Hydrogel Platform Research Articles

Acid-Triggered Dual-Functional Hydrogel Platform for Enhanced Bone Regeneration.

Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant cell transformation should not be ignored. Compared to stem cell implantation, recruitment of endogenous stem cells to injured sites is more critical for in situ bone regeneration. In this study, based on the acidic microenvironment of bone injury, an HG-AA1:1-SDF-1α composite hydrogel with a dual-control intelligent switch function is developed by incorporating stromal cell-derived factor (SDF-1α), arginine carbon dots (Arg-CDs), and calcium ions (Ca2+) into the oxidized hyaluronic acid/gelatin methacryloyl (HG) hydrogel. The acidic microenvironment triggers the first switch (Schiff base bond is broken between HG-AA1:1 and SDF-1α) of HG-AA1:1-SDF-1α composite hydrogel to continuously release SDF-1α. Compared to the neutral (pH 7.4) media, the cumulative release of SDF-1α in acidic (pH 5.5) media is ≈2.5 times higher, which enhances the migration and recruitment of endogenous mesenchymal stem cells (MSCs). The recruited MSCs immediately initiate the second switch and metabolize Arg-CDs into the bioactive nitric oxide (NO) in the presence of Ca2+, activating NO/cyclic guanosine monophosphate (cGMP) signaling pathway to promote angiogenesis. Therefore, the engineered HG-AA1:1-SDF-1α composite hydrogel shows promising potential to achieve "coupling osteogenesis and angiogenesis" for bone regeneration.

Bioinspired Adhesive Hydrogel Platform with Photothermal Antimicrobial, Antioxidant, and Angiogenic Properties for Whole-Process Management of Diabetic Wounds.

Diabetic wound healing remains a major challenge in modern medicine. The persistent inflammation and immune dysfunction hinder angiogenesis by producing excessive ROS and increasing the susceptibility to bacterial infection. In this study, we developed an integrated strategy for whole-process management of diabetic wounds based on a bioinspired adhesive hydrogel platform with hemostasis, photothermal antimicrobial, antioxidant, anti-inflammatory, and angiogenic properties. A composite hydrogel (termed AQTGF) using poly(acrylic acid) (PAA) and quaternized chitosan (QCS) as the backbone materials and loaded with a TA-Gd/Fe-bimetallic-phenolic coordination polymer was prepared. The AQTGF hydrogel displayed favorable mechanical properties, self-healing capabilities, adhesion characteristics, and photothermal response performance. In vitro experiments demonstrated that the AQTGF hydrogel exhibits excellent photothermal antimicrobial capacity and antioxidant, angiogenic, and M2 macrophage phenotype polarizing properties. In addition, the rat tail amputation and liver hemostasis experiments demonstrated that the AQTGF hydrogel had excellent hemostasis performance. Moreover, in vivo studies have indicated that AQTGF hydrogel can facilitate diabetic wound healing by accelerating epidermal growth, promoting collagen deposition, modulating macrophage M2 polarization, inhibiting inflammation, and promoting angiogenesis. In conclusion, this study provides an adaptable hydrogel that holds promise for the treatment of chronic diabetic wounds.

Genetically Programmed Single-Component Protein Hydrogel for Spinal Cord Injury Repair.

Protein self-assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single-component self-assembling hydrogel is developed using the recombinant protein CsgA, and its successful application for spinal cord injury repair is demonstrated. Gelation is achieved by the physical entanglement of CsgA nanofibrils, resulting in a self-supporting hydrogel at low concentrations (≥5mg mL-1). By leveraging the programmability of the CsgA gene sequence, the bioactive hydrogel is enhanced by fusing functional peptide GHK. GHK is recognized for its anti-inflammatory, antioxidant, and neurotrophic factor-stimulating properties, making it a valuable addition to the hydrogel for spinal cord injury repair applications. In vitro experiments demonstrate that the CsgA-GHK hydrogel can modulate microglial M2 polarization, promote neuronal differentiation of neural stem cells, and inhibit astrocyte differentiation. Additionally, the hydrogel shows efficacy in alleviating inflammation and promotes neuronal regeneration at the injury site, leading to significant functional recovery in a rat model with compression injury spinal cord cavity. These findings lay the groundwork for developing a modular design platform for recombinant CsgA protein hydrogels in tissue repair applications.

