergistic antibacterial effect depends on both the ratio of the two components and the surface structures of the mixed polymer brushes, originating from the interactions between D-PQAs and D-PSBMA. The N-alkyl chain length of D-PQAs influenced the distribution and orientation of the alkyl chain on the mixed polymer brushes. A chart of the antibacterial efficiency of the mixed polymer brushes was obtained to reveal the synergistic role of their cationic and zwitterionic chains to resist S. aureus. The dominant amount of antifouling D-PSBMA with a minor amount of bactericidal D-PQAs with a short N-alkyl chain length facilitated the synergistic antibacterial effect. The selected polymer brushes (PSBMA/PQA4C-10%, PSBMA/PQA4C-30%, and PSBMA/PQA8C-10%) could effectively prevent biofilm formation by S. aureus for a long time, while having good biocompatibility. This work may provide a universal design strategy for the preparation of anti-biofilm and biocompatible surfaces for biomedical applications.

Biodegradable, anti-adhesive and tough polyurethane hydrogels crosslinked by triol crosslinkers.

The mechanical and biodegradable properties of hydrogels are two essential properties for practical biomaterial applications. In this work, a series of biodegradable polyurethane (PU) hydrogels were successfully synthesized using two kinds of triol crosslinkers with different chain structures. One crosslinker is normal glycerol (GC) with short chain length, and the other is biodegradable poly (ε-caprolactone)-triol (CAPA) with long chain length. All PU hydrogels showed considerable water uptake around ~60%, excellent strength (above 3 MPa), advisable modulus (0.9~1.7 MPa), high elasticity (above 700%), as well as good biodegradability and biocompatibility. Hydrogen bonds served as reversible sacrificial bonds in the PU hydrogels endow them good toughness with partial hysteresis during deformation. The biodegradable long chain crosslinker CAPA can certainly accelerate the degradation of PU hydrogels compared with the GC crosslinked hydrogels. The degradation of these hydrogels was a process of continuous erosion from the surface to interior, which contributes to the high remain of mechanical properties after 30 days-degradation. Besides, the hydrogels also show excellent antifouling ability of protein and anti-adhesion of cells. Therefore, these hydrogels suggest great potential used as biological anti-adhesive membranes or catheters.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.