Polysaccharide-Derived Ice Recrystallization Inhibitors with a Modular Design: The Case of Dextran-Based Graft Polymers.

Ice recrystallization inhibitors inspired from antifreeze proteins (AFPs) are receiving increasing interest for cryobiology and other extreme environment applications. Here, we present a modular strategy to develop polysaccharide-derived biomimetics, and detailed studies were performed in the case of dextran. Poly(vinyl alcohol) (PVA) which has been termed as one of the most potent biomimetics of AFPs was grafted onto dextran via thiol-ene click chemistry (Dex-g-PVA). This demonstrated that Dex-g-PVA is effective in IRI and its activity increases with the degree of polymerization (DP) (sizes of ice crystals were 18.846 ± 1.759 and 9.700 ± 1.920 µm with DPs of 30 and 80, respectively) and fraction of PVA. By means of the dynamic ice shaping (DIS) assay, Dex-g-PVA is found to engage on the ice crystal surfaces, thus the ice affinity accounts for their IRI activity. In addition, Dex- g-PVA displayed enhanced IRI activity compared to that of equivalent PVA alone. We speculate that the hydrophilic nature of dextran would derive PVA in a stretch conformation that favors ice binding. The modular design can not only offer polysaccharides IRI activity but also favor the ice-binding behavior of PVA.

Bio-Inspired Antibacterial Hydrogel Adhesives with High Adhesion Strength.

Traditional adhesives such as cyanoacrylate glue are mostly solvent-based. They are facing the problem of insufficient adhesion to some substrates, and also from the drawback of volatilization and release of small organic molecules in the process of usage. Therefore, a novel adhesive with non-irritating, high adhesive strength, and antibacterial properties is highly required. In this study, a full physically crosslinked zwitterionic poly(betaine sulfonate methacrylate) (PSBMA) hydrogel is proposed. The physical crosslinking interactions endow the hydrogel with good self-healing properties. Furthermore, the pure physical crosslinking hydrogel can form PSBMA powder adhesive after lyophilization and return to the hydrogel state after hydration. The mechanical properties of PSBMA adhesive can be modulated via adjusting the solid content and initiator dosage. Following the cure process similar to that of snail mucus or insect exoskeletons in nature, the adhesion of the PSBMA adhesive is improved at least 100 times than its wet state. In addition, the PSBMA adhesive is easy to be removed due to the dissociation of cross-linked structures in saltwater environments. Moreover, PSBMA adhesive with antifouling properties can effectively prevent the adhesion of proteins and bacteria, which shows potential applications in the assembly of medical devices.

Zwitterionic Unimolecular Micelles with pH and Temperature Response: Enhanced In Vivo Circulation Stability and Tumor Therapeutic Efficiency.

Circulation stability in vivo and stimuli-responsiveness under a tumor microenvironment of the polymeric prodrug micellar drug delivery systems are very critical to improve the tumor therapeutic efficiency. In this study, a series of polyamidoamine (PAMAM)-graft-poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA)-block-poly(betaine sulfonate) (PSBMA) (PDS) unimolecular micelles were prepared via atom transfer radical polymerization. PAMAM served as a hydrophobic core to load the drug, the PDMAEMA segment was a middle layer to provide both thermo- and pH-sensitivity, whereas the PSMBA shell layer was used to improve the stability of the unimolecular micelles. The PDS exhibited a spherical structure with the size of 10-20 nm at pH 7.4. PDS micelles had excellent stability to resist the large volume liquid dilution. Moreover, it exhibited excellent stability in a complex biological microenvironment because of a superhigh antiprotein adhesion capacity of the PSBMA shell layer compared with PAMAM micelles. Drug release studies confirmed that the DOX can remain in the PDS micelles at pH 7.4 and 37 °C, whereas it can rapidly be released when the pH decreases to 5.0 and/or the temperature increases to 40 °C. In vitro studies suggested that the PDS drug delivery system can effectivity induce apoptosis and inhibit the proliferation of cancer cells. In vivo studies suggested that the PDS micelles prolonged the circulation time, decreased the side effects, and increased the antitumor efficacy. Therefore, the prepared PDS micelles are a potential anticancer drug delivery carrier for cancer therapy.

Ionically Conductive Hydrogel with Fast Self-Recovery and Low Residual Strain as Strain and Pressure Sensors.

