Recent advancements in flexible electronics have highlighted their potential in biomedical applications, primarily due to their human-friendly nature. This study introduces a new flexible electronic system designed for motion sensing in a biomimetic three-dimensional (3D) environment. The system features a self-healing gel matrix (chitosan-based hydrogel) that effectively mimics the dynamics of the extracellular matrix (ECM), and is integrated with a highly sensitive thin-film resistive strain sensor, which is fabricated by incorporating a cross-linked gold nanoparticle (GNP) thin film as the active conductive layer onto a biocompatible microphase-separated polyurethane (PU) substrate through a clean, rapid, and high-precision contact printing method. The GNP-PU strain sensor demonstrates high sensitivity (a gauge factor of ∼50), good stability, and waterproofing properties. The feasibility of detecting small motion was evaluated by sensing the beating of human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte spheroids embedded in the gel matrix. The integration of these components exemplifies a proof-of-concept for using flexible electronics comprising self-healing hydrogel and thin-film nanogold in cardiac sensing and offers promising insights into the development of next-generation biomimetic flexible electronic devices.

The rise of drug-resistant microorganisms has prompted the development of innovative strategies with the aim of addressing this challenge. Among the alternative approaches gaining increased attention are antimicrobial peptides (AMPs), a group of peptides with the ability to combat microbial pathogens. Here, we investigated a small peptide, KLVFF, derived from the Alzheimer\'s amyloid-β (Aβ) protein. While Aβ has been associated with the development of neurodegenerative diseases, the core part of the Aβ protein, namely the Aβ 16-20 fragment, has also been exploited to obtain highly functional biomaterials. In this study we found that KLVFF is capable of self-assembling into a fibrillar network to form a self-healing hydrogel. Moreover, this small peptide can undergo a transition from a gel to a liquid state following application of shear stress, in a reversible manner. As an AMP, this material exhibited both antibacterial and antifungal properties while remaining highly biocompatible and noncytotoxic toward mammalian cells. The propensity of the KLVFF hydrogel to rapidly assemble into highly ordered macroscopic structures makes it an ideal candidate for biomedical applications necessitating antimicrobial activity, such as wound healing.

Self-healing hydrogels have good mechanical strength, can endure greater external force, and have the ability to heal independently, resulting in a strong bond between the wound and the material. Bacterial biofilm infections are life-threatening. Clindamycin (Cly) can be produced in the form of a self-healing hydrogel preparation. It is noteworthy that the antibacterial self-healing hydrogels show great promise as a wound dressing for bacterial biofilm infection. In this study, we developed a polyvinyl alcohol/borax (PVA/B) self-healing hydrogel wound dressing that releases Cly. Four ratios of PVA, B, and Cly were used to make self-healing hydrogels: F1 (4%:0.8%:1%), F2 (4%:1.2%:1%), F3 (1.6%:1%), and F4 (4%:1.6%:0). The results showed that F4 had the best physicochemical properties, including a self-healing duration of 11.81 ± 0.34 min, swelling ratio of 85.99 ± 0.12%, pH value of 7.63 ± 0.32, and drug loading of 98.34 ± 11.47%. The B-O-C cross-linking between PVA and borax caused self-healing, according to FTIR spectra. The F4 formula had a more equal pore structure in the SEM image. The PVA/B-Cly self-healing hydrogel remained stable at 6 ± 2 °C for 28 days throughout the stability test. The Korsmeyer-Peppas model released Cly by Fickian diffusion. In biofilm-infected mouse wounds, PVA/B-Cly enhanced wound healing and re-epithelialization. Our results indicate that the PVA/B-Cly produced in this work has reliable physicochemical properties for biofilm-infected wound therapy.

