Development of multifunctional chitosan-based composite film loaded with tea polyphenol nanoparticles for strawberry preservation.

Incorporating polysaccharide-based composite films with nanobiotechnology offers a new strategy for food preservation. This study initially focuses on the preparation of tea polyphenol nanoparticles (TPNP), novel and derived from natural antibacterial agents, which serve to improve stability. Afterwards chitosan-based composite films loaded with TPNP (CTN film) were developed using solution casting method. The incorporation of TPNP significantly improved the UV/water/oxygen barrier properties, mechanical properties and thermal stability, alongside notable physical properties including water contact angle (93.65 ± 0.04°), low water vapor permeability (33.72 ± 3.32 g/m2h) and oxygen permeability (0.11 ± 0.02 g/m2h), tensile strength (61.83 ± 0.70 %), and elongation at break (31.60 ± 6.12 %). The CTN film not only exhibited exceptional biodegradability and nontoxicity, but also demonstrated remarkable antimicrobial efficacy against Escherichia coli and Bacillus subtilis. Additionally, it showcased potent antioxidant activity, boasting DPPH and ABTS radical scavenging rates up to 89.25 ± 0.18 % and 93.84 ± 0.42 %. The CTN film was successfully formed on the surface of strawberries through dip-coating process and their shelf life was extended from 4 to 6 days at 20 °C without side-effect on the weight loss, harness, pH and total soluble solids, illustrating its potential for enhancing food preservation.

Biodegradable quaternized silk fibroin sponge with highly uniform pore structure for traumatic hemostasis and anti-infection.

Developing a biodegradable sponge with rapid shape recovery and potent antibacterial and coagulation properties for traumatic hemostasis and anti-infection remains challenging. Herein, we fabricated quaternized silk fibroin (SF) sponges by freeze-drying under a constant cooling rate and modification with quaternary ammonium groups. We found the constant cooling rate enabled the sponges with a highly uniform pore structure, which provided excellent self-elasticity and shape recovery. Decoration with quaternary ammonium groups enhanced blood cells adhesion, aggregation, and activation, as well as resistance to infections from Staphylococcus aureus and Escherichia coli. The SF sponge had superior hemostatic capacity to gauze and commercial gelatin sponge in different hemorrhage models. The SF sponge exhibited favorable biodegradability and biocompatibility. Moreover, The SF sponge also promoted host cell infiltration, capillary formation, and tissue ingrowth, suggesting its potential for guiding tissue regeneration. The developed SF sponge holds great application prospects for traumatic hemostasis, anti-infection, and guiding tissue regeneration.

Multifunctional gallic acid self-assembled hydrogel for alleviation of ethanol-induced acute gastric injury.

Ethanol-induced acute gastric injury is a prevalent type of digestive tract ulcer, yet conventional treatments strategies frequently encounter several limitations, such as poor bioavailability, degradation of enzymes and adverse side effects. Gallic acid (GA), a natural compound extracted from dogwood, has demonstrated potential protective effects in mitigating acute gastric injury. However, its poor stability and limited bioavailability have restricted applications in vivo. To address these issues, we report a hydrogel constructed only by gallic acid with high bioavailability for alleviation of gastric injury. Molecular dynamic simulation studies revealed that the self-assembly of GA into hydrogel was predominantly attributed to π-π and hydrogen bonds. After assembling, the GA hydrogel exhibits superior anti-oxidative stress, anti-apoptosis and anti-inflammatory properties compared with free GA. As anticipated, in vitro experiments demonstrated that GA hydrogel possessed the remarkable ability to promote the proliferation of GES-1 cells, and alleviates apoptosis and inflammation caused by ethanol. Subsequent in vivo investigation further confirmed that GA hydrogel significantly alleviated ethanol-triggered acute gastric injury. Mechanistically, GA hydrogel treatment enhanced the antioxidant capacity, reduced oxidative stress while simultaneously suppressing the secretion of pro-inflammatory cytokines and reduced the production of pro-apoptotic proteins during the process of gastric injury. Our finding suggest that this multifunctional GA hydrogel is a promising candidate for gastric injury, particularly in cases of ethanol-induced acute gastric injury.

Self-assembly of chlorogenic acid into hydrogel for accelerating wound healing.

