Acid-based Hydrogel Research Articles

Acrylic acid-based zwitterionic hydrogel for improving the flexibility and performance of supercapacitors

BackgroundAcrylic acid (AA) is cheap and easy for polymerization to anionic polymer (PAA) as hydrogel. However, the PAA hydrogel electrolyte is fragile in compressive strength due to its high intake of water. MethodsAA is neutralized for sodium acrylate (SA), which is polymerized to obtain PAA with crosslinker. PMA is copolymerized from [2-(acryloyloxy)ethyl] trimethylammonium chloride (META) and SA with crosslinker. Both PAA and PMA are confirmed by Fourier-transform infrared spectra and with 1 M Na2SO4 for Raman spectra, electrochemical impedance and dynamic mechanical analysis in comparison. Finally, PAA and PMA hydrogel electrolytes are sandwiched with carbon electrodes as supercapacitors which are bended for electrochemistry test. Significant findingsPMA hydrogel possesses more bound water than PAA hydrogel via Raman spectra analysis, and the ionic conductivity of 72.8 mS∙cm−1 in PMA hydrogel is higher than one of 60.3 mS∙cm−1 in PAA hydrogel. The toughness of PMA hydrogel is better than PAA hydrogel from dynamic mechanical analysis. For supercapacitors, the specific capacitance of PMA supercapacitor is higher than PAA supercapacitor. Furthermore, PMA hydrogel is used for supercapacitors under bending tests. Surprisingly, PMA supercapacitor for bending 90° angle still has over 90% capacitance retention in comparison to one without bending.

Development of an integrated device utilizing exosome-hyaluronic acid-based hydrogel and investigation of its osteogenic and angiogenic characteristics

Tissue engineering (TE) has been widely proposed as a potential solution to the global shortage of donor organs for transplantation. Organic and biocompatible materials have been explored as potential candidates to mimic natural extracellular matrices for regenerative applications. Biomimetic environments have been created using these materials, and hydrogels have shown promise in tissue regeneration due to their rapid gel-forming ability and excellent biocompatibility. Therefore, achieving comparisons between studies utilizing identical materials can prove arduous, as variations in material concentrations, sample preparation techniques, and laboratory conditions significantly influence the physicochemical characteristics of hydrogel systems. To ensure their promotion for clinical purposes, stable variables are crucial. In this regard, we have created an amalgamated and simplified device to assist in hydrogel-based systems using hyaluronic acid and alginate-loaded exosomes for regenerative medicine. The objective of this study is to examine the porosity, injectability, release of loaded exosomes, mechanical properties, and the rate of dissolution and degradation of well-known biomaterials, including alginate and hyaluronic acid, at different concentrations in a stable and controlled setting provided by a simplified integrated device. Furthermore, it aims to comprehensively assess their ex vivo and in vivo osteogenesis and vascularity-related metrics.

Injectable Microparticle-containing hydrogel with controlled release of bioactive molecules for facial rejuvenation

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin's components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

Conjugated Polymer Composite Nanoparticles Augmenting Photosynthesis-Based Light-Triggered Hydrogel Promotes Chronic Wound Healing.

Diabetic chronic wounds are characterized by local hypoxia, impaired angiogenesis, and bacterial infection. In situ, self-supply of dissolved oxygen combined with the elimination of bacteria is urgent and challenging for chronic nonhealing wound treatment. Herein, an oxygen-generating system named HA-L-NB/PFE@cp involving biological photosynthetic chloroplasts (cp)/conjugated polymer composite nanoparticles (PFE-1-NPs@cp) and light-triggered hyaluronic acid-based (HA-L-NB) hydrogel for promoting diabetic wound healing is introduced. Briefly, conjugated polymer nanoparticles (PFE-1-NPs) possess unique light harvesting ability, which accelerates the electron transport rates in photosystem II (PS II) by energy transfer, elevating photosynthesis beyond natural chloroplasts. The enhanced release of oxygen can greatly relieve hypoxia, promote cell migration, and favor antibacterial photodynamic therapy. Additionally, the injectable hydrogel precursors are employed as a carrier to deliver PFE-1-NPs@cp into the wound. Under light irradiation, they quickly form a gel by S-nitrosylation coupling reaction and in situ anchor on tissues through amine-aldehyde condensation. Both in vitro and in vivo assays demonstrate that the oxygen-generating system can simultaneously relieve wound hypoxia, eliminate bacteria, and promote cell migration, leading to the acceleration of wound healing. This study provides a facile approach to develop an enhanced oxygen self-sufficient system for promoting hypoxic tissue, especially diabetic wound healing.

