Remodeling brain pathological microenvironment to lessen cerebral ischemia injury by multifunctional injectable hydrogels.

Ischemia stroke is one of the leading causes of death and disability worldwide. Owing to the limited delivery efficiency to the brain caused by the blood-brain barrier (BBB) and off-target effects of systemic treatment, it is crucial to develop an in situ drug delivery system to improve the therapeutic effect in ischemic stroke. Briefly, we report a multifunctional in situ hydrogel delivery system for the co-delivery of reactive oxygen species (ROS)-responsive nanoparticles loaded with atorvastatin calcium (DSPE-se-se-PEG@AC NPs) and ß-nerve growth factor (NGF), which is expected to remodel pathological microenvironment for improving cerebral ischemia injury. The in vitro results exhibited the multifunctional hydrogel scavenged oxygen-glucose deprivation (OGD)-induced free radical, rescued the mitochondrial function, and maintained the survival and function of neurons, hence reducing neuronal apoptosis and neuroinflammation, consequently relieving ischemia injury in hippocampal neurons cell line (HT22). In the rat ischemia stroke model, the hydrogel significantly minified cerebral infarction by regulating inflammatory response, saving apoptotic neurons, and promoting angiogenesis and neurogenesis. Besides, the hydrogel distinctly improved the rats' neurological deficits after cerebral ischemia injury over the long-term observation. In conclusion, the in-situ hydrogel platform has demonstrated promising therapeutic effects in both in vitro and in vivo studies, indicating its potential as a new and effective therapy.

Review on chitosan-based antibacterial hydrogels: Preparation, mechanisms, and applications.

Chitosan (CS) is known for its remarkable properties, such as good biocompatibility, biodegradability, and renewability, in addition to its antibacterial and biological activities. However, as CS is insoluble in water, it displays limited antibacterial performance under neutral and physiological conditions. A viable solution to this problem is grafting chemically modified groups onto the CS framework, thereby increasing its solubility and enhancing its antibacterial effect. Herein, the antibacterial action mechanism of CS and its derivatives is reviewed, confirming the prevalent use of composite materials comprising CS and its derivatives as an antibacterial agent. Generally, the antimicrobial ability of CS-based biomaterials can be enhanced by incorporating supplementary polymers and antimicrobial agents. Research on CS-based composite biomaterials is ongoing and numerous types of biomaterials have been reported, including inorganic nanoparticles, antibacterial agents, and CS derivatives. The development of these composite materials has considerably expanded the application of CS-based antibacterial materials. This study reviews the latest progress in research regarding CS-based composite hydrogels for wound repair, tissue engineering, drug release, water purification, and three-dimensional printing applications. Finally, the summary and future outlook of CS-based antibacterial hydrogels are presented in anticipation of a broader range of applications of CS-based antibacterial hydrogels.

An injectable carrier for spatiotemporal and sequential release of therapeutic substances to treat myocardial infarction.

Myocardial infarction (MI) has become the primary cause of cardiovascular mortality, while the current treatment methods in clinical all have their shortcomings. Injectable biomaterials have emerged as a promising solution for cardiac tissue repair after MI. In this study, we designed a smart multifunctional carrier that could meet the treatment needs of different MI pathological processes by programmatically releasing different therapeutic substances. The carrier could respond to inflammatory microenvironment in the early stage of MI with rapid release of curcumin (Cur), and then sustained release recombinant humanized collagen type III (rhCol III) to treat MI. The rapid release of Cur reduced inflammation and apoptosis in the early stages, while the sustained release of rhCol III promoted angiogenesis and cardiac repair in the later stages. In vitro and in vivo results suggested that the multifunctional carrier could effectively improve cardiac function, promote the repair of infarcted tissue, and inhibit ventricular remodeling by reducing cell apoptosis and inflammation, and promoting angiogenesis in the different pathological processes of MI. Therefore, this programmed-release carrier provides a promising protocol for MI therapy.

Responsive multifunctional hydrogels emulating the chronic wounds healing cascade for skin repair.