Wound healing remains a considerable challenge due to its complex inflammatory microenvironment. Developing novel wound dressing materials with superior wound repair capabilities is highly required. However, conventional dressing hydrogels for wound healing are often limited by their complex cross-linking, high treatment costs, and drug-related side effects. In this study, we report a novel dressing hydrogel constructed only by the self-assembly of chlorogenic acid (CA). Molecular dynamic simulation studies revealed the formation of CA hydrogel was mainly through non-covalent interactions, such as π-π and hydrogen bond. Meanwhile, CA hydrogel exhibited superior self-healing, injectability, and biocompatibility properties, making it a promising candidate for wound treatment. As expected, in vitro experiments demonstrated that CA hydrogel possessed remarkable anti-inflammatory activity, and its ability to promote the generation of microvessels in HUVEC cells, as well as the promotion of microvessel formation in HUVEC cells and proliferation of HaCAT cells. Subsequent in vivo investigation further demonstrated that CA hydrogel accelerated wound healing in rats through regulating macrophage polarization. Mechanistically, the CA hydrogel treatment enhanced the closure rate, collagen deposition, and re-epithelialization while simultaneously suppressing the secretion of pro-inflammatory cytokines and increasing the production of CD31 and VEGF during the wound healing process. Our findings indicate that this multifunctional CA hydrogel is a promising candidate for wound healing, particularly in cases of impaired angiogenesis and inflammatory responses.

Tendon-inspired hybrid hydrogel based on polyvinyl alcohol and gallic acid-lysozyme for promoting wound closure and healing.

Noninvasive wound closure remains a challenge in the field of wound healing. In this study, we report the development of a cross-linked P-GL hydrogel constructed from polyvinyl alcohol (PVA) and GL (a hydrogel consisting of gallic acid and lysozyme) that effectively promotes wound closure and healing. The P-GL hydrogel exhibited a unique lamellar and tendon-like fibrous network structure, providing good thermo-sensitivity and tissue adhesiveness up to 60 MPa, as well as retaining autonomous self-healing and acid resistance capacities. In addition, the P-GL hydrogel exhibited sustained release characteristics lasting >100 h, excellent biocompatibility both in vitro and in vivo, as well as good antibacterial activity and mechanical properties. The in vivo full-thickness skin wounds model revealed the positive wound closure and healing therapeutic effects of the P-GL hydrogels were confirmed, showing a promising potential as a noninvasive wound closure and healing bio-adhesive hydrogel.

Mucoadhesive Hydrogel with Anti-gastric Acid and Sustained-Release Functions for Amelioration of DSS-Induced Ulcerative Colitis.

Mucoadhesive hydrogels with multifunctional properties such as gastric acid resistance and sustained drug release in the intestinal tract are highly desirable for the oral treatment of inflammatory bowel diseases (IBDs). Polyphenols are proven to have great efficacies compared with the first-line drugs for IBD treatments. We recently reported that gallic acid (GA) was capable of forming a hydrogel. However, this hydrogel is prone to easy degradation and poor adhesion in vivo. To tackle this problem, the current study introduced sodium alginate (SA) to form a gallic acid/sodium alginate hybrid hydrogel (GAS). As expected, the GAS hydrogel showed excellent antiacid, mucoadhesive, and sustained degradation properties in the intestinal tract. In vitro studies demonstrated that the GAS hydrogel significantly alleviated ulcerative colitis (UC) in mice. The colonic length of the GAS group (7.75 ± 0.38 cm) was significantly longer than that of the UC group (6.12 ± 0.25 cm). The disease activity index (DAI) value of the UC group was (5.5 ± 0.57), which was markedly higher than that of the GAS group (2.5 ± 0.65). The GAS hydrogel also could inhibit the expression of inflammatory cytokines, regulating macrophage polarization and improving the intestinal mucosal barrier functions. All these results indicated that the GAS hydrogel was an ideal candidate for oral treatment of UC.

Construction of double network hydrogels using agarose and gallic acid with antibacterial and anti-inflammatory properties for wound healing.

Gallic acid (GA) has attracted extensive attention due to its excellent health benefits. Our recent work demonstrated that GA could be self-assembled into hydrogels. However, the poor mechanical properties and rapid degradation of GA hydrogels presented challenges for further applications. In this study, agarose (AG), a water-soluble polysaccharide, was used with GA to develop a double network hydrogel (GA-AG). Physical and chemical tests demonstrated that the GA-AG hydrogel at ratio of 4:5 had the highest cross-linked structure, along with excellent porosity, good water retention and a swelling ratio of 9.72 %. In addition, the cross-linked network structure enabled the GA-AG hydrogel to have good mechanical properties and better viscosity than the pure GA hydrogel. The glass transition temperature of the GA-AG hydrogel increased from 59.49 °C to 65.54 °C, while its disintegration rate decreased from 99.07 % to 64.37 % within 48 h. In vitro tests showed that the GA-AG hydrogel had excellent antibacterial activity and biocompatibility. Meanwhile, we demonstrated that this double network hydrogel significantly reduced inflammation and accelerated wound healing in vivo. From the results of our study, we expect that this stable GA-AG double network hydrogel has potential applications in wound healing.

Construction of an antibacterial hydrogel based on diammonium glycyrrhizinate and gallic acid for bacterial- infected wound healing.

