Smart Synthetic Biomaterials for Therapeutic Applications

In the field of biomaterials, naturally-derived and synthetic polymers are utilized individually or in combination with each other, to create bio-inspired or biomimetic materials for various bioengineering applications, including drug delivery and tissue engineering. Natural polymers, such as proteins and polysaccharides, are advantageous due to low or non-toxicity, sustainable resources, innocuous byproducts, and cell-instructive properties. Synthetic polymers offer a variety of controlled chemical and physical characteristics, with enhanced mechanical properties. Together, natural and synthetic polymers provide an almost endless supply of possibilities for the development of novel, smart materials to resolve limitations of current materials, such as limited resources, toxic components and/or harsh chemical reactions. Herein is discussed the synthetic-biological material formation for cell-instructive tissue engineering and controlled drug delivery. We hypothesized that the combination of hydrogel-based scaffold and engineered nanomaterials would assist in the development or regeneration of tissue and disease treatment. Chemically-modified alginate was formed into alginate-based nanoparticles (ABNs) to direct the intracellular delivery of proteins (e.g., growth factors) and small molecular drugs (e.g., chemotherapeutics). The ABN surface was modified with cell-targeting ligands to control drug delivery to specific cells. The ABN approach to controlled drug delivery provides a platform for studying and implementing non-traditional biological pathways for disease (e.g., osteoporosis, multiple sclerosis) and cancer treatment. Through traditional organic and polymer chemistry techniques, and materials engineering approaches, a stimuli-responsive alginate-based smart hydrogel (ASH) was developed. Physical crosslinks formed based on supramolecular networks consisting of β-cyclodextrin-alginate and a tri-block amphiphilic polymer, which also provided a reversible thermo-responsiveness to the hydrogel. The hydrogel was shear-thinning, and recovered physical crosslinks, i.e., self-healed, after un-loading. The ASH biomaterials provide a platform for injectable, therapeutics for tissue regeneration and disease treatment. Indeed, various hydrogel constituents and tunable mechanical properties created cell-instructive hydrogels which promoted tissue formation

Roles of nitrate recycling ratio in the A2/O-MBBR denitrifying phosphorus removal system for high-efficient wastewater treatment: Performance comparison, nutrient mechanism and potential evaluation

The long-term effect of nitrate recycling ratios (R = 100%–500%) on the denitrifying phosphorus removal (DPR) characteristics was studied in a novel two-sludge system, which coupled Anaerobic Anoxic Oxic (A2/O) with Moving Bed Biofilm Reactor (MBBR) for simultaneous nitrogen (N) and phosphorus (P) removals. During the 220 days’ operation, effluent COD (30.87–45.15 mg/L) can meet the discharge standard completely, but N and P removals were significantly affected by the R-value, including CODintra removal efficiency (CODintra-Re: 56.09–85.98%), TN removal (TN-Re: 52.06–80.50%), anaerobic PO43− release (PO43--An: 10.66–29.02 mg/L) and oxic PO43− absorption (PO43--O: 2.22–6.26 mg/L). Meanwhile, N and P displayed close correlation with the ΔPO43−/ΔNO3- ratio of 4.20–4.41 at R = 300%–400%, resulting in the high-efficient anoxic poly-β-hydroxyalkanoates (PHA) utilization (ΔPHAA: 64.88 mgCOD/gVSS). Based on the stoichiometry methodology, at R of 300%–400%, the percentages of phosphorus accumulation organisms (PAOs) and glycogen accumulating organisms (GAOs) contributed to ΔPHAAn (ΔGlyAn) were 71.7%, 28.3% (61.3%, 38.7%) in the anaerobic stage, respectively, while N denitrification rate (NDRA: 3.91–3.93 mg N/(gVSS·h)) and P uptake rate (PURA: 3.76–3.90 mg P/(gVSS·h)) reached the peak, suggesting superior DPR performance with higher contribution of denitrifying PAOs (DPAOs) (70%) than denitrifying GAOs (DGAOs) (30%) in the anoxic stage. Microbial community analysis showed that Accumulibacter (27.66–30.01%) was more enriched than Competibacter (13.41–14.34%) and was responsible for the improved C, N, P removals and DPR characteristics. For optimizing operation, the combined effect of nitrate recycling ratio with other process parameters especially economic evaluation should be considere

HER3-targeted protein chimera forms endosomolytic capsomeres and self-assembles into stealth nucleocapsids for systemic tumor homing of RNA interference in vivo.

