Bioinspired Adhesive Antibacterial Hydrogel with Self-Healing and On-Demand Removability for Enhanced Full-Thickness Skin Wound Repair.

Adhesive-caused injury is a great threat for extensive full-thickness skin trauma because extra-strong adhesion can incur unbearable pain and exacerbate trauma upon removal. Herein, inspired by the mussel, we designed and fabricated an adhesive antibacterial hydrogel dressing based on dynamic host-guest interaction that enabled on-demand stimuli-triggered removal to effectively care for wounds. In contrast with most hard-to-removable dressing, this adhesive antibacterial hydrogel exhibited strong adhesion property (85 kPa), which could achieve painless and noninvasive on-demand separation within 2 s through a host-guest competition mechanism (amantadine). At the same time, the hydrogel exhibited rapid self-healing properties, and the broken hydrogel could be completely repaired within 5 min. The hydrogel also had excellent protein adsorption properties, mechanical properties, antibacterial properties, and biocompatibility. This on-demand removal was facilitated by the introduction of amantadine as a competitive guest, without any significant adverse effects on cell activity (>90%) or wound healing (98.5%) in vitro. The full-thickness rat-skin defect model and histomorphological evaluation showed that the hydrogel could significantly promote wound healing and reduce scar formation by regulating inflammation, accelerating skin re-epithelialization, and promoting granulation tissue formation. These results indicate that the developed adhesive antibacterial hydrogel offers a promising therapeutic strategy for the healing of extensive full-layer skin injuries.

A novel multi-scale pressure sensing hydrogel for monitoring the physiological signals of long-term bedridden patients.

For long-term bedridden patients who need to wear diapers, the timely replacement of diapers is very important to ensure their quality of life. Therefore, it is urgent to develop a pressure sensor that can monitor the physiological conditions of patients in real time. Inspired by the multi-scale network structure of the multi-fiber protein in the muscle, a multi-scale hydrogel as a pressure sensor was prepared by introducing micron-scale hydrogel microspheres as physical crosslinking agents. Compared with the traditional polyacrylamide hydrogel (0.17 MPa of compressive strength), the multi-scale hydrogel showed a higher compressive strength of up to 1.37 MPa. Meanwhile, the hydrogel exhibited better pressure sensitivity (0.59 kPa-1) than the existing hydrogels (0.27-0.40 kPa-1). The sensor prepared by this hydrogel could monitor the patient's physiological condition (urine outflow and urinary filling) in real time through the conductivity response to ion concentration and pressure, and then transmit the signal to the caregivers in time to avoid skin damage. This multi-scale hydrogel provided a great convenience for the physiological monitoring of long-term bedridden patients by acting as a pressure sensor.

A Janus supramolecular hydrogel prepared by one-pot method for wound dressing.

Despite the adhesive hydrogels have gained progress and popularity, it is still an enormous challenge to develop a smart adhesion hydrogel for clinical medicine, which is an asymmetric adhesion hydrogel with on-demand detachment. Motivated by the thermal phase transition mechanism of gelatin, we have synthesized a Janus supramolecular hydrogel dressing with skin temperature-triggered adhesion by a simple one-pot process. This hydrogel has asymmetric and controllable adhesion, which not only can become the external objects barrier but also can achieve repeated adhesion and on-demand detachment triggered by temperature in tens of seconds. This hydrogel presents great mechanical performance (compressive strain of 65 %, 1.38 MPa) owing to the presence of supramolecular interactions in the hydrogel. Additionally, this hydrogel exhibits excellent antibacterial activity and biocompatibility. The synergistic effect of modified gelatin and ionic liquid greatly facilitates wound healing of full-thickness skin with high wound healing efficiency (98.45 %). Therefore, thanks to all these advantages, the Janus supramolecular hydrogel can be applied for wound management and treatment, which has huge potential in healing skin wounds.

Difference analysis of the structure and functional properties among coix seed prolamin fractions (α-, ß-, and γ-coixin).