It remains challenging to cure chronic diabetic wounds due to its' harsh microenvironment and poor tissue regeneration ability. At present, bacteria elimination, inflammatory response suppression and angiogenesis orderly render an important paradigm for chronic diabetic wound treatment. Herein, smart-responsive multifunctional hydrogels were developed to improve chronic diabetic wound healing, which could quickly respond to the acidic environment of the diabetic wound site and mediate multistage sequential delivery of silver and curcumin-loaded polydopamine nanoparticles (PDA@Ag&Cur NPs) and vascular endothelial growth factor (VEGF). PDA@Ag&Cur NPs and VEGF endowed the hydrogels with antibacterial, anti-inflammatory and angiogenesis performances, respectively. The in vitro and in vivo experiments confirmed that our multistage drug delivery hydrogels could effectively eliminate bacteria, relieve inflammatory response, and induce angiogenesis, hence accelerating the closure of chronic diabetic wounds. In conclusion, we highlighted the importance of multistage manipulation in wound healing and offered a combinatorial therapeutic strategy to sequentially deliver drugs exactly aiming at the dynamic wound healing stages.

Regeneration of infarcted hearts by myocardial infarction-responsive injectable hydrogels with combined anti-apoptosis, anti-inflammatory and pro-angiogenesis properties.

Current treatments including drug therapy, medical device implantation, and organ transplantation have considerable shortcomings for myocardial infarction (MI), such as high invasiveness, the scarce number of donor organs, easy thrombosis, immune rejection, and poor therapeutic effects. Therefore, the development of new solutions to repair infarcted hearts is urgently needed. Smart responsive injectable hydrogels have served as a good foundation in biomedical engineering, especially for cardiac regeneration. Herein, we synthesized an injectable hydrogel that responds to the inflammatory microenvironment at the site of MI to provide the drug curcumin (Cur) and tailored recombinant humanized collagen type III (rhCol III) in a controlled manner for myocardial repair. The excellent antioxidant and anti-inflammatory properties of Cur could effectively reduce the ROS level and cell apoptosis and inhibit inflammatory reactions after MI. The tailored rhCol III promoted cell proliferation, migration, and angiogenesis. The therapeutic hydrogel resulted in the rapid recovery of cardiac function after MI by elevating the expression of the cardiac markers α-actinin and CX 43. In vitro and in vivo data showed that the combined anti-apoptosis, anti-inflammatory and pro-angiogenesis treatment strategies were an auspicious tactic for the treatment of MI, and had significant clinical application value. Furthermore, the work also demonstrated the great application potential of our tailored rhCol III in promoting the repair and regeneration of infarcted hearts.

Correction: Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds.

Correction for 'Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds' by Cheng Hu et al., J. Mater. Chem. B, 2021, 9, 9684-9699, DOI: 10.1039/D1TB02170B.

Microenvironment-responsive multifunctional hydrogels with spatiotemporal sequential release of tailored recombinant human collagen type III for the rapid repair of infected chronic diabetic wounds.

Recently, the incidence of chronic diabetic wounds increases continuously, and the existing clinical treatment is less effective. Thus, it is an urgent need to solve these problems for better clinical treatment effects. Herein, we prepared a brand-new tailored recombinant human collagen type III (rhCol III) and constructed a multifunctional microenvironment-responsive hydrogel carrier based on multifunctional antibacterial nanoparticles (PDA@Ag NPs) and our tailored rhCol III. The multifunctional smart hydrogel disintegrated quickly at the chronic diabetic wound sites and achieved the programed on-demand release of different therapeutic substances. The first released PDA@Ag NPs showed great antibacterial properties against S. aureus and E. coli. They could kill bacteria rapidly, and also showed antioxidant and anti-inflammatory effects at the wound site. The subsequent release of our tailored rhCol III could promote the proliferation and migration of mouse fibroblasts and endothelial cells during the proliferation and remodeling process of wound healing. Relevant results showed that the multifunctional smart hydrogel could promote the expression levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), decrease the inflammatory response, accelerate the deposition of collagen and increase cell proliferation and angiogenesis, thereby speeding up the healing of infected chronic wounds. In a word, the hydrogel, which took into consideration the complex microenvironment at the wound site and multi-stage healing process, could achieve programmed and responsive release of different therapeutic substances to meet the treatment needs in different wound healing stages. More importantly, our work illustrated the great application potential of our brand-new rhCol III in promoting chronic wound repair and regeneration.