RNA interference represents a potent intervention for cancer treatment but requires a robust delivery agent for transporting gene-modulating molecules, such as small interfering RNAs (siRNAs). Although numerous molecular approaches for siRNA delivery are adequate in vitro, delivery to therapeutic targets in vivo is limited by payload integrity, cell targeting, efficient cell uptake, and membrane penetration. We constructed nonviral biomaterials to transport small nucleic acids to cell targets, including tumor cells, on the basis of the self-assembling and cell-penetrating activities of the adenovirus capsid penton base. Our recombinant penton base chimera contains polypeptide domains designed for noncovalent assembly with anionic molecules and tumor homing. Here, structural modeling, molecular dynamics simulations, and functional assays suggest that it forms pentameric units resembling viral capsomeres that assemble into larger capsid-like structures when combined with siRNA cargo. Pentamerization forms a barrel lined with charged residues mediating pH-responsive dissociation and exposing masked domains, providing insight on the endosomolytic mechanism. The therapeutic impact was examined on tumors expressing high levels of HER3/ErbB3 that are resistant to clinical inhibitors. Our findings suggest that our construct may utilize ligand mimicry to avoid host attack and target the siRNA to HER3+ tumors by forming multivalent capsid-like structures

Enhanced Surface Properties of the Al0.65CoCrFeNi High-Entropy Alloy via Laser Remelting

The laser remelting technique was applied to the surface modification of the Al0.65CoCrFeNi high-entropy alloy (HEA) to further advance its mechanical potential. The microstructure of the remelted layer was refined from coarse dendritic to submicron-scale basket weave compared with the as-cast substrate, resulting in a 1.8-time increase in Vickers microhardness. The nanoindentation tests indicated that the nanohardness of the remelted layer was higher than that of each phase in the substrate. Meanwhile, the remelted layer retained considerable plasticity, as evidenced by its high Wp/Wt ratio (0.763) and strain hardening exponent (0.302). Additionally, adhesive wear prevailed on the substrate, while only abrasive wear features were observed on the remelted layer. Accordingly, the average friction coefficient and the wear rate of the remelted layer were minimized by 23% and 80%, respectively, compared with the substrate. Our findings explored an industrialized method to enhance the surface properties of the Al0.65CoCrFeNi HEA and also provided some helpful references for its laser additive manufacturing

Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery

Intracellular delivery vehicles comprised of methacrylated alginate (Alg-MA) were developed for the internalization and release of doxorubicin hydrochloride (DOX). Alg-MA was synthesized via an anhydrous reaction, and a mixture of Alg-MA and DOX was formed into sub-microspheres using a water/oil emulsion. Covalently cross-linked sub-microspheres were formed via exposure to green light, in order to investigate effects of cross-linking on drug release and cell internalization, compared to traditional techniques, such as ultraviolet (UV) light irradiation. Cross-linking was performed using light exposure alone or in combination with ionic cross-linking using calcium chloride (CaCl₂). Alg-MA sub-microsphere diameters were between 88 and 617 nm, and ζ-potentials were between −20 and −37 mV. Using human lung epithelial carcinoma cells (A549) as a model, cellular internalization was confirmed using flow cytometry; different sub-microsphere formulations varied the efficiency of internalization, with UV-cross-linked sub-microspheres achieving the highest internalization percentages. While blank (nonloaded) Alg-MA submicrospheres were noncytotoxic to A549 cells, DOX-loaded sub-microspheres significantly reduced mitochondrial activity after 5 days of culture. Photo-cross-linked Alg-MA sub-microspheres may be a potential chemotherapeutic delivery system for cancer treatment

Self-Healing and Thermoresponsive Dual-Cross-Linked Alginate Hydrogels Based on Supramolecular Inclusion Complexes

β-Cyclodextrin (β-CD), with a lipophilic inner cavity and hydrophilic outer surface, interacts with a large variety of nonpolar guest molecules to form noncovalent inclusion complexes. Conjugation of β-CD onto biomacromolecules can form physically cross-linked hydrogel networks upon mixing with a guest molecule. Herein, the development and characterization of self-healing, thermoresponsive hydrogels, based on host–guest inclusion complexes between alginate-<i>graft</i>-β-CD and Pluronic F108 (poly­(ethylene glycol)-<i>b</i>-poly­(propylene glycol)-<i>b</i>-poly­(ethylene glycol)), are described. The mechanics, flow characteristics, and thermal response were contingent on the polymer concentration and the host–guest molar ratio. Transient and reversible physical cross-linking between host and guest polymers governed self-assembly, allowing flow to occur under shear stress and facilitating complete recovery of the material’s properties within a few seconds of unloading. The mechanical properties of the dual-cross-linked, multi-stimuli-responsive hydrogels were tuned as high as 30 kPa at body temperature and are advantageous for biomedical applications such as drug delivery and cell transplantation

Effects of storage on brown rice (Oryza sativa L.) metabolites, analyzed using gas chromatography and mass spectrometry

Metabolomic studies were carried out using gas chromatography and mass spectrometry (GC-MS) on Daohuaxiang variety rice (Oryza sativa L.) from the Wuchang Geographical Indication Rice Protection Area in Heilongjiang Province, to investigate the effects of storage on brown rice metabolism. The data were subjected to principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and cluster analysis using software such as SIMCA. Analysis of the samples led to the identification of a total of 160 metabolites. No significant differences were found in the amount of metabolites before and after storage. A total of 31 differential metabolites were screened, and the changes in metabolite content showed a “reverse change” overall. Storage significantly changed the content of various metabolites in rice, with fatty acids impacted most significantly. Metabolic pathway analysis revealed that fatty acid biosynthesis is a key metabolic pathway in rice storage. The degradation of brown rice quality caused by storage is closely related to the composition and content of its metabolites, and that change in lipid content significantly affects brown rice quality during storage