Pursuing high-performance conductive hydrogels is still hot topic in development of advanced flexible wearable devices. Herein, a tough, self-healing, adhesive double network (DN) conductive hydrogel (named as OSA-(Gelatin/PAM)-Ca, O-(G/P)-Ca) was prepared by bridging gelatin and polyacrylamide network with functionalized polysaccharide (oxidized sodium alginate, OSA) through Schiff base reaction. Thanks to the presence of multiple interactions (Schiff base bond, hydrogen bond, and metal coordination) within the network, the prepared hydrogel showed outstanding mechanical properties (tensile strain of 2800 % and stress of 630 kPa), high conductivity (0.72 S/m), repeatable adhesion performance and excellent self-healing ability (83.6 %/79.0 % of the original tensile strain/stress after self-healing). Moreover, the hydrogel-based sensor exhibited high strain sensitivity (GF = 3.66) and fast response time (<0.5 s), which can be used to monitor a wide range of human physiological signals. Based on this, excellent compression sensitivity (GF = 0.41 kPa-1 in the range of 90-120 kPa), a three-dimensional (3D) array of flexible sensor was designed to monitor the intensity of pressure and spatial force distribution. In addition, a gel-based wearable sensor was accurately classified and recognized ten types of gestures, achieving an accuracy rate of >96.33 % both before and after self-healing under three machine learning models (the decision tree, SVM, and KNN). This paper provides a simple method to prepare tough and self-healing conductive hydrogel as flexible multifunctional sensor devices for versatile applications in fields such as healthcare monitoring, human-computer interaction, and artificial intelligence.

In this paper, a hydrogel material with efficient antibacterial, hemostatic, self-healing, and injectable properties was designed for the treatment of diabetic wounds. Firstly, quaternary ammonium salts were grafted with oxidized sodium alginate, and quaternized oxidized sodium alginate (QOSA) was synthesized. Due to the introduction of quaternary ammonium group it has antibacterial and hemostatic effects, at the same time, due to the presence of aldehyde group it can be reacted with carboxymethyl chitosan (CMCS) to form a hydrogel through the Schiff base reaction. Furthermore, deer antler blood polypeptide (DABP) was loaded into the hydrogel (QOSA&CMCS&DABP), showing good swelling ratio and bacteriostatic effect. In vitro and in vivo experiments demonstrated that the hydrogel not only quickly inhibited hepatic hemorrhage in mice and reduced coagulation index and clotting time in vitro, but also significantly enhanced collagen deposition at the wound site, accelerating wound healing. This demonstrates that the multifunctional hydrogel materials (QOSA&CMCS&DABP) have promising applications in the acceleration of skin wound healing and antibacterial promotion.

The dynamic interplay between cells and their native extracellular matrix (ECM) influences cellular behavior, imposing a challenge in biomaterial design. Dynamic covalent hydrogels are viscoelastic and show self-healing ability, making them a potential scaffold for recapitulating native ECM properties. We aimed to implement kinetically and thermodynamically distinct crosslinkers to prepare self-healing dynamic hydrogels to explore the arising properties and their effects on cellular behavior. To do so, aldehyde-substituted hyaluronic acid (HA) was synthesized to generate imine, hydrazone, and oxime crosslinked dynamic covalent hydrogels. Differences in equilibrium constants of these bonds yielded distinct properties including stiffness, stress relaxation, and self-healing ability. The effects of degree of substitution (DS), polymer concentration, crosslinker to aldehyde ratio, and crosslinker functionality on hydrogel properties were evaluated. The self-healing ability of hydrogels was investigated on samples of the same and different crosslinkers and DS to obtain hydrogels with gradient properties. Subsequently, human dermal fibroblasts were cultured in 2D and 3D to assess the cellular response considering the dynamic properties of the hydrogels. Moreover, assessing cell spreading and morphology on hydrogels having similar modulus but different stress relaxation rates showed the effects of matrix viscoelasticity with higher cell spreading in slower relaxing hydrogels.

Biodegradable self-healing hydrogels with antibacterial property attracted growing attentions in biomedication as wound dressings since they can prevent bacterial infection and promote wound healing process. In this research, a biodegradable self-healing hydrogel with ROS scavenging performance and enhanced tissue adhesion was fabricated from dopamine grafted oxidized pectin (OPD) and naphthoate hydrazide terminated PEO (PEO NH). At the same time, Fe3+ ions were incorporated to endow the hydrogel with near-infrared (NIR) triggered photothermal property to obtain antibacterial activity. The composite hydrogel showed good hemostasis performance based on mussel inspired tissue adhesion with biocompatibility well preserved. As expected, the composition of FeCl3 improved conductivity and endowed photothermal property to the hydrogel. The in vivo wound repairing experiment revealed the 808 nm NIR light triggered photothermal behavior of the hydrogel reduced the inflammation response and promoted wound repairing rate. As a result, this composite FeCl3/hydrogel shows great potential to be an excellent wound dressing for the treatment of infection prong wounds with NIR triggers.