Nanocomposite of starch, gelatin and itaconic acid-based biodegradable hydrogel and ZnO/cellulose nanofiber: A pH-sensitive sustained drug delivery vehicle

In recent years, hydrogels as drug carriers have been receiving great interest due to their ability to change their behavior in response to one or more external stimuli. However, their initial burst release profile limits their practical applications. Therefore, we prepared a bio-based hydrogel nanocomposite (HNC) using starch, itaconic acid, acrylic acid and gelatin in the presence of CNF/ZnO-based nanohybrid (ZONH) and used it to evaluate the pH-sensitive drug release properties in different pH solutions. The prepared HNCs were analyzed using various spectroscopic and microscopic techniques. The BET analysis and swelling test of the HNC indicated improved porosity and swelling capacity due to the addition of ZONH. From the drug release study, sustained drug release rate was observed at pH 4 than those at pH 7.4 and 9, indicating controlled release as well as pH responsive behavior of the HNC. Moreover, the drug released HNC was reused as a photocatalyst for dye degradation and achieved good degradation (%). The antibacterial activity of ZONH and HNC was observed against EC and SA bacterial strains from the antibacterial test. In summary, the prepared HNC can be considered as a potential sustainable DDS for biomedical applications as well as a photocatalyst for dye contaminated water treatment.

Biobased biodegradable hydrogel containing modified cellulosic nanofiber-ZnO nanohybrid as efficient metal ions removers with recyclable capacity

In the past decades, immense attention has been paid to the development of biobased hydrogel nanocomposite (HNC) to remove metal ions from wastewater owing to their high adsorption capacity, biodegradability, and reusability. In this work, we have demonstrated the fabrication of a nanohybrid using modified cellulose nanofiber and zinc oxide nanoparticles using an eco-friendly and non-toxic approach and subsequently incorporated it into a starch/itaconic acid/acrylic acid-based hydrogel matrix. The structure and morphology of the prepared nanohybrid and HNC were characterized by different spectroscopic and microscopic techniques. The resulting HNCs were employed for the removal of metal ions (Cu(II) and Fe(II)) from aqueous solution and manifested noteworthy adsorption ability. With the incorporation of 0.25 wt% nanohybrid, the HNC showed the highest water swelling capacity of 580 g/g. Besides, the incorporation of the nanohybrid enhanced the metal ion adsorption ability of the HNC, and the removal capacity of 122 and 70 mg/g was obtained for Cu(II) and Fe(II) ions, respectively. The adsorption kinetics followed the pseudo-second-order model and isotherms were found to be fitted well with the Freundlich model. Additionally, the prepared nano-structural adsorbent can be removed easily and could be used for 3 repeated purification cycles without significant loss of efficiency. Thus, this work leads to the development of nanohybrid-containing biobased HNC as a promising candidate for the removal of toxic metal ions with remarkable reusability as well as adsorption capacity.

Sulfonium-Cross-Linked Hyaluronic Acid-Based Self-Healing Hydrogel: Stimuli-Responsive Drug Carrier with Inherent Antibacterial Activity to Counteract Antibiotic-Resistant Bacteria.

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA-SS-HA-encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity reveals that HA-SS-HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics-encapsulated HA-SS-HA hydrogel can effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA can be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacteria.

