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.

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.

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.

Microneedles have attracted increasing interest among various medical fields due to their painless, noninvasive, and efficient way of drug delivery. However, practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity. Here, inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles, we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities. With polydopamine hydrogel as the microneedle base and a loop of suction-cup-structured concave chambers encircling each microneedle, the generated microneedles can fit the skin well; keep strong adhesion in dry, moist, and wet environments; and realize self-repair after being split into two parts. Besides, as polymyxin is loaded into both the hydrogel tips and the polydopamine base, the microneedles are endowed with excellent ability to resist common bacteria during storage and usage. We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model. These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems.

Traditional Chinese medicine, such as Tripterygium wilfordii and Paeonia lactiflora, has potential values in treating systemic sclerosis (SSc) and other autoimmune diseases, while their toxic side effect elimination and precise tropical drug delivery are still challenges. Here, we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus (BP) microneedles (MNs) with the desired features for the SSc treatment. By employing a template-assisted layer-by-layer curing method, such MNs with triptolide (TP)/paeoniflorin (Pae) needle tips and BP-hydrogel needle bottoms could be well generated. The combined administration of TP and Pae can not only provide anti-inflammatory, detoxification, and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery. Besides, the additive BPs possess good biocompatibility and near-infrared (NIR) responsiveness, imparting the MN photothermal-controlled drug release capability. Based on these features, we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia, reduce collagen deposition, and reduce epidermal thickness in the SSc mouse models. These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

Three-dimensional (3D) porous scaffolds have a demonstrated value for tissue engineering and regenerative medicine. Inspired by the predation processes of marine predators in nature, we present new photocontrolled shrinkable inverse opal graphene oxide (GO) hydrogel scaffolds for cell enrichment and 3D culture. The scaffolds with adjustable pore sizes and morphologies were created using a GO and N-isopropylacrylamide dispersed solution as a continuous phase of microfluidic emulsions for polymerizing and replicating. Because of the interconnected porous structures and the remotely controllable volume responsiveness of the scaffolds, the suspended cells could be enriched into the inner spaces of the scaffolds through predator-like swallowing and discharging processes. Hepatocyte cells concentrated in the scaffold pores could form denser 3D spheroids more quickly via the controlled compression force caused by the shrinking of the dynamic scaffolds. More importantly, with a program of scaffold enrichment with different cells, an unprecedented 3D multilayer coculture system of endothelial-cell-encapsulated hepatocytes and fibroblasts could be generated for applications such as liver-on-a-chip and bioartificial liver. It was demonstrated that the resultant multicellular system offered significant improvements in hepatic functions, such as albumin secretion, urea synthesis, and cytochrome P450 expression. These features of our scaffolds make them highly promising for the biomimetic construction of various physiological and pathophysiological 3D tissue models, which could be used for understanding tissue level biology and in vitro drug testing applications.