The differences in proteins in structural characteristics are reported to affect their physicochemical and functional properties. In this study, three types of prolamins (γ-, α-, and ß-coixin) derived from coix seed separately distributed among fractions 1-3 extracts. They were studied respecting molecular weight, amino acid composition, secondary structure, microstructure, surface hydrophobicity, solubility, water holding capacity, and oil holding capacity. Results showed that the molecular weights of those three fractions were between 10 and 40 kDa. The secondary structure of those fractions was almost the same, mainly based on ß-sheet and irregular structure. The microstructure of α- and γ-coixin presented an irregular shape, whereas ß-coixin presented a regular spherical shape. Those three fractions exhibited species of abundant essential amino acids with the same amino acid composition but different contents. The ß-coixin fraction had the highest content of hydrophobic amino acids (238.39 mg/g) followed by the α-coixin fraction (235.05 mg/g), whereas the γ-coixin fraction had the lowest content (33.27 mg/g). The γ-coixin fraction has the maximum surface hydrophobicity, whereas the ß-coixin fraction has the highest solubility. In addition, the good amphiphilicity of ß-coixin fraction made it possible to be used as a surfactant. The excellent functional properties of the ß-coixin fraction presented in this research would widen the applications of coix seed prolamins. PRACTICAL APPLICATION: The molecular weights of those three fractions were between 10 and 40 kDa. The secondary structure was almost the same, mainly based on ß-sheet and irregular structure. Those three fractions exhibited species of abundant essential amino acids with the same amino acid composition but different contents. The WHC and OHC of ß-coixin were the best, indicating its potential as a surfactant and forming stable lotion.

Modulating the performance of lipase-hydrogel microspheres in a "micro water environment".

In our previous work, we successfully stimulated lipase activity in an anhydrous reaction system using porous polyacrylamide hydrogel microsphere (PPAHM) as a carrier of lipase and free water. However, the effect of the existence state and content of water in lipase-porous polyacrylamide hydrogel microsphere (L-PPAHM) on the interfacial activation remained unclear. In this work, L-PPAHM with different water contents were obtained by water mist rehydration and were used to catalyze the synthesis of conjugated linoleic acid ethyl ester (CLA-EE). The results revealed that there were three existence states of water in L-PPAHM: bound water, semi-bound water and free water, and free water provided the "micro water environment" for the interfacial activation of lipase. The reusability of L-PPAHM with different water contents showed that the activity and stability of L-PPAHM could be achieved by varying the water content of L-PPAHM. The proportion of free water in L-PPAHM increased, and the activity of L-PPAHM increased, but the strength of hydrogen bond interaction between PPAHM and lipase weakened, resulting in the decrease of stability. L-PPAHM with 2/3 of water absorption could ensure sufficient immobilized lipase activity and stability, and its water absorption property could reduce the free water generated during esterification, thus increasing the yield of CLA-EE.

Biomass-based hydrogels with high ductility, self-adhesion and conductivity inspired by starch paste for strain sensing.

Currently, hydrogel sensors for health monitoring require external tapes, bandages or adhesives to immobilize them on the surface of human skin. However, these external fixation methods easily lead to skin allergic reactions and the decline of monitoring accuracy. A simple strategy to solve this problem is to endow hydrogel sensors with good adhesion. Inspired by the starch paste adhesion mechanism, a biomass-based hydrogel with good conductivity and high repetitive adhesion strength was prepared by introducing modified starch into polyacrylic acid hydrogel system. The properties of biomass-based hydrogels could be controlled by changing the proportion of amylose and amylopectin. The biomass-based hydrogel exhibited a variety of excellent properties, including good stretchability (1290 %), high adhesion strength (pig skin: 46.51 kPa) and conductivity (2.3 S/m). Noticeably, the repeated adhesive strength of biomass-based hydrogel did not decrease with the increase of adhesion times. The strain sensor based on the biomass-based hydrogel could accurately monitor the large-scale and small movements of the human body, and had broad application prospects in the field of flexible wearable devices.

Polyionic liquids supramolecular hydrogel with anti-swelling properties for underwater sensing.

The preparation of hydrogel-based wearable sensors for underwater application with high mechanical properties and electrical conductivity is an urgent challenge. Here, a supramolecular hydrogel based on polyionic liquids was designed and prepared for underwater sensing. The introduction of functional ionic liquid structures effectively increased the supramolecular interaction in the hydrogel network, which made the hydrogel successfully resist the interference of external water molecules. Depending on the effect of charge and hydrophobic interactions, this supramolecular hydrogel sensor exhibited high tensile (759 %), high tensile strength (0.23 MPa), high sensitivity (GF = 10.76) and extensive antibacterial properties, even in seawater environment. The obtained hydrogel sensor successfully monitored the swimming posture, which was helpful to digitally reflect the limb movement of athletes during underwater sports. This work made progress in the field of underwater wearable sensors based on hydrogels, and this design of multifunctional hydrogel provided a new idea for the development of functional sensors.