PEG-α-CD/AM/liposome @amoxicillin double network hydrogel wound dressing-Multiple barriers for long-term drug release.

Wound infection and poor wound healing are the major challenges of wound treatment. Antibiotic drug treatment is the effective way to inhibit wound infection. It is necessary to achieve sustained release of antibiotics to get a longer treatment for wound infection. The double network hydrogels based on liposome, polyethylene glycol (PEG), α- cyclodextrin (α-CD) and acrylamide (AM) were developed, in which liposome acts as amoxicillin repository. Because the drug would release from the multiple barriers including two cavities of liposome and α-CD, as well as polyethylene glycol -α- cyclodextrin/acrylamide (PEG-CD/AM) double network, the PEG-α-CD/AM/liposome @amoxicillin double network hydrogels could achieve sustained drug release. The drug release assay showed that the dressing could release amoxicillin continuously until 12 days, than that of 8th day for single-network hydrogel releasing. The antibacterial ratio of the hydrogel could reach above 80%. What's more, the hydrogels present adjustable mechanical strength by changing the ratio of the components. The swelling ratio proved that the hydrogel had potential ability to absorb wound exudates. The cytotoxicity test of the hydrogels demonstrated excellent biocompatibility. These results indicated that this study can provide a new thought for antibacterial wound dressing and has a broad application prospect.

Development of Antibody-Conjugated Gold and Magnetic Nanocomposites for the Colorimetric Detection of Influenza A Virus.

A novel approach for the detection of influenza virus is of paramount importance for quick diagnosis and therapy. In this study monoclonal antibody (mAb)-conjugated MNPs/AuNPs were developed to detect the H1N1 virus. MNPs and AuNPs were synthesized and loaded with mAbs. The UV-vis spectra exhibited absorbance at 528 nm. XRD revealed the presence of crystalline particles with various diffraction peaks. FTIR confirmed the occurrence of capping molecules in the synthesized NPs. NP stability was evidenced by zeta measurements. The shape and size (mean size 15 nm) of the NPs were determined using SEM and transmission electron microscopy (TEM). In this study the mAb-AuNPs produced a redshift in the absorption spectrum due to plasmon coupling. The absorption increased when H1N1 concentration increased from 0 to 5.0 ng/mL, with the detection limit being 0.05 ng/mL. The sensitivity of mAb-AuNPs was greater than that of ELISA. Since the mAb-AuNP-based colorimetric immunosensor is simple, cost-effective, and rapidly detects H1N1, it has good prospects in pharmaceuticals and clinical diagnosis.

Rapid selection of a novel GLP-1/GIP dual receptor agonist with prolonged glycemic control and weight loss in rodent animals.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists have emerged as treatment options for reversing diabetes and obesity. Here, we screened the high potency receptor-biased GLP-1R agonists via a newly designed high-throughput GLP-1R extracellular domain (ECD)-based system and demonstrated its in vitro and in vivo therapeutic characters. METHODS: Twelve 9-mer peptides (named XEL1-XEL12) which were screened from a large phage-displayed peptide library were fused to the N-terminus of GIP (3-30) to generate another twelve fusion peptides, termed XEL13-24. Using the six lysine-altered XEL17 as leading sequences, eighteen fatty chain modified fusion peptides were further assessed via in vitro GLP-1R/GIPR-based cell assay. Moreover, the acute and long-acting in vivo effects of selected candidate on diabetic db/db mice and diet-induced obesity (DIO) rats were both carefully evaluated. RESULTS: XEL17 exhibited balanced activation potency on GLP-1R/GIPR in stable cell lines, and further assessment was performed to evaluate the XEL32, a fatty chain modified XEL17 derivative. Preclinical pharmacodynamic results in diabetic db/db mice demonstrated that XEL32 held outstanding insulinotropic and glucose-lowering activities. In addition, protracted antidiabetic effects of XEL32 were also proved by the hypoglycemic test and multiple oral glucose tolerance test. Furthermore, chronic treatment of XEL32 in DIO rats exhibited outstanding beneficial effects on body weight control, fat loss, food intake control, hemoglobin A1C (HbA1C) reduction as well as the glucose tolerance. CONCLUSIONS: XEL32, as a novel GLP-1/GIP dual receptor agonist, may supply efficient glycemic control and weight loss.