Smartphone-assisted hydrogel sensing platform based on double emission carbon dots for portable on-site tetracycline detection.

Innovative double-emission carbon dots (DE-CDs) were synthesized via a one-step hydrothermal method using fennel and m-phenylenediamine (m-PD) as precursors. These DE-CDs exhibited dual emission wavelengths at 432 and 515nm under different excitations, making them highly versatile for fluorescence-based applications. The fluorescence of the DE-CDs was efficiently quenched by tetracycline (TC) through the inner filter effect (IFE), allowing for the construction of a sensitive dual-response fluorescent sensor. This sensor demonstrated a strong exponential correlation with TC concentrations in the range 0.99-118μM, achieving a low detection limit of 53.4nM, which is appropriate for environmental monitoring. To further enhance its practicality, a smartphone-integrated fluorescent hydrogel film sensing platform was developed. This portable and user-friendly system enabled rapid, on-site TC detection in water samples, combining high sensitivity with convenience for real-world applications. The integration of the DE-CD-based sensor into a hydrogel platform addressed the challenge of translating laboratory precision into field-ready tools. This study revealed the potential of DE-CDs as a robust and efficient solution for bridging the gap between laboratory-based analysis and portable, on-site environmental monitoring.

ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

ZnCur nanoparticle-enhanced multifunctional hydrogel platform: Synergistic antibacterial and immunoregulatory effects for infected diabetic wound healing

In English

In recent years, significant progress has been made in both the synthesis of metal nanoparticles and the creation of hydrogel platforms. It is assumed that their synergistic combination will allow to create the advanced hydrogel nanocomposites for the repair of anatomical and functional disorders of the human body, as well as for the needs of reconstructive surgery. The aim of the study is to develop a porous polymeric material based on polyvinylformal with incorporated functional hydrogels and gold nanoparticles, the study of its physicochemical properties and biocompatibility in vitro and in vivo. The developed hybrid hydrogel material is intended for use in reconstructive surgery of the oculo-orbital area and for filling postoperative cavities with simultaneous prevention of recurrence. The morphology of the synthesized hybrid hydrogel composites with gold nanoparticles was investigated by means of electron microscopy (SEM), while their thermal stability was studied by TGA and DSC methods. It was proved that the synthesized hybrid hydrogel materials demonstrate thermal stability in a wide temperature range, which significantly exceeds the range of their application, and can withstand steam sterilization (121 °C) without significant changes. The synthesized hybrid hydrogels were characterized as biocompatible in vitro according to the parameters of cytotoxicity, genotoxicity and biochemical markers (ATPase and LDHase activity) using L929 cell line. The study of the soft tissue reaction to implantation in vivo demonstrated the formation of fibrous tissue on the periphery and inside the implant, and a marked decrease in macrophage-histiocyte reaction and inflammatory infiltration in favor of fibroblastic proliferation and the absence of resorption, which creates the prerequisites for a stable clinical result. Thus, the developed spongy hybrid hydrogel material can be used in reconstructive surgery of the maxillofacial and ophthalmic-orbital areas.

Electroconductive Nanocellulose, a Versatile Hydrogel Platform: From Preparation to Biomedical Engineering Applications.

Nanocelluloses have garnered significant attention recently in the attempt to create sustainable, improved functional materials. Nanocellulose possesses wide varieties, including rod-shaped crystalline cellulose nanocrystals and elongated cellulose nanofibers, also known as microfibrillated cellulose. In recent times, nanocellulose has sparked research into a wide range of biomedical applications, which vary from developing 3D printed hydrogel to preparing structures with tunable characteristics. Owing to its multifunctional properties, different categories of nanocellulose, such as cellulose nanocrystals, cellulose nanofibers, and bacterial nanocellulose, as well as their unique properties are discussed here. Here, different methods of nanocellulose-based hydrogel preparation are covered, which include 3D printing and crosslinking methods. Subsequently, advanced nanocellulose-hydrogels addressing conductivity, shape memory, adhesion, and structural color are highlighted. Finally, the application of nanocellulose-based hydrogel in biomedical applications is explored here. In summary, numerous perspectives on novel approaches based on nanocellulose-based research are presented here.

Ultrastretchable and highly sensitive ionic conductive hydrogel for environmentally resistant all-in-one human-motion sensors.