Preparation and optimization of agarose or polyacrylamide/amino acid-based double network hydrogels for photocontrolled drug release

The high water content and biocompatibility of amino-acid-based supramolecular hydrogels have generated growing interest in drug delivery research. Nevertheless, the existing dominant approach of constructing such hydrogels, the exploitation of a single amino acid type, typically comes with several drawbacks such as weak mechanical properties and long gelation times, hindering their applications. Here, we design a near-infrared (NIR) light-responsive double network (DN) structure, containing amino acids and different synthetic or natural polymers, i.e., polyacrylamide, poly(N-isopropylacrylamide), agarose, or low-gelling agarose. The hydrogels displayed high mechanical strength and high drug-loading capacity. Adjusting the ratio of Fmoc-Tyr-OH/Fmoc-Tyr(Bzl)-OH or Fmoc-Phe-OH/Fmoc-Tyr(Bzl)-OH, we could drastically shorten the gelation time of the DN hydrogels at room and body temperatures. Moreover, introducing photothermal agents (graphene oxide, carbon nanotubes, molybdenum disulfide nanosheets, or indocyanine green), we equipped the hydrogels with NIR responsivity. We demonstrated the light-triggered release of the drug baclofen, which is used in severe spasticity treatment. Rheology and stability tests confirmed the positive impact of the polymers on the mechanical strength of the hydrogels, while maintaining good stability under physiological conditions. Overall, our study contributed a novel hydrogel formulation with high mechanical resistance, rapid gel formation, and efficient NIR-controlled drug release, offering new opportunities for biomedical applications.

Development of injectable hyaluronic acid-based hydrogels with antioxidant activity for the treatment of corneal neovascularization

Corneal neovascularization (CNV) is a condition that can severely adversely affect corneal transparency, culminating in visual disturbances and potential blindness. The need to manage this condition by frequently administering glucocorticoid eye drops can increase the risk of adverse side effects while reducing the odds that patients will comply with treatment regimens. Given that CNV often coincides with elevated levels of reactive oxygen species (ROS) production, in this study a sunitinib-loaded injectable antioxidant hydrogel was developed using hyaluronic acid and tannic acid. This hydrogel was effectively able to eliminate free radicals including ABTS and DPPH, normalizing intracellular ROS levels while protecting against H2O2-induced apoptosis. This sunitinib-loaded hydrogel also effectively inhibited the proliferation and tube formation activity of endothelial cells, while also inhibiting oxidative stress, inflammatory activity, and CD31 expression, thereby effectively preserving corneal transparency, promoting more rapid epithelialization, and inhibiting alkali burn-induced CNV in vivo. This sunitinib-loaded hydrogel may thus hold great promise as a novel tool for treating CNV and corneal alkali burns.

Guanosine-driven hyaluronic acid-based supramolecular hydrogels with peroxidase-like activity for chronic diabetic wound treatment

Guanosine is often used to construct supramolecular hydrogels due to its self-assembly properties, however, the high temperature and strong alkaline construction methods greatly limit its application in biomedical fields. In this work, a guanosine-driven hyaluronic acid-based supramolecular hydrogel was developed under mild condition by employing phenylboronic acid-functionalized hyaluronic acid (HA-PBA) backbone and guanosine molecules. Guanosines self-assembled into G-quartet planes under potassium ion conditions, and formed boronic ester bonds with HA-PBA, which induced rapid formation of dynamically cross-linked hydrogels. Hemin was then binding to the G-quartet plane via π-π interactions in the hydrogels, which exhibited peroxidase activity and were highly effective in killing bacteria by generating hydroxyl radicals in the presence of H2O2. Furthermore, glucose oxidase (GOx) was incorporated into the hydrogels and the HP/G@hemin@GOx hydrogels showed good antibacterial properties, modulation of wound glucose and ROS level, and good therapeutic efficacy for diabetic chronic wounds. Overall, the self-assembly of guanosine has been shown for the first time to be a feasible method for constructing natural polymer-based supramolecular hydrogels. This guanosine-driven HA-based supramolecular hydrogel can act as a potential wound dressing for chronic diabetic wound treatment. Statement of significanceChronic wound repair remains an unsolved clinical challenge. Herein, we propose to utilize phenylboronic acid-modified hyaluronic acid and guanosine to construct supramolecular gels with peroxidase activity for chronic wound treatment. The self-assembly behavior of guanosine drives the natural macromolecular backbone to form the hydrogel, and the proposed method simplifies the gelation conditions and improves its biosafety. The G-quartets formed by the self-assembly of guanosine can act as the loading site for hemin. G-quartet/hemin complex imported peroxidase activity to the hydrogels, endowing them with the ability to kill bacteria and regulate ROS levels of cells in the wound site. This guanosine-driven supramolecular hydrogel significantly increased the rate of wound healing in diabetic mice, promising a new strategy for chronic wound treatment.