The current antibacterial wound dressings with antibiotic substances or metal bactericidal agents may lead to severe multidrug resistance and poor biocompatibilities. Herein, we report an inherent antibacterial hydrogel constructed by only two naturally small molecules gallic acid (GA) and diammonium glycyrrhizinate (DG) for promoting Staphylococcus aureus (S. aureus)-infected wound healing. The resultant GAD hydrogel can be fabricated by co-assembly of these two materials through simple steps. Thanks to the incorporation of GA and DG, GAD hydrogel enabled a strong mechanical performance and great self-healing property with a sustained-release of drugs into skin wounds. Moreover, the cell viability assays showed that GAD hydrogel had good cytocompatibility by promoting cell proliferation and migration. In addition, GAD hydrogel had broad antibacterial efficiency against both Gram-positive and Gram-negative bacteria. Taken together, GAD hydrogel is a promising dressing to accelerate bacterial-infected wound healing through reconstructing an intact and thick epidermis without antibiotics or cytokines.

Construction of a sustained-release hydrogel using gallic acid and lysozyme with antimicrobial properties for wound treatment.

The purpose of this study is to provide a new strategy for constructing a temperature-controlled hydrogel as a promising agent for wound healing using natural products through physical co-assembly. Herein, the temperature-controlled physically assembled hydrogel consisting of gallic acid and lysozyme (GL) could be co-assembled into a regular fibrous structure accompanied by strong blue fluorescence with three-dimensional networks at micron levels through hydrophobic interactions, π-π interactions and hydrogen bonding. This GL hydrogel has excellent temperature sensitivity and self-healing properties, as proved by cycle high-low temperature tests. In addition, it possesses stable rheological properties, great sustained release ability, and could realize the spatiotemporal delivery of gallic acid and lysozyme. Biocompatibility and antibacterial tests proved that this well-assembled GL hydrogel has no cytotoxicity but excellent antibacterial activity. Both in vitro and in vivo experiments demonstrated that the GL hydrogel has excellent anti-inflammation efficiency and promotes the healing of chronic wounds by suppressing the expression of pro-inflammatory related genes. Tests using an E. coli-infected wound model confirmed that the GL hydrogel could terminate the inflammatory phase early and ultimately promote the healing of wounds infected by E. coli. This study provides a promising strategy for the effective treatment of wounds through a physical self-assembled hydrogel.

Co-assembling of natural drug-food homologous molecule into composite hydrogel for accelerating diabetic wound healing.

Diabetic wound healing is a major clinical challenge due to its vulnerability to bacterial infection and the prolonged inflammation in the wound. Traditional dressings for the healing of diabetic wounds are often suffered from unsatisfactory efficacy and frequent dressing changes which may cause secondary damage. Therefore, it is necessary to find a wound dressing that balances material functionality, degradation, safety, and tissue regeneration. Our recent studies demonstrated that gallic acid (GA) could spontaneously form supramolecular hydrogels at a relatively high concentration. However, a single network of GA hydrogel is prone to degradation, poor adhesion, and poor swelling, and may not be suitable for wound healing dressings. In this study, a composite hydrogel (GAK) was constructed by introducing konjac glucomannan (KGM) into the gel system of gallic acid (GA) and applied to promote diabetic wound healing. The composite hydrogel (GAK) with superior surface adhesion, stability, and swelling properties than the single-network of GA hydrogel. Moreover, in vitro experiments showed that GAK hydrogel had excellent biocompatibility and exhibited antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Additionally, the GAK hydrogel could significantly accelerate angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice, reducing the expression of related inflammatory proteins interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2), and improving the wound closure rate. The findings of this study suggest that this composite hydrogel (GAK) can be an ideal dressing material for accelerating diabetic wound healing.

Self-Assembly of Naturally Small Molecules into Supramolecular Fibrillar Networks for Wound Healing.

Self-assemblies of bioactively natural compounds into supramolecular hydrogels without structural modifications are of interest to improve their sustained releases and bioavailabilities in vivo. However, it is still a formidable challenge to dig out such a naturally small molecule with a meticulous structure which can be self-assembled to form a hydrogel for biomedical applications. Here, a new hydrogel consisting only of gallic acid (GA) via π-π stacking and hydrogen bond interactions, whereas none of GA analogues can form the similar supramolecular hydrogels, is reported. This interesting phenomenon is intriguing to further investigate the potential applications of GA hydrogels in wound healing. Notably, this GA hydrogel has rod-like structures with lengths varying from 10 to 100 µm. The biocompatibility and antibacterial tests prove that this well-assembled GA hydrogel has no cytotoxicity and excellent antibacterial activities against Escherichia coli and Staphylococcus aureus. Moreover, the GA hydrogel can significantly accelerate the process of wound healing with or without bacterial infections by mediation of inflammation signaling pathways. It is believed that the current study may shed a new light on the design of a supramolecular hydrogel based on self-assemblies of naturally small molecules to improve their bioavailabilities and diversify their uses in biomedical applications.