Conductive hydrogels have been considered ideal candidate materials for fabricating human-motion sensors due to their combination properties of electronic and tissue-like soft nature and the similar functions of human skin with mechanical and sensory properties. However, the perfect integration of multiple functionalities such as environmentally tolerant, stretchable, self-adhesive, self-healing, transparent, high sensitivity, and rapid response in one system (all-in-one) is still a significant challenge. Herein, a novel ionic conductive hydrogel platform with excellent comprehensive performance through multiple dynamic interactions was prepared by employing [BMIm]BF4/glycerol/water ternary solvent system. The dynamic hydrogen bonds, coordination bonds, and electrostatic interaction within the network endows the hydrogel excellent mechanical performance. The synchronous effect of ionic liquids and glycerol realized the high ionic conductivity, transparency, environmentally tolerance, and long-term stability. Sensors based on this hydrogel have a relatively high sensitivity, a fast response time, and a wide linear sensing range in monitoring human movements. It can also serve as electronic skin, like human skin, for touchscreen pen and writing. Thus, the all-in-one hydrogel was concluded to hold considerable promise for constructing the next generation of hydrogel platforms for human-motion sensors.

Interpenetrating Polymer Network Hydrogels with Tunable Viscoelasticity and Proteolytic Cleavability to Direct Stem Cells In Vitro.

The dynamic nature of cellular microenvironments, regulated by the viscoelasticity and enzymatic cleavage of the extracellular matrix, remains challenging to emulate in engineered synthetic biomaterials. To address this, a novel platform of cell-instructive hydrogels is introduced, composed of two concurrently forming interpenetrating polymer networks (IPNs). These IPNs consist of the same basic building blocks - four-armed poly(ethylene glycol) and the sulfated glycosaminoglycan (sGAG) heparin - are cross-linked through either chemical or physical interactions, allowing for precise and selective tuning of the hydrogel's stiffness, viscoelasticity, and proteolytic cleavability. The studies of the individual and combined effects of these parameters on stem cell behavior revealed that human mesenchymal stem cells exhibited increased spreading and Yes-associated protein transcriptional activity in more viscoelastic and cleavable sGAG-IPN hydrogels. Furthermore, human induced pluripotent stem cell (iPSC) cysts displayed enhanced lumen formation, growth, and pluripotency maintenance when cultured in sGAG-IPN hydrogels with higher viscoelasticity. Inhibition studies emphasized the pivotal roles of actin dynamics and matrix metalloproteinase activity in iPSC cyst morphology, which varied with the viscoelastic properties of the hydrogels. Thus, the introduced sGAG-IPN hydrogel platform offers a powerful methodology for exogenous stem cell fate control.

Bio-orthogonal tuning of matrix properties during 3D cell culture to induce morphological and phenotypic changes.

Described herein is a protocol for producing a synthetic extracellular matrix that can be modified in situ during three-dimensional cell culture. The hydrogel platform is established using modular building blocks employing bio-orthogonal tetrazine (Tz) ligation with slow (norbornene, Nb) and fast (trans-cyclooctene, TCO) dienophiles. A cell-laden gel construct is created via the slow, off-stoichiometric Tz/Nb reaction. After a few days of culture, matrix properties can be altered by supplementing the cell culture media with TCO-tagged molecules through the rapid reaction with the remaining Tz groups in the network at the gel-liquid interface. As the Tz/TCO reaction is faster than molecular diffusion, matrix properties can be modified in a spatiotemporal fashion simply by altering the identity of the diffusive species and the diffusion time/path. Our strategy does not interfere with native biochemical processes nor does it require external triggers or a second, independent chemistry. The biomimetic three-dimensional cultures can be analyzed by standard molecular and cellular techniques and visualized by confocal microscopy. We have previously used this method to demonstrate how in situ modulation of matrix properties induces epithelial-to-mesenchymal transition, elicits fibroblast transition from mesenchymal stem cells and regulates myofibroblast differentiation. Following the detailed procedures, individuals with a bachelor's in science and engineering fields can successfully complete the protocol in 4-5 weeks. This protocol can be applied to model tissue morphogenesis and disease progression and it can also be used to establish engineered constructs with tissue-like anisotropy and tissue-specific functions.

Cell tumbling enhances stem cell differentiation in hydrogels via nuclear mechanotransduction.