Hydrogel-based sensors have attracted enormous interest due to their broad applications in wearable devices. However, existing hydrogel-based sensors cannot integrate satisfying mechanical performances with excellent conductivity to meet the requirements for practical application. Herein, an ionically conductive hydrogel with high strength, fast self-recovery, and low residual strain is constructed through a facile soaking strategy. The proposed ionically conductive double network hydrogel is achieved by combining chemically crosslinked polyacrylamide and physically crosslinked gelatin network followed by sodium citrate solution immersing. The obtained hydrogel has a tensile strength of 1.66 MPa and an elongation of 849%. The ionically conductive hydrogels can be utilized as both strain and pressure sensors with high sensitivity. Moreover, they can be used as ionic skin to monitor various human movements precisely, demonstrating their promising potential in wearable devices and flexible electronics.

[Modeling of Abdominal Wall-Cecum Injury Adhesion and the Anti-adhesion Mechanism of mXG].

OBJECTIVE: To construct the adhesion model of abdominal wall-cecum injury and explore the prevention and treatment effect of modified xyloglucan (mXG) thermosensitive hydrogel on abdominal wall-cecal injury adhesion. METHODS: SD rats were used to construct the abdominal wall-cecal injury adhesion model. Model mice were randomly divided into blank control group (Control), commercial chitosan membrane Control group (Film) and mXG thermosensitive hydrogel group (Hydrogel), each group contained 16 rats.In the Hydrogel group, 1 mL 4% (m/V) mXG solution was smeared on the wound surface of abdominal wall and the cecum, then closed the abdomen after gel was formed (3 min).In the Film group, 2 cm×3 cm chitosan anti-adhesion Film was applied onto the wound surface of the abdominal wall before abdominal closure.In the Control group, 1 mL normal saline was applied onto the wound surface of abdominal wall and the cecum before abdominal closure.On 7 and 14 d after the operation, rats'abdominal cavity was opened by surgery to examine and score the adhesion grade between the abdominal wall and the cecum, with double-blind design.Meanwhile, the adhesion tissue or wound tissue was taken and stained by HE, Masson and Van Gieson to histological evaluate the anti-adhesion effect.The expression of transforming growth factor-ß1 (TGF-ß1) and connective tissue growth factor (CTGF) was determined by immunohistochemical staining as well. Another group of 12 SD rat models were subjected to mXG thermosensitive hydrogel intervention.At the 1 and 6 weeks postoperation, rats main organs such as heart, liver, spleen, lung and kidney were taken for histological examination with HE staining for the purpose of evaluation the toxicity of mXG in vivo. RESULTS: Adhesion grade evaluation results showed that Film group rats occurred mild adhesion, Control group rats occurred severe adhesion, while in Hydrogel group hardly rats occured adhesion, and the differences were statistically significant(P < 0.05). Histological results showed that the Hydrogel group rats recovered well at 7 d after surgery.In healing wound tissue, no mutated tissue was observed, but a certain degree of inflammatory cell infiltration was still existed. At 14 d after surgery, the inflammation cells in the wound were significantly reduced, and the healing tissue containing only a small amount of collagen fibers under the neonatal mesothelial layer.But the other two groups showed different degrees of adhesion at the 7 and 14 d post surgery.Immunohistochemical staining showed that the expression of TGF-ß1 and CTGF in the Hydrogel group were both weaker than those in the other groups, and the difference was statistically significant (P < 0.05). In vivo toxicity tests did not show significant changes in the structure of the organs of mXG gel intervention rats at different time points. CONCLUSION: mXG thermosensitive hydrogel plays a good role in physical isolation during the key period of adhesion formation and effectively prevent the occurrence of cecum-abdominal adhesion.

Hybrid pectin-Fe3+/polyacrylamide double network hydrogels with excellent strength, high stiffness, superior toughness and notch-insensitivity.