The impairment of phenotype switching of pro-inflammatory M1 to pro-healing M2 macrophage induced by hyperglycemic microenvironment often elevates oxidative stress, impairs angiogenesis, and leads to chronic non-healing wounds in diabetic patients. Administration of M2 macrophage-derived exosomes (M2Exo) at wound site is known to polarize M1 to M2 macrophage and can accelerate wound healing by enhancing collagen deposition, angiogenesis, and re-epithelialization. In the present study, M2Exo were conjugated with oxidized hyaluronic acid and mixed with PEGylated silk fibroin to develop self-healing Exo-gel to achieve an efficient therapy for diabetic wounds. Exo-gel depicted porous networked morphology with self-healing and excellent water retention behaviour. Fibroblast cells treated with Exo-gel showed significant uptake of M2Exo that increased their proliferation and migration in vitro. Interestingly, in a diabetic wound model of wistar rats, Exo-gel treatment induced 75 % wound closure within 7 days with complete epithelial layer regeneration by modulating cytokine levels, stimulating fibroblast-keratinocyte interaction and migration, angiogenesis, and organized collagen deposition. Taken together, this study suggests that Exo-gel depict properties of an excellent wound healing matrix and can be used as a therapeutic alternative to treat chronic non-healing diabetic wounds.

Flap grafting is a common technique used to repair skin defects in orthopedics and plastic and reconstructive surgeries. However, oxidative stress injury caused by ischemia and ischemia-reperfusion injury at the distal end of the skin flap can cause flap necrosis. Curcumin is a natural compound with anti-inflammatory and antioxidant properties that tackle oxidative stress. However, its applicability is limited by its poor water solubility. Exosomes are membranous vesicles that can be loaded with hydrophobic drugs. They are widely studied in drug delivery applications and can be investigated to augment curcumin efficiency. In this study, a self-healing oxidized pullulan polysaccharide-carboxymethylated chitosan composite hydrogel was used as a curcumin-loaded exosome delivery system to evaluate its impact on the viability of skin flaps. The hydrogel exhibited good self-healing properties that allowed the continuous and stable release of drugs. It had anti-inflammatory and antioxidant properties that could reduce oxidative stress damage due to early ischemia and hypoxia of the skin flap in vitro. Moreover, this composite hydrogel attenuated inflammatory responses, promoted angiogenesis, and reduced the distal necrosis of the flap in vivo. Therefore, our hydrogel provides a novel strategy for skin flap graft protection with reduced necrosis and the potential for broad clinical applications.

Chronic nonhealing wounds are serious complications of diabetes with a high morbidity, and they can lead to disability or death. Conventional drug therapy is ineffective for diabetic wound healing because of the complex environment of diabetic wounds and the depth of drug penetration. Here, we developed a self-healing, dual-layer, drug-carrying microneedle (SDDMN) for diabetic wound healing. This SDDMN can realize transdermal drug delivery and broad-spectrum sterilization without drug resistance and meets the multiple needs of the diabetic wound healing process. Quaternary ammonium chitosan cografted with dihydrocaffeic acid (Da) and l-arginine and oxidized hyaluronic acid-dopamine are the main parts of the self-healing hydrogel patch. Methacrylated poly(vinyl alcohol) (methacrylated PVA) and phenylboronic acid (PBA) were used as the main part of the MN, and gallium porphyrin modified with 3-amino-1,2 propanediol (POGa) and insulin were encapsulated at its tip. Under hyperglycaemic conditions, the PBA moiety in the MN reversibly formed a glucose-boronic acid complex that promoted the rapid release of POGa and insulin. POGa is disguised as hemoglobin through a Trojan-horse strategy, which is then taken up by bacteria, allowing it to target bacteria and infected lesions. Based on the synergistic properties of these components, SDDMN-POGa patches exhibited an excellent biocompatibility, slow drug release, and antimicrobial properties. Thus, these patches provide a potential therapeutic approach for the treatment of diabetic wounds.