Cells can deform their local niche in three dimensions via whole-cell movements such as spreading, migration or volume expansion. These behaviours, occurring over hours to days, influence long-term cell fates including differentiation. Here we report a whole-cell movement that occurs in sliding hydrogels at the minutes timescale, termed cell tumbling, characterized by three-dimensional cell dynamics and hydrogel deformation elicited by heightened seconds-to-minutes-scale cytoskeletal and nuclear activity. Studies inhibiting or promoting the cell tumbling of mesenchymal stem cells show that this behaviour enhances differentiation into chondrocytes. Further, it is associated with a decrease in global chromatin accessibility, which is required for enhanced differentiation. Cell tumbling also occurs during differentiation into other lineages and its differentiation-enhancing effects are validated in various hydrogel platforms. Our results establish that cell tumbling is an additional regulator of stem cell differentiation, mediated by rapid niche deformation and nuclear mechanotransduction.

Toward a Plasmon-Based Biosensor throughout a Thermoresponsive Hydrogel.

This study investigates the potential of thermoresponsive hydrogels as innovative substrates for future in vitro diagnostic (IVD) applications using AVAC technology, developed and patented by the Mecwins biomedical company. In order to convert the hydrogel in a substrate compatible with AVAC technology, the following prerequisites were established: (1) the hydrogel layer needs to be permeable to gold nanoparticles (AuNPs), and (2) the optical properties of the hydrogel should not interfere with the detection of AuNPs with AVAC technology. These two key aspects are evaluated in this work. A silicon substrate (Sil) was coated with a layer of a thermosensitive hydrogel (TSH) based on poly(N-isopropylacrylamide-co-N,N'-methylene bis(acrylamide) (PNIPAAm-co-MBA). The TSH offers the advantage of easy modulation of its porosity through cross-linker adjustments, crucial for the plasmonic nanoparticle (NP) permeation. The platforms, denominated as (Sil)-g-(PNIPAAm-co-MBA), were fabricated by changing the cross-linker concentrations and exploring three deposition methods: drop casting (DC), spin coating (SC), and 3D printing (3D); the DC approach resulted in a very homogeneous and thin hydrogel layer, very suitable for the final application. Furthermore, after physical-chemical characterization, the TSH demonstrated its functionality in regulating nanoparticle absorption, and AVAC technology's capability to precisely identify such NPs through the hydrogel matrix was validated. The proposed hydrogel platform fulfills the initial requirements, opening the possibility for employing these hydrogels as dynamic substrates in sandwich immunoassay devices. The next step in the development of the hydrogel substrate would be its functionalization with biorecognition groups to allow for biomarker detection. By leveraging their enhanced capture efficiency and the ability to manipulate particle flow thermally, we anticipate a significant advancement in diagnostic methodologies, combining the spatial benefits of three-dimensional hydrogel structures with the precision of AVAC's digital detection.

Gellan gum-based multifunctional hydrogel with enduring sterilization and ROS scavenging for infected wound healing

The progression of severe skin injury healing can be easily impeded by bacterial infections and the resultant overproduction of reactive oxygen species (ROS) within the wound microenvironment. In this study, we developed a multifunctional antibacterial hydrogel by integrating gallium ion-tannic acid and polydopamine particles into gellan gum via a facile heat-cooling process. By harnessing the synergistic effects of polydopamine for short-term photothermal therapy and gallium ion for long-term chemotherapy, the hydrogel obtained shows outstanding antibacterial activities. Sustained release of gallium ion and tannic acid ensures a prolonged sterilization along with ROS-scavenging benefits. Moreover, this hydrogel demonstrates superior cytocompatibility, hemostatic properties, as well as capabilities including promoting cell migration, and adsorption to bacterial cells and toxin. The therapeutic efficacy of the hydrogel was validated using a mouse model of MRSA-induced cutaneous infections. Overall, this work introduces a straightforward yet highly efficient multifunctional hydrogel platform that combines synergetic antibacterial actions, ROS scavenging, and hemostasis to enhance the healing of bacteria-associated wounds.

