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.

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.

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.

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.

Micromotors have opened novel avenues for drug delivery due to their capacity for self-propelling. Attempts in this field trend towards ameliorating their functions to promote their clinical applications. In this paper, an ingenious suction-cup-inspired micromotor is presented with adhesive properties for drug delivery in the stomach. The micromotors are fabricated by using hydrogel replicating the structure of suction-cup-like microparticles, which derive from self-assembly of colloidal crystals under rapid solvent extraction, followed by loading magnesium (Mg) in the bottom spherical surface. The Mg-loaded micromotors can realize spontaneous movement due to the continual generation of hydrogen bubbles in gastric juice. The combination of unique suction-cup-like structure with excellent motion performance makes the micromotor an ideal carrier for drug delivery as they can efficiently adhere to the tissue. Moreover, benefiting from the porous structure, the hydrogel micromotors exhibit a high volume-surface ratio, which enables efficient drug loading. It is demonstrated that the suction-cup-inspired micromotors can adhere efficiently to the ulcer-region in the stomach and release drugs due to their distinctive architecture and spontaneous motion, exhibiting desirable curative effect of gastric ulcer. Thus, the suction-cup-inspired micromotors with adhesive properties are expected to advance the development of micromotor in clinical applications.

Developing a self-reporting bioadhesive patch that has strong adhesion to the wet tissues and meanwhile can avoid adhering to the adjacent tissues is a current research difficulty and challenge. In this paper, inspired by the wet adhesion of spider web, slippery surface of Nepenthes, and structural color phenomena of chameleons, a novel structural color medical patch with surface dual-properties of wet bioadhesion and slipperiness for internal tissue repair based on inverse opal scaffold is presented. The adhesive surface made by poly(acrylic acid)-polyethylene glycol-N-hydroxysuccinimide ester and gelatin hydrogel can attain tough adhesion to internal wet tissues by absorbing tissue interfacial water and the covalent cross-linking between the hydrogel and tissue. Besides, the slippery surface made by liquid paraffin infused inverse opal scaffold can avoid adhesion to the adjacent tissues. It is demonstrated that the designed patch can adhere tightly to the defect tissue and improve the tissue repair without adjacent adhesion when applied in a rat model with full-thickness perforation of the stomach wall. In addition, the responsive structural color can supply a color-sensing monitoring to evaluate the adhesive and repair process. These features impart the bioinspired patch with great scientific significance and broad clinical application prospects.

Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSCIL-27 EVs) is developed to treat IBD. The MSCIL-27 EVs prepared through lentivirus-mediated gene transfection technology show ideal anti-inflammatory and damage repair function. By encapsulating MSCIL-27 EVs into dopamine methacrylamide-modified hydrogel, a bioadhesive EVs microcarrier via microfluidic technology is fabricated. The resultant microcarriers exhibit ideal MSCIL-27 EVs sustained release effect and effective wet adhesion property. Furthermore, the therapeutic potential of MSCIL-27 EVs-loaded microcarriers in treating IBD is demonstrated. Through giving IBD rats a rectal administration, it is found that the microcarriers can firmly anchor to the surface of colon, reduce the inflammatory response, and repair the damaged barrier. Therefore, the bioadhesive MSCIL-27 EVs-loaded microcarriers provide a promising strategy for the biomedical application of MSC-derived EVs, and broaden the clinical potential of MSC therapy.

Biological scaffolds hold promising perspectives for random skin flap regeneration, while the practical application is greatly limited by their insufficient vascularization ability and the lack of responsiveness during the dynamical healing process. Herein, a novel MXene-incorporated hollow fibrous (MX-HF) scaffold with dynamically responsive channels is presented for promoting vascularization and skin flap regeneration by using a microfluidic-assisted 3D printing strategy. Benefiting from the photothermal conversion capacity of the MXene nanosheets and temperature-responsive ability of poly(NIPAM) hydrogels in the MX-HF scaffolds, they display a near-infrared (NIR)-responsive shrinkage/swelling behavior, which facilitates the cell penetration into the scaffold channels from the surrounding environment. Moreover, by incorporating vascular endothelial growth factor (VEGF) into the hydrogel matrix for controllable delivery, the MX-HF scaffolds can achieve promoted proliferation, migration, and proangiogenic effects of endothelial cells under NIR irradiation. It is further demonstrated in vivo that the NIR-responsive VEGF@MX-HF scaffolds can effectively improve skin flap survival by promoting angiogenesis, decreasing inflammation, and attenuating apoptosis in skin flaps. Thus, it is believed that such responsive MX-HF scaffolds are promising candidates for clinical random skin flap regeneration as well as other diverse tissue engineering applications.