Hydrogel dressings have received extensive attention for the skin wound repair, while it is still a challenge to develop a smart hydrogel for adapting the dynamic wound healing process. Herein, we develop a novel graphene oxide (GO) hybrid hydrogel scaffold with adjustable mechanical properties, controllable drug release, and antibacterial behavior for promoting wound healing. The scaffold was prepared by injecting benzaldehyde and cyanoacetate group-functionalized dextran solution containing GO into a collection pool of histidine. As the GO possesses obvious photothermal behavior, the hybrid hydrogel scaffold exhibited an obvious stiffness decrease and effectively promoted cargo release owing to the breaking of the thermosensitive C=C double bond at a high temperature under NIR light. In addition, NIR-assisted photothermal antibacterial performance of the scaffold could be also achieved with the local temperature rising after irradiation. Therefore, it is demonstrated that the GO hybrid hydrogel scaffold with vascular endothelial growth factor (VEGF) encapsulation can achieve the adjustable mechanical properties, photothermal antibacterial, and angiogenesis during the wound healing process. These features indicated that the proposed GO hybrid hydrogel scaffold is potentially valuable for promoting wound healing and other biomedical application.

Electronic skins with distinctive features have attracted remarkable attention from researchers because of their promising applications in flexible electronics. Here, we present novel morphologically conductive hydrogel microfibers with MXene encapsulation by using a multi-injection coflow glass capillary microfluidic chip. The coaxial flows in microchannels together with fast gelation between alginate and calcium ions ensure the formation of hollow straight as well as helical microfibers and guarantee the in situ encapsulation of MXene. The resultant hollow straight and helical MXene hydrogel microfibers were with highly controllable morphologies and package features. Benefiting from the easy manipulation of the microfluidics, the structure compositions and the sizes of MXene hydrogel microfibers could be easily tailored by varying different flow rates. It was demonstrated that these morphologically conductive MXene hydrogel microfibers were with outstanding capabilities of sensitive responses to motion and photothermal stimulations, according to their corresponding resistance changes. Thus, we believe that our morphologically conductive MXene hydrogel microfibers with these excellent features will find important applications in smart flexible electronics especially electronic skins.

As a novel cellular therapy, the anti-inflammatory and immunomodulatory virtues of mesenchymal stem cells (MSCs) make them promising candidates for systemic sclerosis (SSc) treatment. However, the clinical efficacy of this stratagem is limited because of the short persistence time, poor survival, and engraftment of MSCs after injection in vivo. Herein, we develop a novel MSCs-laden injectable self-healing hydrogel for SSc treatment. The hydrogel is prepared using N, O-carboxymethyl chitosan (CS-CM) and 4-armed benzaldehyde-terminated polyethylene glycol (PEG-BA) as the main components, imparting with self-healing capacity via the reversible Schiff-base connection between the amino and benzaldehyde groups. We demonstrate that the hydrogel laden with MSCs not only promoted the proliferation of MSCs and increased the cellular half-life in vivo, but also improve their immune-modulating functions. The tube formation assay indicates that the MSCs could significantly promote angiopoiesis. Moreover, the MSCs-laden hydrogel could inhibit fibrosis by modulating the synthesis of collagen and ameliorate disease progression in SSc disease model mice after subcutaneous injection of bleomycin. All these results highlight this novel MSCs-laden hydrogel and its distinctive functions in treatment of chronic SSc, indicating the additional potential to be used widely in the clinic.

Wound healing has become a worldwide healthcare issue. Attempts in the area focus on developing patches with the capabilities of avoiding wound infection, promoting tissue remolding, and reporting treatment status that are of great value for wound treatment.