In situ photo-crosslinkable hyaluronic acid-based hydrogel embedded with GHK peptide nanofibers for bioactive wound healing

A versatile hydrogel was developed for enhancing bioactive wound healing by introducing the amphiphilic GHK peptide (GHK-C16) into a photo-crosslinkable tyramine-modified hyaluronic acid (HA-Ty). GHK-C16 self-assembled into GHK nanofibers (GHK NF) in HA-Ty solution, which underwent in situ gelation after the wound area was filled with precursor solution. Blue light irradiation (460–490 nm), with riboflavin phosphate as a photoinitiator, was used to trigger crosslinking, which enhanced the stability of the highly degradable hyaluronic acid and enabled sustained release of the nanostructured GHK derivatives. The hydrogels provided a microenvironment that promoted the proliferation of dermal fibroblasts and the activation of cytokines, leading to reduced inflammation and increased collagen expression during wound healing. The complexation of Cu2+ into GHK nanofibers resulted in superior wound healing capabilities compared with non-lipidated GHK peptide with a comparable level of growth factor (EGF). Additionally, nanostructured Cu-GHK improved angiogenesis through vascular endothelial growth factor (VEGF) activation, which exerted a synergistic therapeutic effect. Furthermore, in vivo wound healing experiments revealed that the Cu-GHK NF/HA-Ty hydrogel accelerated wound healing through densely packed remodeled collagen in the dermis and promoting the growth of denser fibroblasts. HA-Ty hydrogels incorporating GHK NF also possessed improved mechanical properties and a faster wound healing rate, making them suitable for advanced bioactive wound healing applications. Statement of significanceBy combining photo-crosslinkable tyramine-modified hyaluronic acid with self-assembled Cu-GHK-C16 peptide nanofibers (Cu-GHK NF), the Cu-GHK NF/HA-Ty hydrogel offers remarkable advantages over conventional non-structured Cu-GHK for wound healing. It enhances cell proliferation, migration, and collagen remodeling—critical factors in tissue regeneration. The incorporation of GHK nanofibers complexed with copper ions imparts potent anti-inflammatory effects, promoting cytokine activation and angiogenesis during wound healing. The Cu-GHK NF/hydrogel's unique properties, including in situ photo-crosslinking, ensure high customization and potency in tissue regeneration, providing a cost-effective alternative to growth factors. In vivo experiments further validate its efficacy, demonstrating significant wound closure, collagen remodeling, and increased fibroblast density. Overall, the Cu-GHK NF/HA-Ty hydrogel represents an advanced therapeutic option for wound healing applications.

All-Natural, Robust, and pH-Responsive Glycyrrhizic Acid-Based Double Network Hydrogels for Controlled Nutrient Release.