Lipase-polydopamine magnetic hydrogel microspheres for the synthesis of octenyl succinic anhydride starch.

Octenyl succinic anhydride (OSA) starch is an important edible additive in the food field, and its synthesis method has attracted much attention. Lipase as a biocatalyst can improve the synthesis efficiency of OSA starch, and significantly inhibit the occurrence of side reactions. However, free lipase has not been widely applied in the synthesis of OSA starch due to the difficulty of separation from starch and poor reusability. In this work, a promising strategy for the synthesis of OSA starch catalyzed by lipase immobilized on polydopamine magnetic hydrogel microspheres (PMHM) is reported. The prepared lipase-polydopamine magnetic hydrogel microspheres (L-PMHM) can be uniformly dispersed in starch slurry, which is conducive to the full contact between lipase and starch. L-PMHM (Km =2.6276 µmol/mL) exhibits better affinity to the substrate than free lipase (Km = 3.4301 µmol/mL). Compared with the OSA starch catalyzed by free lipase (DS = 0.0176), the degree of substitution of OSA starch catalyzed by L-PMHM is up to 0.0277 in a short reaction time. In cyclic catalysis, L-PHMM can remain about 48 % of their original activity after 20 reuses and can be quickly separated from the product. These results suggest that L-PMHM has great potential as a biocatalyst for the efficient synthesis of OSA starch.

A starch-regulated adhesive hydrogel dressing with controllable separation properties for painless dressing change.

The development of hydrogel dressings provides unprecedented opportunities for clinical medicine. However, the traditional hydrogel dressings cannot achieve controllable adhesion and separation, which often brings unbearable pain and secondary damage to patients during removal. In this work, a starch-regulated adhesive hydrogel dressing with controllable separation properties is reported. This hydrogel dressing can achieve rapid separation through the dissociation competition mechanism of polar small molecules, which will not cause any damage or discomfort to the skin or tissues, and greatly facilitate dressing replacement. The adhesive strength of the hydrogel reaches 0.06 MPa, and remains relatively stable after repeated utilization. Meanwhile, the inhibition rate of the hydrogel for E. coli, S. aureus and C. albicans is more than 99.9%. At the same time, the hydrogel also has good swelling properties, mechanical properties and biocompatibility, and exhibits a high healing efficiency (95.01 ± 3.76%) in a rat full-thickness skin defect model. This novel hydrogel dressing with controllable separation properties provides a facile and effective method for wound management and treatment, and has great promise for long-term application of wound dressings.

Pressure-sensitive antibacterial hydrogel dressing for wound monitoring in bed ridden patients.

Pressure ulcer is a common chronic injury in the bedridden population. The wound is easily subjected to secondary pressure injury due to the inconvenient mobility of patients, which greatly prolongs the hospital stay of patients and is highly prone to wound infection or other complications. It is urgent to develop a multifunctional wound dressing with pressure sensing, real-time monitoring, and wound therapy to overcome the secondary pressure injury during treatment. Here, a polyvinyl alcohol/acrylamide-ionic liquid hydrogel dressing is designed based on the antibacterial property and electrical conductivity of imidazolidine ionic liquids. Compared with existing pressure-sensing hydrogels, the hydrogel exhibits extremely high pressure sensitivity (9.19 kPa-1). Meanwhile, the good real-time responsiveness, stable signal output as well as excellent mechanical properties enable the hydrogel to monitor human movement on a large scale, and transmit the pressure status of patient wounds to nursing staff in a timely manner to avoid secondary pressure injuries. In addition, this hydrogel dressing exhibits a wide range of antibacterial activities against Gram-negative and Gram-positive bacteria as well as fungi, and has a significant therapeutic effect on full-thickness skin wounds by inhibiting wound infection, rapidly eradicating inflammation, promoting proliferation and tissue remodeling. This multifunctional hydrogel dressing opens a therapeutic and regulatory two-pronged strategy avenue through chronic wound management and pressure sensing monitoring.