Electronic skins have received increasing attention in biomedical areas. Current efforts about electronic skins are focused on the development of multifunctional materials to improve their performance. Here, the authors propose a novel natural-synthetic polymers composite structural color hydrogel film with high stretchability, flexibility, conductivity, and superior self-reporting ability to construct ideal multiple-signal bionic electronic skins. The composite hydrogel film is prepared by using the mixture of polyacrylamide (PAM), silk fibroin (SF), poly(3,4-ethylenedioxythiophene):poly (4-styrene sulfonate) (PEDOT:PSS, PP), and graphene oxide (GO) to replicate colloidal crystal templates and construct inverse opal scaffolds, followed by subsequent acid treatment. Due to these specific structures and components, the resultant film is imparted with vivid structural color and high conductivity while retaining the composite hydrogel's original stretchability and flexibility. The authors demonstrate that the composite hydrogel film has obvious color variation and electromechanical properties during the stretching and bending process, which could thus be utilized as a multi-signal response electronic skin to realize real-time color sensing and electrical response during human motions. These features indicate that the proposed composite structural color hydrogel film can widen the practical value of bionic electronic skins.

Hard-healing diabetic wound brings burgeoning physical and mental burdens to patients. Current treatment strategies tend to achieve multistage promotion and real-time reporting to facilitate wound management. Herein, a biomimetic enzyme cascade inverse opal microparticles system for wound healing, which is intergated with glucose oxidase (GOD) and copper peroxide (CP). Such microparticles are composed of biofriendly hyaluronic acid methacryloyl (HAMA) and pH-responsive acrylic acid (AA), which provided abundant binding sites and spaces for chemical immobilizing and physical doping of enzymes and metal bioinorganics. When the cascade catalytic system is applied on wound sites, hyperglycemia environment would serve as a hydrogen peroxide (H2 O2 ) generator through GOD catalysis, while acidic environment triggers the decomposition of CP, further catalyzing H2 O2 to generate reactive oxygen species (ROS). Additionally, the distinctive structural color of the microparticles can visually reflect the wound pH and intelligently estimate the healing state. It is demonstrated that such microparticle systems exhibit excellent broad-spectrum antibacterial and angiogenesis-promoting properties, as well as significant real-time reporting ability for wound healing. These features indicate that enzyme cascade structural color microparticles possess valuable potential in wound healing and related field.

The treatment of diabetic wounds remains a great challenge for medical community. Here, we present a novel structural color supramolecular hydrogel patch for diabetic wound treatment. This hydrogel patch was created by using N-acryloyl glycinamide (NAGA) and 1-vinyl-1,2,4-triazole (VTZ) mixed supramolecular hydrogel as the inverse opal scaffold, and temperature responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel loaded with vascular endothelial cell growth factor (VEGF) as a filler. Supramolecular hydrogel renders hydrogel patch with superior mechanical properties, in which NAGA and VTZ also provide self-healing and antibacterial properties, respectively. Besides, as the existence of PNIPAM, the hydrogel patch was endowed with thermal-responsiveness property, which could release actives in response to temperature stimulus. Given these excellent performances, we have demonstrated that the supramolecular hydrogel patch could significantly enhance the wound healing process in diabetes rats by downregulating the expression of inflammatory factors, promoting collagen deposition and angiogenesis. Attractively, due to responsive optical property of inverse opal scaffold, the hydrogel patch could display color-sensing behavior that was suitable for the wound monitoring and management as well as guidance of clinical treatment. These distinctive features indicate that the presented hydrogel patches have huge potential values in biomedical fields.

Chemotherapy is an essential postoperative treatment for pancreatic cancer, while due to the lack of effective drug evaluation platforms, the therapeutic outcomes are hampered by tumor heterogeneity among individuals. Here, a novel microfluidic encapsulated and integrated primary pancreatic cancer cells platform is proposed for biomimetic tumor 3D cultivation and clinical drug evaluation. These primary cells are encapsulated into hydrogel microcapsules of carboxymethyl cellulose cores and alginate shells based on a microfluidic electrospray technique. Benefiting from the good monodispersity, stability, and precise dimensional controllability of the technology, the encapsulated cells can proliferate rapidly and spontaneously form 3D tumor spheroids with highly uniform size and good cell viability. By integrating these encapsulated tumor spheroids into a microfluidic chip with concentration gradient channels and culture chambers, dynamic and high-throughput drug evaluation of different chemotherapy regimens could be realized. It is demonstrated that different patient-derived tumor spheroids show different drug sensitivity on-chip, which is significantly consistent with the clinical follow-up study after the operation. The results demonstrate that the microfluidic encapsulated and integrated tumor spheroids platform has great application potential in clinical drug evaluation.