Supramolecular hydrogels self-assembled from naturally occurring small molecules (e.g., glycyrrhizic acid, GA) are promising materials for controlled bioactive delivery due to their facile fabrication processes, excellent biocompatibility, and versatile stimuli-responsive behaviors. However, most of these natural hydrogels suffer from poor mechanical strength and processability for practical applications. In this work, through adopting a multicomponent gel approach, we developed a novel mechanically robust GA-based hydrogel with an interpenetrating double network (DN) that is composed of a Ca2+-enhanced hydrogen-bond supramolecular GA nanofibril (GN) network and a Ca2+cross-linked natural polysaccharide sodium alginate (ALG) network. Compared to the single GN network (SN) hydrogel, the GN-ALG hybrid hydrogels (GN-ALG-DN) with the hierarchical double-network structure possess excellent mechanical properties and shaping adaptation, encouraging small and large amplitude oscillatory shear (SAOS and LAOS) rheological performances, better thermal stability, higher resistance to large compression deformations, and lower swelling behaviors. Furthermore, the GN-ALG-DN hydrogels exhibit a pH-responsive and sustained release behavior of nutrients (i.e., vitamin B12, VB12), showing a faster VB12 release rate with a higher swelling ratio in an alkaline condition (pH 7.5) than in an acidic condition (pH 2.5). This is ascribed to the fact that the higher dissociation degree of carboxylic groups in GA and ALG molecules in an alkaline environment induces the erosion and looseness of the self-assembled GN network and the ionic-cross-linked ALG network, which can lead to the decomposition of the hybrid hydrogels and thereby increases the release of nutrients. Cytotoxicity tests further demonstrate the excellent biocompatibility of the GN-ALG-DN hydrogels. This study highlights the design of robust shaped and structured supramolecular hydrogels from natural herb small molecules, which can serve as solid, edible, and stimuli-responsive active cargo delivery platforms for food, biomedical, and sustainable applications.

Cellulosic wastepaper modified starch/ itaconic acid/ acrylic acid-based biodegradable hydrogel as a sustain release of NPK fertilizer vehicle for agricultural applications

In this work, wastepaper powder was used as a modifying agent for a biodegradable hydrogel composite of starch, itaconic acid, and acrylic acid. After the addition of an optimum amount of the modifying agent, the swelling ability of the hydrogel was enhanced from 503 g/g to 647 g/g. Further, the hydrogel was also used for sustained release of NPK fertilizer and subsequent effect of the fertilizer loaded hydrogel in okra seed germination was also studied. The NPK loaded-hydrogel showed good sustained-release behavior and 98 % of N, 81 % of P and 95 % of K release were observed after 20th day of incubation. Moreover, the release study was explained by using different kinetic models. In seed germination study, a higher and faster germination rate for okra seeds was observed in case of NPK loaded hydrogel compared to the control system, which was attributed to the synergistic effect of essential macronutrients (N, P, and K) and water that were inside the hydrogel. Most importantly, the hydrogel was found to be biodegradable by using soil burial method and further confirmed by FTIR and SEM analyses. Thus, this work provides an efficient way for utilization of wastepaper in the production of a biodegradable hydrogel for agricultural applications.

Acid···Amide Supramolecular Synthon for Tuning Amino Acid-Based Hydrogels' Properties.

Supramolecular hydrogels formed by the self-assembly of N-Fmoc-L-phenylalanine derivatives are gaining relevance for several applications in the materials and biomedical fields. In the challenging attempt to predict or tune their properties, we selected Fmoc-pentafluorophenylalanine (1) as a model efficient gelator, and studied its self-assembly in the presence of benzamide (2), a non-gelator able to form strong hydrogen bonding with the amino acid carboxylic group. Equimolar mixtures of 1 and 2 in organic solvents afforded a 1:1 co-crystal thanks to the formation of an acid···amide heterodimeric supramolecular synthon. The same synthon occurred in the transparent gels formed by mixing the two components in 1:1 ratio in aqueous media, as revealed by structural, spectroscopic, and thermal characterizations performed on both the co-crystal powder and the lyophilized hydrogel. These findings revealed the possibility to modulate the properties of amino acid-based hydrogels, by involving the gelator in the formation of a co-crystal. Such crystal engineering-based approach is demonstrated to be also useful for the time-delayed release of suitable bioactive molecules, when involved as hydrogel coformers.

Inflammation-Responsive Hydrogel Spray for Synergistic Prevention of Traumatic Heterotopic Ossification via Dual-Homeostatic Modulation Strategy.