The lack of sufficient mechanical properties restricts the application of polysaccharide-based hydrogels in the field of biomedicine, especially load-bearing tissue repair. Nowadays, double network (DN) hydrogels have aroused great interest through special cooperation between two contrasting networks. Inspired by this idea, here, we devised a new strategy to prepare a pectin-Fe3+/polyacrylamide hybrid DN hydrogel using a simple two-step method. The introduction of Fe3+ ions into a pectin network to produce strong reversible ionic complexation, results in excellent toughness. Under optimal conditions, our hybrid DN hydrogels possessed tensile strength as high as 0.9 MPa, corresponding to a high strain of 1300%. Besides, our hybrid DN hydrogels also exhibited superb stiffness (elastic modulus ∼ 1.46 MPa), toughness (fracture energy ∼ 3785 J m-2), and water absorption capacity (85%). Loading-unloading tests showed that the internal fracture process of the hydrogels was continuous. Owing to the reversible structure of Fe3+-pectin complexation, the hybrid DN hydrogels also showed good fatigue resistance, notch-insensitivity and recoverability. This type of polysaccharide-based hydrogel has potential to broaden the application in the load-bearing tissue repair field.

Chemically Programmed Hydrogels for Spatiotemporal Modulation of the Cardiac Pathological Microenvironment.

After myocardial infarction (MI), sustained ischemic events induce pathological microenvironments characterized by ischemia-hypoxia, oxidative stress, inflammatory responses, matrix remodeling, and fibrous scarring. Conventional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, leading to limited myocardial repair. Engineered hydrogels have a chemically programmed toolbox for minimally invasive localization of the pathological microenvironment and personalized responsive modulation over different pathological periods. Chemically programmed strategies for crosslinking interactions, interfacial binding, and topological microstructures in hydrogels enable minimally invasive implantation and in situ integration tailored to the myocardium. This enhances substance exchange and signal interactions within the infarcted microenvironment. Programmed responsive polymer networks, intelligent micro/nanoplatforms, and biological therapeutic cues contribute to the formation of microenvironment-modulated hydrogels with precise targeting, spatiotemporal control, and on-demand feedback. Therefore, this review summarizes the features of the MI microenvironment and chemically programmed schemes for hydrogels to conform, integrate, and modulate the cardiac pathological microenvironment. Chemically programmed strategies for oxygen-generating, antioxidant, anti-inflammatory, provascular, and electrointegrated hydrogels to stimulate iterative and translational cardiac tissue engineering are discussed.

Enhancing cell cryopreservation with acidic polyamino acids integrated liquid marbles.

Cryopreservation is highly desired for long-term maintenance of the viability of living biosamples, while effective cell cryopreservation still relies heavily on the addition of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS). However, the intrinsic toxicity of DMSO is still a bottleneck, which could not only cause the clinical side effect but also induce cell genetic variants. In the meantime, the addition of FBS may bring potentially the risk of pathogenic microorganism contamination. The liquid marbles (LMs), a novel biotechnology tool for cell cryopreservation, which not only have a small volume system that facilitated recovery, but the hydrophobic shell also resisted the harm to cells caused by adverse environments. Previous LM-based cell cryopreservation relied heavily on the addition of FBS. In this work, we introduced acidic polyaspartic acid and polyglutamic acid as cryoprotectants to construct LM systems. LMs could burst in an instant to facilitate and achieve ultrarapid recovery process, and the hydrophilic carboxyl groups of the cryoprotectants could form hydrogen bonds with water molecules and further inhibit ice growth/formation to protect cells from cryoinjuries. The L929 cells could be well cryopreserved by acidic polyamino acid-based LMs. This new biotechnology platform is expected to be widely used for cell cryopreservation, which has the potential to propel LMs for the preservation of various functional cells in the future.

Chronological-Programmed Black Phosphorus Hydrogel for Responsive Modulation of the Pathological Microenvironment in Myocardial Infarction.

Electroactive hydrogels have garnered extensive interest as a promising approach to myocardial tissue engineering. However, the challenges of spatiotemporal-specific modulation of individual pathological processes and achieving nontoxic bioresorption still remain. Herein, inspired by the entire postinfarct pathological processes, an injectable conductive bioresorbable black phosphorus nanosheets (BPNSs)-loaded hydrogel (BHGD) was developed via reactive oxide species (ROS)-sensitive disulfide-bridge and photomediated cross-linking reaction. Significantly, the chronologically programmed BHGD hydrogel can achieve graded modulation during the inflammatory, proliferative, and maturation phases of myocardial infarction (MI). More details, during early infarction, the BHGD hydrogel can effectively reduce ROS levels in the MI area, inhibit cellular oxidative stress damage, and promote macrophage M2 polarization, creating a favorable environment for damaged myocardium repair. Meanwhile, the ROS-responsive structure can protect BPNSs from degradation and maintain good conductivity under MI microenvironments. Therefore, the BHGD hydrogel possesses tissue-matched modulus and conductivity in the MI area, facilitating cardiomyocyte maturation and electrical signal exchange, compensating for impaired electrical signaling, and promoting vascularization in infarcted areas in the maturation phase. More importantly, all components of the hydrogel degrade into nontoxic substances without adverse effects on vital organs. Overall, the presented BPNS-loaded hydrogel offers an expandable and safe option for clinical treatment of MI.