Cartilage regeneration achieved in photo-crosslinked hyaluronic hydrogel bioactivated by recombinant humanized collagen type III

Collagen has been extensively investigated as a bioactive material in cartilage tissue engineering. Recombinant humanized collagen type III (rhCol III) possessed excellent biocompatibility and imperative interactions with various cells shows a significant advantage as the starting material of medical devices. To investigate the bioactivation effect of rhCol III in cartilage tissue engineering, methacrylated hyaluronic acid (HA-MA) was prepared and rhCol III was further compounded to establish a photo-crosslinked composite hydrogel (HA-rhCol Ⅲ) platform to study the cartilage regeneration with chondrocytes encapsulated. The results verified that the HA-rhCol III hydrogels could be rapidly formed with stable mechanical properties using the blue light curing system. Meanwhile, the rhCol III could be effectively retained inside the composite hydrogel, which was conducive to maintain its bioactive function for a longer period. In vitro cell experiments confirmed that rhCol III improved the local microenvironment for chondrocytes, which provided abundant adhesion sites and further promoted cell migration, proliferation and differentiation. In vivo results indicated that the composite hydrogels could be conveniently applied to fulfill the cartilage defect in rabbit, and the histological and immunohistological results suggested that cartilage regeneration could be achieved with the application of HA-rhCol Ⅲ composite hydrogels. It could be concluded that the addition of rhCol III could bioactivate the hydrogel and promote the tissue regeneration, showing potential for application in tissue engineering.

Photoactivated Hydrogel Therapeutic System with MXene-Based Nanoarchitectonics Potentiates Endogenous Bone Repair Through Reshaping the Osteo-Vascularization Network.

The repair and reconstruction of large-scale bone defects face enormous challenges because of the failure to reconstruct the osteo-vascularization network. Herein, a near-infrared (NIR) light-responsive hydrogel system is reported to achieve programmed tissue repair and regeneration through the synergetic effects of on-demand drug delivery and mild heat stimulation. The spatiotemporal hydrogel system (HG/MPa) composed of polydopamine-coated Ti3C2Tx MXene (MP) nanosheets decorated with acidic fibroblast growth factor (aFGF, a potent angiogenic drug) and hydroxypropyl chitosan/gelatin (HG) hydrogel is developed to orchestrate the reconstruction of the osteo-vascularization network and boost bone regeneration. Upon exposure to NIR light irradiation, the engineered HG/MPa hydrogel can achieve the initial complete release of aFGF to induce rapid angiogenesis and provide sufficient blood supply, maximizing its biofunction in the defect area. This integrated hydrogel system demonstrated good therapeutic efficacy in promoting cell adhesion, proliferation, migration, angiogenesis, and osteogenic differentiation through periodic NIR irradiation. In vivo, animal experiments further revealed that the spatiotemporalized hydrogel platform synergized with mild photothermal treatment significantly accelerated critical-sized bone defect healing by increasing the osteo-vascularization network density, recruiting endogenous stem cells, and facilitating the production of osteogenesis/angiogenesis-related factors. Overall, smart-responsive hydrogel couldenhance the reconstruction of the osteo-vascularization network in bone regeneration.

Tuning a bioengineered hydrogel for studying astrocyte reactivity in glioblastoma

Astrocytes play many essential roles in the central nervous system (CNS) and are altered significantly in disease. These reactive astrocytes contribute to neuroinflammation and disease progression in many pathologies, including glioblastoma (GB), an aggressive form of brain cancer. Current in vitro platforms do not allow for accurate modeling of reactive astrocytes. In this study, we sought to engineer a simple bioengineered hydrogel platform that would support the growth of primary human astrocytes and allow for accurate analysis of various reactive states. After validating this platform using morphological analysis and qPCR, we then used the platform to begin investigating how astrocytes respond to GB derived extracellular vesicles (EVs) and soluble factors (SF). These studies reveal that EVs and SFs induce distinct astrocytic states. In future studies, this platform can be used to study how astrocytes transform the tumor microenvironment in GB and other diseases of the CNS. Statement of significanceRecent work has shown that astrocytes help maintain brain homeostasis and may contribute to disease progression in diseases such as glioblastoma (GB), a deadly primary brain cancer. In vitro models allow researchers to study basic mechanisms of astrocyte biology in healthy and diseased conditions, however current in vitro systems do not accurately mimic the native brain microenvironment. In this study, we show that our hydrogel system supports primary human astrocyte culture with an accurate phenotype and allows us to study how astrocytes change in response to a variety of inflammatory signals in GB. This platform could be used further investigate astrocyte behavior and possible therapeutics that target reactive astrocytes in GB and other brain diseases.

Hydrogels with Independently Controlled Adhesion Ligand Mobility and Viscoelasticity Increase Cell Adhesion and Spreading.