Traumatic heterotopic ossification (THO) represents one of the most prominent contributors to post-traumatic joint dysfunction, which currently lacks an effective and definitive preventative approach. Inflammatory activation due to immune dyshomeostasis during the early stages of trauma is believed to be critical in initiating the THO disease process. This study proposes a dual-homeostatic modulation (DHM) strategy to synergistically prevent THO without compromising normal trauma repair by maintaining immune homeostasis and inducing stem cell homeostasis. A methacrylate-hyaluronic acid-based hydrogel spray device encapsulating a curcumin-loaded zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, CZC) nanoparticles (CZCH) is designed. Photo-crosslinked CZCH is used to form hydrogel films fleetly in periosteal soft tissues to achieve sustained curcumin and CeO2 nanoparticles release in response to acidity and reactive oxygen species (ROS) in the inflammatory microenvironment. In vitro experiments and RNA-seq results demonstrated that CZCH achieved dual-homeostatic regulation of inflammatory macrophages and stem cells through immune repolarization and enhanced efferocytosis, maintaining immune cell homeostasis and normal differentiation. These findings of the DHM strategy are also validated by establishing THO mice and rat models. In conclusion, the CZCH hydrogel spray developed based on the DHM strategy enables synergistic THO prevention, providing a reference for a standard procedure of clinical operations.

Alum-tuned hyaluronic acid-based hydrogel with immune checkpoint inhibition for immunophoto therapy of cancer

Alum-crosslinked hyaluronic acid-dopamine (HD) hydrogel containing indocyanine green (ICG) with anti-programmed cell death-1 (PD-1) antibody (Ab) administration was developed for immunophoto therapy of cancer. Alum modulates the rheological characteristics of hydrogel for enabling syringe injection, shear-thinning feature, and slower biodegradation. In addition, alum in HD-based hydrogel provided CD8+ T cell-mediated immune responses for cancer therapy. ICG in the hydrogel under near-infrared (NIR) light exposure may induce hyperthermia and generate singlet oxygen for selective cancer cell killing. HD/alum/ICG hydrogel injection with NIR laser irradiation elevated PD-1 level in CD8+ T cells. Administration of PD-1 Ab aiming at highly expressed PD-1 in T cells may amplify the anticancer efficacies of HD/alum/ICG hydrogel along with NIR laser. HD/alum/ICG hydrogel with NIR light may have both CD8+ T cell-linked immune responses and ICG-related photodynamic/photothermal effects. Additional injection of immune checkpoint inhibitor can ultimately suppress primary and distant tumor growth by combination with those therapeutic actions.

Development and preclinical evaluation of multifunctional hydrogel for precise thermal protection during thermal ablation

Image-guided thermal ablation (TA), which is less invasive, has been widely applied for treating various kinds of tumors. However, TA still poses the potential risk of thermal damage to sensitive tissue nearby. Therefore, an adjunctive thermoprotective hydrodissection technique with constant injection of 5% glucose (5% Glu) has currently been adopted for clinical application, but this may be hazardous to humans. In this study, a multifunctional hyaluronic acid-based hydrogel (HA-Dc) was developed for hydrodissection. Compared with 5% Glu (the most clinically used solution) and the previously reported F127 hydrogel, the HA-Dc hydrogel was studied in vitro in a porcine liver model and in vivo in a rabbit model and showed good injectability and better tissue retention, stability, and thermoprotective properties throughout the TA procedure. Furthermore, in the preclinical evaluation in a Macaca fascicularis (M. fascicularis) model, HA-Dc showed excellent performance in terms of stricter neuroprotection compared with 5% Glu. In addition, the HA-Dc hydrogel with good biocompatibility and controllable degradation behavior in vivo could be a promising platform for thermal protection during clinical TA procedures.