A Single-Component Janus Zwitterionic Hydrogel Patch with a Bionic Microstructure for Postoperative Adhesion Prevention.

The development of anti-adhesion hydrogels for preventing postoperative adhesions is an ongoing challenge, particularly in achieving a balance between exceptional antifouling properties and effective in situ tissue retention. In this study, we propose a unique approach with the design of a single-component Janus zwitterionic hydrogel patch featuring a bionic microstructure. The Janus patches were prepared through free radical polymerization of sulfobetaine methacrylate with N, N'-methylenebis(2-propenamide) as the cross-linker. The incorporation of hexagonal facets separated by interconnecting grooves on one side imparts durable and reliable in situ retention capabilities to the Janus hydrogel patch when it is applied to traumatized tissues. The opposing flat surface exhibits outstanding resistance to bacteria, proteins, and cell adhesion, due to the superhydrophilicity and excellent antifouling characteristics of zwitterionic polymers. This dual functionality empowers the Janus hydrogel patch to mitigate adhesions between traumatized and surrounding tissues. The hexagonal and groove bionic microstructures facilitate rapid drainage, promoting swift contact with the tissue for increased adhesion strength, while independent hexagonal microfacets enhance the peeling energy. In an in vivo setting, Janus zwitterionic hydrogel patches with surface microstructures form mutually embedded structures with the cecum surface, minimizing the likelihood of slippage and detachment. Remarkably, in vivo experiments involving abdominal wall cecum injuries illustrate the Janus zwitterionic hydrogel patch's superior anti-adhesion effectiveness compared to commercial controls. Thus, the Janus hydrogel patch, distinguished by its bionic microstructure surface, presents substantial potential in the biomedical field for averting postoperative adhesions.

Mechanical-Enhanced and Durable Zwitterionic Hydrogel Coating for Inhibiting Coagulation and Reducing Bacterial Infection.

Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-CuII (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.

Large-Scale Fabrication of Freestanding Polymer Ultrathin Porous Membranes for Transparent Transwell Coculture Systems.

Advancements in cell coculture systems with porous membranes have facilitated the simulation of human-like in vitro microenvironments for diverse biomedical applications. However, conventional Transwell membranes face limitations in low porosity (ca. 6%) and optical opacity due to their large thickness (ca. 10 µm). In this study, we demonstrated a one-step, large-scale fabrication of freestanding polymer ultrathin porous (PUP) membranes with thicknesses of hundreds of nanometers. PUP membranes were produced by using a gap-controlled bar-coating process combined with polymer blend phase separation. They are 20 times thinner than Transwell membranes, possessing 3-fold higher porosity and exhibiting high transparency. These membranes demonstrate outstanding molecular permeability and significantly reduce the cell-cell distance, thereby facilitating efficient signal exchange pathways between cells. This research enables the establishment of a cutting-edge in vitro cell coculture system, enhancing optical transparency, and streamlining the large-scale manufacturing of porous membranes.

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.

Synthesis of agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] zwitterionic graft copolymers via ATRP and their thermally-induced aggregation behavior in aqueous media.