Icaritin Preparation from Icariin by a Special Epimedium Flavonoid-Glycosidase from Aspergillus sp.y848 Strain.

In this study, to obtain icaritin with high pharmacological activities from icariin, which has a content ratio of over 58% in the total flavonoids of Epimedium herb, a special Epimedium flavonoid-glycosidase was produced, purified and characterized from Aspergillus sp.y848 strain. The optimal enzyme production was gained in a medium containing 5% (w/v) wheat bran extract and 0.7% (w/v) Epimedium leaf powder as the enzyme inducer, and strain culture at 30°C for 6-7 days. The molecular weight of the enzyme was approximately 73.2 kDa; the optimal pH and temperature were 5.0 and 40°C. The enzyme Km and Vmax values for icariin were 15.63 mM and 55.56 mM/h. Moreover, the enzyme hydrolyzed the 7-O-glucosides of icariin into icariside II, and finally hydrolyzed 3-O-rhamnoside of icariside II into icaritin. The enzyme also hydrolyzed 7-O-glucosides of epimedin B to sagittatoside B, and then further hydrolyzed terminal 3-O-xyloside of sagittatoside B to icarisiede II, before finally hydrolyzing 3-O-rhamnoside of icarisiede II into icaritin. The enzyme only hydrolyzed 7-O-glucoside of epimedin A or epimedin C into sagittatoside A or sagittatoside C. It is possible to prepare icaritin from the high-content icariin in Epimedium herb using this enzyme. When 2.5% icariin was reacted at 40°C for 18-20 h by the low-cost crude enzyme, 5.04 g icaritin with 98% purity was obtained from 10 g icariin. Also, the icaritin molar yield was 92.5%. Our results showed icaritin was successfully produced via cost-effective and relatively simple methods from icariin by crude enzyme. Our results should be very useful for the development of medicines from Epimedium herb.

Hydrogen-bonded lipase-hydrogel microspheres for esterification application.

Lipase is the most widely used enzyme in industry. Due to its unique "lid" structure, lipase can only show high activity at the oil-water interface, which means that water is needed in the catalytic esterification process. However, the traditional lipase catalytic system cannot effectively control "micro-water" in the esterification environment, resulting in the high content of free water, which hinders the esterification reaction and reduces the yield. In this paper, a promising strategy of esterification catalyzed by polyacrylamide hydrogel immobilized lipase is reported. The porous polyacrylamide hydrogel microspheres (PHM) prepared by inverse emulsion polymerization are used as carrier to adsorb lipase by hydrogen bonding interaction. These hydrogel microspheres provide a "micro-water environment" for lipase in the anhydrous reaction system, and further provide an oil-water interface for "interface activation" of lipase. The obtained lipase-porous polyacrylamide hydrogel microspheres (L-PHMs) exhibit higher temperature and pH stability compared with free lipase, and the optimum enzymatic activity reach 1350 U/g (pH 6, 40 °C). L-PHMs can still remain about 49% of their original activity after 20 reuses. Furthermore, L-PHMs have been successfully applied to catalyze the synthesis of conjugated linoleic acid ethyl ester. The results suggest that this immobilization method opens up a new way for the application of lipase in ester synthesis.

A ionic liquid enhanced conductive hydrogel for strain sensing applications.

Strain-sensitive and conductive hydrogels have attracted extensive research interest due to their potential applications in various fields, such as healthcare monitoring, human-machine interfaces and soft robots. However, low electrical signal transmission and poor tensile properties still limit the application of flexible sensing hydrogels in large amplitude and high frequency motion. In this study, a novel ionic liquid segmental polyelectrolyte hydrogel consisting of acrylic acid (AAc), 1-vinyl-3-butylimidazolium bromide (VBIMBr) and aluminum ion (Al3+) was prepared by molecular design and polymer synthesis. The cationic groups and amphiphilicity of ionic liquid chain segments effectively improve the tensile behavior of the polyelectrolyte hydrogel, with a maximum tensile strength of 0.16 MPa and a maximum breaking strain of 604%. The introduction of ionic liquid segments increased the current carrying concentration of polyelectrolyte hydrogel, and the conductivity reached the initial 4.8 times (12.5 S/m), which is a necessary condition for detecting various amplitude and high frequency limb movements. The flexible electronic sensor prepared by this polyelectrolyte hydrogel efficiently detects the movement of different parts of the human body stably and sensitively, even in extreme environment (-20 °C). These outstanding advantages demonstrate the great potential of this hydrogel in healthcare monitoring and wearable flexible strain sensors.