Wound healing is a complex physiological process that involves coordinated phases such as inflammation and neovascularization. Attempts to promote the healing process tend to construct an effective delivery system based on different drugs and materials. In this paper, we propose novel MXene-integrated microneedle patches with adenosine encapsulation for wound healing. Owing to the dynamic covalent bonding capacity of boronate molecules with adenosine, 3-(acrylamido)phenylboronic acid- (PBA-) integrated polyethylene glycol diacrylate (PEGDA) hydrogel is utilized as the host material of microneedle patches. Benefitting from photothermal conversion capacity of MXene, the release of loaded adenosine could be accelerated under NIR irradiation for maintaining the activation signal around injury site. In vitro cell experiments proved the effect of MXene-integrated microneedle patches with adenosine encapsulation in enhancing angiogenesis. When applied for treating animal models, it is demonstrated that the microneedle patches efficiently promote angiogenesis, which is conductive to wound healing. These features make the proposed microneedle patch potential for finding applications in wound healing and other biomedical fields.

Management of infected wounds has raised worldwide concerns. Attempts in this field focus on the development of intelligent patches for improving the wound healing. Here, inspired by the cocktail treatment and combinational therapy stratagem, we present a novel Janus piezoelectric hydrogel patch via 3-dimensional printing for sonodynamic bacteria elimination and wound healing. The top layer of the printed patch was poly(ethylene glycol) diacrylate hydrogel with gold-nanoparticle-decorated tetragonal barium titanate encapsulation, which realizes the ultrasound-triggered release of reactive oxygen species without leaking nanomaterials. The bottom layer is fabricated with methacrylate gelatin and carries growth factors for the cell proliferation and tissue reconstruction. Based on these features, we have demonstrated in vivo that the Janus piezoelectric hydrogel patch can exert substantial infection elimination activity under the excitation of ultrasound, and its sustained release of growth factors can promote tissue regeneration during wound management. These results indicated that the proposed Janus piezoelectric hydrogel patch had practical significance in sonodynamic infection alleviation and programmable wound healing for treating different clinical diseases.

In the drug therapy of tumor, efficient and stable drug screening platforms are required since the drug efficacy varies individually. Here, inspired by the microstructures of hepatic lobules, in which hepatocytes obtain nutrients from both capillary vessel and the central vein, we present a novel hierarchical hydrogel system with ordered micro-nano structure for liver cancer-on-a-chip construction and drug screening. The hierarchical hydrogel system was fabricated by using pregel to fill and replicate self-assembled colloidal crystal arrays and microcolumn array template. Due to the synergistic effect of its interconnected micro-nano structures, the resultant system could not only precisely control the size of cell spheroids but also realize adequate nutrient supply of cell spheroids. We have demonstrated that by integrating the hierarchical hydrogel system into a multichannel concentration gradients microfluidic chip, a functional liver cancer-on-a-chip could be constructed for high-throughput drug screening with good repeatability and high accuracy. These results indicated that the hierarchical hydrogel system and its derived liver cancer-on-a-chip are ideal platforms for drug screening and have great application potential in the field of personalized medicine.

Heart-on-a-chip plays an important role in revealing the biological mechanism and developing new drugs for cardiomyopathy. Tremendous efforts have been devoted to developing heart-on-a-chip systems featuring simplified fabrication, accurate imitation and microphysiological visuality. In this paper, the authors present a novel electroconductive and anisotropic structural color hydrogel by simply polymerizing non-close-packed colloidal arrays on super aligned carbon nanotube sheets (SACNTs) for visualized and accurate heart-on-a-chip construction. The generated anisotropic hydrogel consists of a colloidal array-locked hydrogel layer with brilliant structural color on one surface and a conductive methacrylated gelatin (GelMA)/SACNTs film on the other surface. It is demonstrated that the anisotropic morphology of the SACNTs could effectively induce the alignment of cardiomyocytes, and the conductivity of SACNTs could contribute to the synchronous beating of cardiomyocytes. Such consistent beating rhythm caused the deformation of the hydrogel substrates and dynamic shifts in structural color and reflection spectra of the whole hybrid hydrogels. More attractively, with the integration of such cardiomyocyte-driven living structural color hydrogels and microfluidics, a visualized heart-on-a-chip system with more consistent beating frequency has been established for dynamic cardiomyocyte sensing and drug screening. The results indicate that the electroconductive and anisotropic structural color hydrogels are potential for various biomedical applications.