A novel polysaccharide-based zwitterionic copolymer, agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (agarose-g-PDMAPS) with UCST, depending both on hydrogen bonding and electrostatic interaction, was synthesized by ATRP, and its aggregation behavior in aqueous media was investigated in detail. Proton nuclear magnetic resonance spectroscopy, Fourier transform-infrared spectroscopy, and gel-permeation chromatography were performed to characterize the copolymer. Thermosensitive behaviors of the copolymers in water, NaCl, and urea solution were tracked by ultraviolet, dynamic light scattering, and transmission electron microscopy analysis. It was found that the copolymers existed as "core-shell" spheres at an elevated temperature, as a result of the self-assembly of the agarose backbones located in the "core" driven by hydrogen-bonding interactions. When the copolymer solution was cooled below UCST, the core-shell spheres began to aggregate because of the electrostatic interactions and collapse of PDMAPS side chains in the "shell" layer. UCST of the copolymer could be tuned in a wide range, depending on the chain lengths of PDMAPS. This is the first example to investigate the thermosensitivity, combining ionic interactions of the zwitterionic side chains with hydrogen bondings from the biocompatible agarose backbones. The synthetic strategy presented here can be employed in the preparation of other novel biomaterials from a variety of polysaccharides.

A self-gelling powder based on polyacrylic acid/polyacrylamide/quaternate chitosan for rapid hemostasis.

In order to improve the hemostatic effect of the hemostatic dressing for non-compressible wounds, unknown bleeding points and irregularly shaped wounds, a self-gelling hemostasis powder based on polyacrylic acid/polyacrylamide/quaternate chitosan (PAA/PAM/QCS) is prepared in this study. When in contact with water, the PAA/PAM/QCS can fuse and rapidly form a stable hydrogel in a short time (< 0.25 min). The PAA/PAM ratio is the main parameter that modulates the formation of the self-gel. The PAA/PAM self-gel can be formed only when the PAA/PAM ratio is 5:5, and the introduction of QCS does not influence the self-gelling behaviors and hydrogel stability. Moreover, the PAA/PAM/QCS self-gel shows good adhesive properties on wet tissue surfaces. In addition, the introduction of QCS improves the antibacterial activity of the self-gelling hemostasis powder. Furthermore, the prepared PAA/PAM/QCS powder can rapidly adsorb lots of blood, aggregate blood cells and platelets. The hemostatic results in vivo show that PAA/PAM/QCS powder is superior to the control group and commercial product groups (chitosan powder) with performance similar to hemostatic zeolite in terms of the amount of bleeding and hemostatic time. Therefore, the PAA/PAM/QCS self-gelling powder shows great application prospects for rapid hemostasis.

Strongly adhesive zwitterionic composite hydrogel paints for surgical sutures and blood-contacting devices.

Hydrogels show eminent advantages in biomedical and pharmaceutical fields. However, their application as coating materials for biomedical devices is limited by several key challenges, such as lack of universality, weak mechanical strength, and low adhesion to the substrate. Here we report versatile and tough adhesion composite hydrogel paints (CHPs), which consist of zwitterionic copolymers and microgels, both with reactive groups. The CHPs exhibit tunable rheology and thickness, hydrophilicity, biofouling resistance, durability, and convenient fabrication on metal, polymer, and inorganic surfaces with arbitrary shapes. As a proof-of-concept, the CHP-surgical sutures demonstrate exceptional lubrication, drug delivery, anti-infection, and anti-fibrous capsule properties. Moreover, the CHP-PVC tubing effectively prevents thrombus formation in vitro and ex vivo rabbit blood circulation without anticoagulants. This work provides valuable insights for enhancing and developing integrated hydrogel technologies for biomedical devices. STATEMENT OF SIGNIFICANCE: The combination of hydrogel and biomedical devices can enable numerous existing applications in medicine. In this study, inspired by the principle of microgel reinforcement in industrial paints, we propose a simple and versatile zwitterionic composite hydrogel paints (CHPs) strategy, which can be easily applied to diverse substrates with arbitrary shapes by covalent grafting between complementary groups by brush, dip, or spray. The CHPs integrated universality, tough adhesion, mechanical durability, and anti-biofouling properties because of their unique chemical composition and coating structure design. This strategy provides a simple and versatile route for surface modification of biomedical devices.

A biocompatible cell cryoprotectant based on sulfoxide-containing amino acids: mechanism and application.