Photocatalytic antibacterial agent incorporated double-network hydrogel for wound healing.

A novel antibacterial hydrogel was prepared through the addition of IT to a chitin (CT) and polyvinyl alcohol (PVA) hydrogel, creating a promising material for wound dressings. The addition of nano particles IT endowed the anti-bacterial activity of hydrogel as well as had a positive impact on the mechanical properties of the hydrogels. The structure of the prepared hydrogel dressing was characterized by FTIR, XPS, XRD, SEM and TEM. The composite hydrogel exhibited excellent anti-bacterial activity under the visible light. Cytotoxicity tests (L929 fibroblast cells) showed all samples achieving up to 80% cell viability. Furthermore, compared with conventional dressings, wound healing test revealed that CT/PVA/IT hydrogel could accelerated wound healing in vivo, wound closure rates reached 95.5% after 10 days. This study suggests that the novel hydrogel has considerable potential for applications in wound dressings.

Synthesis of cellulose-based double-network hydrogels demonstrating high strength, self-healing, and antibacterial properties.

Novel antibacterial double-network (DN) hydrogels with superior mechanical and self-healing properties are developed via the UV-initiated copolymerization of polyacrylic acid (PAA)-grafted quaternized cellulose (QCE) and polyvinyl alcohol (PVA). The QCE functioned as an antibacterial agent, resulting in excellent antibacterial capability (antibacterial rate >93%). The hydrogels are thus protected from microbial attack in natural environments, prolonging their lifetime. The PVA functioned as a physical cross-linker, resulting in superior mechanical properties. At PVA and QCE contents of 8% and 1.5%, respectively, the strain and stress at break of hydrogel were 465.37% and 1.13MPa, respectively. The hydrogel maintained good self-healing properties owing to ionic bonding between the ferric ions and carboxylic groups, and hydrogen bonding between the PVA molecules. The hydrogel was responsive to pH; its water-holding ability could be controlled by changing the pH. The material is simply prepared and used. Hydrogels with such excellent properties could be applied in various biomedical fields.

[Mechanism of Cr(VI) biosorption by flocculating yeast].

The flocculating yeast strain SPSC01 is a fusant strain of Saccharomyces cerevisiae and Schizosaccharomyces pombe. The use of SPSC01 to absorb Cr(VI) from Cr(VI) containing aqueous solution would greatly reduce the cost of post-adsorption separation, since the superior flocculating property of SPSC01 would allow easy separation of the Cr(VI)-biomass from the solution. In order to investigate the effects of flocculating proteins on Cr(VI) reduction and absorption by SPSC01, the absorption behaviors of SPSC01 and its parental strains were compared. The results showed that Cr(VI) removal rate of SPSC01 was almost the same as that of S. pombe, which also has flocculating ability, but was faster than that of S. cerevisiae, which has no flocculating ability. When the system reached equilibrium, the amount of total Cr adsorbed by S. pombe, SPSC01 and S. cerevisiae were 68.8%, 48.6% and 37.5%, respectively. This showed that flocculation was beneficial to Cr(VI) reduction and adsorption, and suggested that focculating proteins may play a role in enhancing the Cr(VI) adsorption capacity of SPSC01 and S. pombe. We investigated the mechanism of Cr(VI) adsorption by SPSC01 using chemical modification and FTIR. The results indicated that the major functional groups (amino, carboxyl and amide) of surface proteins may contribute to the absorption of Cr(VI).