A lipase/poly (ionic liquid)-styrene microspheres/PVA composite hydrogel for esterification application.

Enzymes are particularly attractive as biocatalysts for the green synthesis of chemicals and pharmaceuticals. However, the traditional enzyme purification and separation process is complex and inefficient, which limits the wide application of enzyme catalysis. In this paper, an efficient strategy for enzyme purification and immobilization in one step is proposed. A novel poly (ionic liquid)-styrene microsphere is prepared by molecular design and synthesis for adsorbing and purifying high activity lipase from fermentation broth directly. By optimizing the surface morphologies and charge of the microspheres, the enzyme loading is significantly improved. In order to further stabilize the catalytic environment of lipase, the resulting lipase/poly (ionic liquid)-styrene microspheres are immobilized in physical crosslinking hydrogel to obtain a complex lipase catalytic system, which can be prepared into various shapes according to the requirements of catalytic environment. In the actual catalytic reaction process, this complex lipase catalytic system exhibits excellent catalytic activity (6314.69 ± 21.27 U mg-1) and good harsh environment tolerance compared with the lipase fermentation broth (1672.87 ± 36.68 U mg-1). Under the condition of cyclic catalysis, the complex lipase catalytic system shows the outstanding reusability (After 8 cycles the enzymatic activity is still higher than that of the lipase fermentation broth) and is easily separated from the products.

A novel self-healing triple physical cross-linked hydrogel for antibacterial dressing.

The poor mechanical properties of wound dressings have always been a challenge in their application as wound protective barriers. In particular, when the hydrogel dressing absorbs the tissue fluid, the mechanical properties of the hydrogel will decrease greatly due to the swelling effect. In this study, an original antibacterial hydrogel dressing was prepared by a one-step process with acrylic acid, 1-vinyl-3-butylimidazolium, COOH-modified gum arabic, and aluminium chloride. The mechanical properties of this hydrogel were improved after water absorption due to hydrophobic interactions, so the hydrogel dressing could maintain good mechanical properties after absorption of the tissue fluid. Furthermore, 1-vinyl-3-butylimidazolium as an ionic liquid was introduced into the polymer backbone of hydrogels via covalent bonds and could promote the self-healing of hydrogels by facilitating the migration of aluminum ions with charge. The obtained hydrogels showed good self-healing properties, with a strain self-healing rate of 98.2% and a stress self-healing rate of 92.3%. In addition, this hydrogel exhibited excellent antibacterial activity against E. coli, S. aureus, and C. albicans. The results of the study on rat wound closure indicated that this hydrogel effectively accelerated the healing of a full-thickness skin defect. Therefore, this novel hydrogel has a broad application prospect in the field of wound dressing.

Modulating the in vitro gastric digestion of heat-induced beta-lactoglobulin aggregates: Incorporation with polysaccharide.

Three heat-induced protein aggregates, beta-lactoglobulin fibrils (BLGF), nanoparticles (BLGN), and worm-like aggregates (BLGW) were chosen to probe the effect of disulfide bond and surface hydrophobicity on their gastric digestion behavior. Furthermore, the effect of polysaccharide (dextran sulfate sodium, DSS) on the digestion behavior of the protein aggregates was investigated. Results showed that disulfide bond had a mild restraint on the digestion extent (maximum up to 4.65%), especially when its content was below 1 mol/mol, while the surface hydrophobicity had a stronger influence (up to 8.96%), and there is definitive positive linear relationship between the surface hydrophobicity and the digestion extent. When incorporated with DSS, both the disulfide bond content and surface hydrophobicity of the aggregates decreased, consequently, and the digestion was impeded, confirming the stronger effect from the surface hydrophobicity. The digestion extent of the heat-induced protein aggregates could be modulated linearly by incorporation of polysaccharide.

Interfacial and emulsion-stabilizing properties of zein nanoparticles: differences among zein fractions (α-, ß-, and γ-zein).