The preservation of cells at cryogenic temperatures requires the presence of cryoprotectants (CPAs). Dimethyl sulfoxide (DMSO), as a state-of-the-art CPA, is widely used for the storage of many types of cells. However, its intrinsic toxicity is still an obstacle for its applications in clinical practice. Herein, we report a DMSO analogue, L-methionine sulfoxide (Met(O)-OH), as a CPA for cell cryopreservation. The molecular-level cryopreservation roles of Met(O)-OH were investigated by experiments and molecular dynamics simulations. The results also found that Met(O)-OH showed high ice recrystallization inhibition (IRI) activity and the ice crystals in Met(O)-OH solution tend to be relatively round and smooth; moreover, the ice size was significantly reduced to 30.26 µm compared with pure water (135.87 µm) or DMSO solution (45.08 µm). At the molecular level, Met(O)-OH could stably bind the surface of the ice crystals and form more stable hydrogen bonds with ice compared with L-methionine. Moreover, Met(O)-OH could significantly reduce the damage to cells caused by osmotic shock and did not change the cell viability even at high concentration (4%). Based on these results, nucleated L929 cells and anuclear sheep red blood cells (SRBCs) were used as cell models to investigate the cryopreservation activity of Met(O)-OH. The results suggested that, under the optimum protocol, Met(O)-OH showed an effective post-thaw survival efficiency with ultrarapid freezing, and the post-thaw survival efficiency of L929 cells reached 84.0%. This work opens up the possibility for an alternative to traditional toxic CPA DMSO, and provides insights for the development of DMSO analogues with non-toxic/low toxicity for cell cryoprotection applications.

A Zwitterionic Hydrogel with Anti-Oxidative and Anti-Inflammatory Properties for the Prevention of Peritoneal Adhesion by Inhibiting Mesothelial-Mesenchymal Transition.

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-ß). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.

Zwitterionic Polysaccharide-Based Hydrogel Dressing as a Stem Cell Carrier to Accelerate Burn Wound Healing.

Stem cell therapy integrated with hydrogels has shown promising potential in wound healing. However, the existing hydrogels usually cannot reach the desired therapeutic efficacy for burn wounds due to the inadaptability to wound shape and weak anti-infection ability. Moreover, it is difficult to improve the environment for the survival and function of stem cells under complicated wound microenvironments. In this study, an injectable and self-healing hydrogel (DSC), comprising sulfobetaine-derived dextran and carboxymethyl chitosan, is fabricated through a Schiff-base reaction. Meanwhile, the DSC hydrogel shows high nonfouling properties, including resistance to bacteria and nonspecific proteins; moreover, the prepared hydrogel can provide a biomimetic microenvironment for cell proliferation whilst maintaining the stemness of adipose-derived stem cells (ADSCs) regardless of complex microenvironments. In burnt murine animal models, the ADSCs-laden hydrogel can significantly accelerate wound healing rate and scarless skin tissue regeneration through multiple pathways. Specifically, the ADSCs-laden DSC hydrogel can avoid immune system recognition and activation and thus reduce the inflammatory response. Moreover, the ADSCs-laden DSC hydrogel can promote collagen deposition, angiogenesis, and enhance macrophage M2 polarization in the wound area. In summary, sulfobetaine-derived polysaccharide hydrogel can serve as a versatile platform for stem cell delivery to promote burn wound healing.

Injectable spontaneously formed asymmetric adhesive hydrogel with controllable removal for wound healing.

Healing large-scale wounds has been a long-standing challenge in the field of biomedicine. Herein, we propose an injectable oxidated sodium alginate/gelatin/3,3'-dithiobis(propionic hydrazide)-aurum (Alg-CHO/gelatin/DTPH-Au) hydrogel filler with asymmetric adhesion ability and removability, which is formed by the Schiff-base reaction between aldehyde-based sodium alginate and multi-amino crosslinkers (gelatin and DTPH), combined with the coordination interaction between Au nanoparticles and disulfide bond of DTPH. Consequently, the prepared Alg-CHO/gelatin/DTPH-Au hydrogel exhibits high mechanical properties and injectable behaviors owing to its multiple-crosslinked interactions. Moreover, because various types of interaction bonding form on the contact side with the tissue, denser crosslinking of the upper layer relative to the lower layer occurs. Combined with the temperature difference between the upper and lower surfaces, this results in asymmetric adhesive properties. Owing to the photothermal effect, the reversible coordination interaction between Au nanoparticles and DTPH and the change in the triple helix structure of gelatin to a coil structure impart the filler-phased removability and antibacterial ability. The choice of all natural polymers also allows for favorable degradability of the wound filler and outstanding biocompatibility. Based on these features, this versatile wound filler can achieve a wide range of applications in the field of all-skin wound repair.