Wound healing and tissue repair are recognized as basic human health problems worldwide. Attempts to accelerate the reparative process are focused on developing functional wound dressings. Herein, we present novel Janus textiles with anisotropic wettability from hierarchical microfluidic spinning for wound healing. The hydrophilic hydrogel microfibers from microfluidics are woven into textiles for freeze-drying treatment, followed by the deposition of electrostatic spinning nanofibers composed of hydrophobic polylactic acid (PLA) and silver nanoparticles. The electrospun nanofiber layer can be well coupled with the hydrogel microfiber layer to generate Janus textiles with anisotropic wettability due to the roughness of the hydrogel textile surface and the incomplete evaporation of PLA solution when reaching the surface. For wound treatment with the hydrophobic PLA side contacting the wound surface, the wound exudate can be pumped from the hydrophobic to the hydrophilic side based on the wettability differential derived drainage force. During this process, the hydrophobic side of the Janus textile can prevent excess fluid from infiltrating the wound again, preventing excessive moisture and preserving the breathability of the wound. In addition, the silver nanoparticles contained in the hydrophobic nanofibers could impart the textiles with good antibacterial effect, which further promote the wound healing efficiency. These features indicate that the described Janus fiber textile has great application potential in the field of wound treatment.

Microparticles with strong adherence are expected as efficient drug delivery vehicles. Herein, we presented an ingenious hydrogel microparticle recapitulating the adhesion mechanism of Boston ivy tendrils adhesive discs (AD) for durable drug delivery. The particles were achieved by replicating a silica colloidal crystal aggregates assembled in a droplet template after rapid solvent extraction. Due to their unique shape, the nanostructure, and the sticky hydrogel component, such novel microparticles exhibited prominent adhesive property to the wet tissue environment. It was demonstrated that the bioinspired microcarriers loading with dexamethasone had a good therapeutic effect for ulcerative colitis due to the strong adhesion ability for prolonging the maintenance of drug availability. These virtues make the biomimetic microparticles potentially ideal for many practical clinical applications, such as drug delivery, bioimaging, and biodiagnostics.

Structural color materials have been studied for decades because of their fascinating properties. Effects in this area are the trend to develop functional structural color materials with new components, structures, or morphologies for different applications. In this study, we found that the coassembled graphene oxide (GO) and colloid nanoparticles in droplets could form component phase separations, and thus, previously unknown anisotropic structural color particles (SCPs) with hemispherical colloidal crystal cluster and oblate GO component could be achieved. The anisotropic SCPs, as well as their inverse opal hydrogel derivatives, were endowed with brilliant structural colors and controllable capabilities of fixation, location, orientation, and even responsiveness due to their specific structure, morphology, and components. We have also demonstrated that the anisotropic hydrogel SCPs with these features were ideal candidates for dynamic cell monitoring and sensing. These properties indicate that the anisotropic SCPs and their derivatives have huge potential values in biomedical areas.

Mimicking subcellular compartments containing enzymes in organisms is considered a promising approach to substitute for missing or lost cellular functions. Inspired by the multicompartment structures of cellular architectures, we present a novel multienzyme system based on hollow hydrogel microcapsules with flexible enzymatic inverse opal particles. Benefiting from the precise operation capability of the microfluidic electrospray and the remarkable structural color marks in the inverse opal particles, we developed a multienzyme system with controllable number, type, and spatial arrangement of the encapsulated enzymes. The hydrogel shells also could improve enzyme stability against proteolysis in the system. The multienzyme system containing alcohol oxidase and catalase could act as a cascade biocatalyst and reduce alcohol levels in media, providing an alternative antidote and prophylactic for alcohol intoxication. These features indicated that our strategy provides an ideal enzyme cascade reaction system for complex biocatalysis and biomimetic functions of some organelles or organs.