According to the solubility in the binary solvent of ethanol water, zein can be classified into α-, ß-, γ-, and δ-zein, and the difference in amino acid compositions of these fractions is believed to affect their physicochemical properties and functionalities. This research comparatively analyzed main zein fractions, namely the α-zein fraction, ß-zein fraction, and γ-zein fraction, on the formation, surface adsorption, and emulsifying properties of their anti-solvent-induced particles. Results showed that all zein fractions were able to form spherical particles through an anti-solvent procedure, and formed particles possessed different surface charge and surface hydrophobicity. γ-Zein fraction particles had the biggest size and lowest surface hydrophobicity, the highest interfacial adsorption speed, and formed the strongest viscoelastic interfacial film, as analyzed through the interfacial rheology results, while ß-zein fraction particles exhibited the poorest interfacial activity. These physicochemical differences were reflected in their emulsifying properties, whereby the γ-zein fraction particle-stabilized emulsion had the maximum tolerance to salt (50, 100, and 200 mM NaCl) and pH (4.0, 7.0, and 9.0). The excellent interfacial properties of the γ-zein fraction presented in this research would afford a new strategy for the effective application of zein.

A novel hydrogel with self-healing property and bactericidal activity.

In this study, we have designed and synthesized a novel poly (4 - vinyl benzene boronic acid - co - N - vinyl pyrrolidone - co - 1 - vinyl - 3 - butylimidazolium bromide) hydrogel (VNV hydrogel) dressing with good self-healing properties and bactericidal activity. The gelation and self-healing of this hydrogel are mainly achieved by the formation of a dynamic B-O-B bond between the polymer chains, which is fractured by external forces and subsequently reformed. This self-healing mechanism is studied in detail through the molecular design of the hydrogel. The introduction of hydrophilic chemical groups can effectively improve the porous structures, water absorption and molecular migration. These properties have a positive effect on improving self-healing properties of dynamic crosslinked hydrogels. Furthermore, this VNV hydrogel dressing displays good antibacterial activity against E. coli, S. aureus, and C. albicans. The application of VNV hydrogel dressing on rat wound surface can effectively accelerate wound healing. These results indicate that this novel VNV hydrogel dressing with good self-healing properties and bactericidal activity has potential applications in wound dressings.

Novel strategy for enhancing the color intensity of ß-Carotene: Enriching onto the oil-water interface.

A novel strategy to enhance the color intensity of ß-carotene (BC), namely, "interfacial enriching", was developed in this work. As the sole emulsifier in W/O emulsion, BC particles were enriched onto the droplet surface through emulsifying process. By increasing the concentration of BC in oil phase from 1 mg/g to 5 mg/g, the average droplet size of the emulsion decreased from 92.2 ± 5.1 µm to 34.0 ± 5.4 µm. Too low (e.g. ≤ 1 mg/g) or too high (e.g. ≥25 mg/g) concentration of BC in the oil phase yielded an insufficient coverage or flocculation of the droplets. By enriching onto the interface, the color intensity of BC were enhanced apparently at the reflectance wavelength ranging from 500 nm to 700 nm, compared with that of the BC encapsulated within the emulsion droplets. This enhancement was due to the higher availability of incident light for the BC particles on the interface than that of the BC particles buried inside the droplets.

Novel Nonreleasing Antibacterial Hydrogel Dressing by a One-Pot Method.

A novel nonreleasing antibacterial hydrogel dressing with good reusability was prepared by polyethylene glycol dimethacrylate, N,N-methylene-bis-acrylamide, methyl methacrylate, 1-vinyl-3-butylimidazolium, and acrylamide. The ionic liquid of 1-vinyl-3-butylimidazolium was polymerized in the hydrogel to endow the hydrogel dressing with an antibacterial property. The successful synthesis of the hydrogel dressing was proven by FT-IR spectroscopy and energy-dispersive spectrometry. The morphology of the hydrogel was confirmed to be a porous and interconnected network structure by scanning electron microscopy. The resultant hydrogel dressing showed many desirable features, such as a good protein adsorption property and repeatable adhesiveness as well as excellent mechanical properties. Remarkably, the hydrogel dressing displayed broad antibacterial activity against bacteria Staphylococcus aureus and Escherichia coli and fungal Candida albicans. In addition, the hydrogel dressing applied locally on wounded skin of rats could effectively avoid early infection and further accelerate wound healing. The results indicated that the nonreleasing antibacterial hydrogel had potential application in wound dressing.