A primary objective in designing hydrogels for cell culture is recreating the cell-matrix interactions found within human tissues. Identifying the most important biomaterial features for these interactions is challenging because it is difficult to independently adjust variables such as matrix stiffness, stress relaxation, the mobility of adhesion ligands and the ability of these ligands to support cellular forces. In this work we designed a hydrogel platform consisting of interpenetrating polymer networks of covalently crosslinked poly(ethylene glycol) (PEG) and self-assembled peptide amphiphiles (PA). We can tailor the storage modulus of the hydrogel by altering the concentration and composition of each network, and we can tune the stress relaxation half-life through the non-covalent bonding in the PA network. Ligand mobility can be adjusted independently of the matrix mechanical properties by attaching the RGD cell adhesion ligand to either the covalent PEG network, the dynamic PA network, or both networks at once. Interestingly, our findings show that endothelial cell adhesion formation and spreading is maximized in soft, viscoelastic gels in which RGD adhesion ligands are present on both the covalent PEG and non-covalent PA networks. The dynamic nature of cell adhesion domains, coupled with their ability to exert substantial forces on the matrix, suggests that having different presentations of RGD ligands which are either mobile or are capable of withstanding significant forces are needed mimic different aspects of complex cell-matrix adhesions. By demonstrating how different presentations of RGD ligands affect cell behavior independently of viscoelastic properties, these results contribute to the rational design of hydrogels that facilitate desired cell-matrix interactions, with the potential of improving in vitro models and regenerative therapies.

Fabrication of multi-responsive dynamic poly(ethylene glycol)-iron oxide nanoparticle nanocomposite hydrogels through interfacial boronate-catechol crosslinking

Poly(ethylene glycol) (PEG)-based nanocomposite (NC) hydrogel with multiple advantageous properties such as high mechanical strength and stimuli-responsiveness have been demonstrated as promising materials across various fields. Here, an innovative type of PEG-based NC hydrogels is fabricated using phenylboronic acid-polyethyleneimine (PBA-PEI)-functionalized iron oxide nanoparticles (PP-IOPs) to crosslink the dopamine-modified 4arm-PEG (DA-4APEG) through boronate-catechol crosslinking. DA-4APEG/PP-IOP NC hydrogels exhibit tunable microstructures (i.e., pore size) and properties (i.e., rheological, mechanical, and swelling behaviors) by changing the number of PP-IOPs in the hydrogel network. With the dynamic crosslinks and magnetic nanoparticles in the network, DA-4APEG/PP-IOP NC hydrogels are self-healable and also responsive to various stimuli, including temperature, pH, glucose, dopamine, hydrogen peroxide, magnetic field, and near-infrared light. Therefore, a versatile PEG-based hydrogel platform has been developed, featuring customizable properties, multiple stimuli-responsiveness, and dynamic characteristics, making it suitable for advanced applications.

Ascorbyl palmitate nanofiber-reinforced hydrogels for drug delivery in soft tissues

Nanofiber-based hydrogel delivery systems have recently shown great potential in biomedical applications, specifically due to their high surface-to-volume ratio of ultra-fine nanofibers and their ability to carry low solubility drugs. Herein, we introduce a visible light-triggered in situ-gelling drug vehicle (GAP Gel) composed of ascorbyl palmitate (AP) nanofibers and gelatin methacryloyl polymer. AP nanofibers form self-assembled structures through intermolecular interactions with a hydrophobic drug-loading core. We demonstrate that the hydrophilic periphery of AP nanofibers allows them to interact with other hydrophilic molecules via hydrogen bonds. The presence of AP nanofibers significantly enhances the viscoelasticity of GAP Gel in a concentration-dependent manner. Further, GAP Gel shows in vitro biocompatibility and sustained drug delivery efficacy when loaded with a hydrophobic antibiotic. Likewise, GAP Gel shows excellent in vivo biocompatibility when implanted in immunocompetent mice in various forms. Lastly, GAP Gels maintain cell viability when cultured in a 3D-environment over 7 days, establishing it as a promising and versatile hydrogel platform for the delivery of biotherapeutics.

An Intelligent Hydrogel Platform with Triple‐Triggered On‐Demand Release for Accelerating Diabetic Wound Healing

An Intelligent Hydrogel Platform with Triple‐Triggered On‐Demand Release for Accelerating Diabetic Wound Healing