Patch plays an important role in clinical medicine for its broad applications in tissue repair and regeneration. Here, inspired by the diverse adhesion, anti-adhesion, and responsive structural color phenomena in biological interfaces, we present a hybrid hydrogel film with an adhesive polydopamine (PDA) layer and an anti-adhesive poly(ethylene glycol) diacrylate (PEGDA) layer in an inverse opal scaffold. It was demonstrated that the resultant hydrogel film could serve as a functional tissue patch with an excellent adhesion property on one surface for repairing injured tissues and an anti-adhesion property on the other surface for preventing adverse adhesion. Besides, because of the responsive structural color, the patch was imparted with self-reporting mechanical capability, which could provide a real-time color-sensing feedback to monitor the heartbeat activity. Moreover, the catechol groups on PDA imparted the patch with high tissue adhesiveness and self-healing capability in vivo. These features give the bioinspired patch high potential in biomedical applications.

Chronic hard-to-heal wounds draw great attention worldwide, as their treatments are limited by infections and hypoxia. Inspired by the natural oxygen production capacity of algae and the competitive advantage of beneficial bacteria over other microbes, we presented a living microecological hydrogel (LMH) with functionalized Chlorella and Bacillus subtilis encapsulation to realize continuous oxygen delivery and anti-infections for promoting chronic wound healing. As the hydrogel consisted of thermosensitive Pluronic F-127 and wet-adhesive polydopamine, the LMH could keep liquid at a low temperature while quickly solidifying and tightly adhering to the wound bed. It was demonstrated that by optimizing the proportion of the encapsulated microorganism, the Chlorella could continuously produce oxygen to relieve hypoxia and support the proliferation of B. subtilis, while B. subtilis could eliminate the colonized pathogenic bacteria. Thus, the LMH substantially promoted the healing of infected diabetic wounds. These features make the LMH valuable for practical clinical applications.

Stem cell therapies have made great progress in the treatment of diabetic wounds during recent decades, while their short in vivo residence, alloimmune reactions, undesired behaviors, and dramatic losses of cell functions still hinder the translation of them into clinic. Here, inspired by the natural components of stem cell niches, we presented novel microfluidic hydrogel microcarriers with extracellular matrix (ECM)-like composition and adipose-derived stem cells (ADSCs) encapsulation for diabetic wound healing. As the hydrogel was synthesized by conjugating hyaluronic acid methacryloyl (HAMA) onto the Fibronectin (FN) molecule chain (FN-HAMA), the laden ADSCs in the microcarriers showed improved bioactivities and pro-regenerative capabilities. Based on these features, we have demonstrated that these ADSCs microcarriers exhibited significant promotion of neovascularization, follicular rejuvenation, and collagen deposition in a mouse diabetic wound model. These results indicated that the stem cell niche-inspired FN-HAMA microcarriers with ADSCs encapsulation have great clinical potential for diabetic wound treatment.

Medical patches play an important role in wound healing because of their tissue conformality, drug release capacity, and convenient operation. Great efforts have been devoted to developing new-generation patches with distinctive features promoting wound healing. Here, inspired by the structure of octopus suction cups and the component of natural tissue, a biocompatible wound patch with selective adhesiveness and individualized design using a combined strategy of template-replication and mask-guided lithography is presented. Such patches are based on Ecoflex film with suction-cup-mimicking microstructures to adhere to normal skin and with biocompatible gelatin methacryloyl (GelMA) hydrogel to contact wounded areas. An ultraviolet mask with a tailorable pattern is employed to shape the GelMA hydrogel into customized geometry replicating individual wound areas, and thus both adhesion and antiadhesion properties are integrated into the same patch. In addition, vascular endothelial growth factor is loaded to accelerate the healing process. Based on these advantages, the authors demonstrate that the present patches not only adhere to different skin surfaces, but also promote the treatment of a rat cutaneous wound model. Thus, it is believed that this versatile patch can break through the limitation of traditional patches and be ideal candidates for wound healing and related biomedical applications.