Immunomodulation by subcutaneously injected methacrylic acid-based hydrogels and tolerogenic dendritic cells in a mouse model of autoimmune diabetes

Type 1 diabetes is an autoimmune disease associated with the destruction of insulin-producing β cells. Immunotherapies are being developed to mitigate autoimmune diabetes. One promising option is the delivery of tolerogenic dendritic cells (DCs) primed with specific β-cell-associated autoantigens. These DCs can combat autoreactive cells and promote expansion of β-cell-specific regulatory immune cells, including Tregs. Tolerogenic DCs are typically injected systemically (or near target lymph nodes) in suspension, precluding control over the microenvironment surrounding tolerogenic DC interactions with the host. In this study we show that degradable, synthetic methacrylic acid (MAA)-based hydrogels are an inherently immunomodulating delivery vehicle that enhances tolerogenic DC therapy in the context of autoimmune diabetes. MAA hydrogels were found to affect the local recruitment and activation state of macrophages, DCs, T cells and other cells. Delivering tolerogenic DCs in the MAA hydrogel improved the local host response (e.g., fewer cytotoxic T cells) and enhanced peripheral Treg expansion. Non obese diabetic (NOD) mice treated with tolerogenic DCs subcutaneously injected in MAA hydrogels showed a delay in onset of autoimmune diabetes compared to control vehicles. Our findings further demonstrate the usefulness of MAA-based hydrogels as platforms for regenerative medicine in the context of type 1 diabetes.

An injectable, self-healing, and antioxidant collagen- and hyaluronic acid-based hydrogel mediated with gallic acid and dopamine for wound repair

Injectable self-healing hydrogels with antioxidation are required in wound dressings. Because oxidative damage caused by excessive reactive oxygen species (ROS) is a common issue associated with chronic non-healing wounds. Here, collagen (COL) - and hyaluronic acid (HA)-based hydrogel with antioxidant and injectable self-healing mediated with gallic acid (GA) and dopamine (DA) offers unique advantages for wound repair. The hydrogel is constructed by COL-grafted GA (CG), HA-grafted DA (HD) and γ-poly(glutamic acid) (γ–PGA) coupled with 3-aminophenylboric acid (APBA) via the dynamic boronic ester bonds. Rheological measurements and direct visual observation demonstrated the hydrogel's desirable injectability and self-healing properties. Additionally, the hydrogel exhibits tissue adhesion properties. Biocompatibility and cell migration tests showed that the hydrogel promotes cell proliferation and migration. In vitro, antioxidant and intracellular free radical scavenging assays confirmed the hydrogel's antioxidant property and ability to scavenge excess ROS. In vivo wound healing studies have demonstrated that hydrogel can promote angiogenesis, inhibit inflammation, and promote collagen fiber deposition to accelerate wound healing.

Oral colon-targeted responsive alginate/hyaluronic acid-based hydrogel propels the application of infliximab in colitis

Currently, commercialized infliximab (IFX) has rapidly propelled the clinical treatment of IBD, however, its inherent attributes, such as off-target effects and rapid metabolism, severely limit practical applications. Moreover, high doses injection of IFX can result in IBD treatment failure, which may induce other side effects. In this study, an colon microenvironment-responsive hydrogel (AL/HA hydrogel), consisting of acid-resistant sodium alginate and colon-degraded and targeted hyaluronic acid, was constructed by simple Ca2+/Zn2+ cross-linking. The ion-mediated hydrogel exhibited the protective effect of gastrointestinal tract to avoid early drug leakage, while the inflammation environments showed well-controlled drug release and significant biodegradable behaviors. Additionally, oral hydrogel exhibited long-standing enteritis areas compared with normal mice. Therefore, hydrogel-assisted enteritis treatment has great potential in IBD as an oral agent. After that, IFX was packaged in hydrogel to fabricate a facile oral antibody delivery system to treat IBD. IFX-embedded hydrogel showed remarkable therapeutic effect on IBD compared with free IFX. Surprisingly, oral hydrogel below 7 times IFX achieve the same amount of IFX-infused treatment that will further help alleviate the drawbacks of IFX. Our work elaborated on the efficacy of oral AL/HA@IFX in IBD, providing a guarantee for the future of promoted clinical transformation.