Oral exosome-like nanovesicles from Phellinus linteus suppress metastatic hepatocellular carcinoma by reactive oxygen species generation and microbiota rebalancing.

The biomedical application of nanotechnology in cancer treatment has demonstrated significant potential for improving treatment efficiencies and ameliorating adverse effects. However, the medical translation of nanotechnology-based nanomedicines faces challenges including hazardous environmental effects, difficulties in large-scale production, and possible excessive costs. In the present study, we extracted and purified natural exosome-like nanoparticles (ELNs) from Phellinus linteus. These nanoparticles (denoted as P-ELNs) had an average particle size of 154.1 nm, displayed a negative zeta potential of -31.3 mV, and maintained stability in the gastrointestinal tract. Furthermore, P-ELNs were found to contain a diverse array of functional components, including lipids and pharmacologically active small-molecule constituents. In vitro investigations suggested that they exhibited high internalization efficiency in liver tumor cells (Hepa 1-6) and exerted significant anti-proliferative, anti-migratory, and anti-invasive effects against Hepa 1-6 cells. Strikingly, the therapeutic outcomes of oral P-ELNs were confirmed in an animal model of metastatic hepatocellular carcinoma by amplifying reactive oxygen species (ROS) and rebalancing the gut microbiome. These findings demonstrate the potential of P-ELNs as a promising oral therapeutic platform for liver cancer treatment.

Magnetic natural lipid nanoparticles for oral treatment of colorectal cancer through potentiated antitumor immunity and microbiota metabolite regulation.

The therapeutic efficacy of oral nanotherapeutics against colorectal cancer (CRC) is restricted by inadequate drug accumulation, immunosuppressive microenvironment, and intestinal microbiota imbalance. To overcome these challenges, we elaborately constructed 6-gingerol (Gin)-loaded magnetic mesoporous silicon nanoparticles and functionalized their surface with mulberry leaf-extracted lipids (MLLs) and Pluronic F127 (P127). In vitro experiments revealed that P127 functionalization and alternating magnetic fields (AMFs) promoted internalization of the obtained P127-MLL@Gins by colorectal tumor cells and induced their apoptosis/ferroptosis through Gin/ferrous ion-induced oxidative stress and magneto-thermal effect. After oral administration, P127-MLL@Gins safely passed to the colorectal lumen, infiltrated the mucus barrier, and penetrated into the deep tumors under the influence of AMFs. Subsequently, the P127-MLL@Gin (+ AMF) treatment activated antitumor immunity and suppressed tumor growth. We also found that this therapeutic modality significantly increased the abundance of beneficial bacteria (e.g., Bacillus and unclassified-c-Bacilli), reduced the proportions of harmful bacteria (e.g., Bacteroides and Alloprevotella), and increased lipid oxidation metabolites. Strikingly, checkpoint blockers synergistically improved the therapeutic outcomes of P127-MLL@Gins (+ AMF) against orthotopic and distant colorectal tumors and significantly prolonged mouse life spans. Overall, this oral therapeutic platform is a promising modality for synergistic treatment of CRC.

Decellularized Placental Sponge: A Platform for Coculture of Mesenchymal Stem Cells/Macrophages to Assess an M2 Phenotype and Osteogenic Differentiation In Vitro and In Vivo.

Effective communication between immune and bone-forming cells is crucial for the successful healing of bone defects. This study aimed to assess the potential of a decellularized placental sponge (DPS) as a coculture system for inducing M1/M2 polarization in macrophages and promoting osteogenic differentiation in adipose-derived mesenchymal stem cells (AD-MSCs), both in vitro and in vivo. We prepared the DPS and conducted a comprehensive characterization of its biomechanical properties, antibacterial activity, and biocompatibility. In vitro, we examined the influence of the DPS on the polarization of macrophages cocultured with AD-MSCs through nitric oxide assays, cytokine assays, phagocytosis tests, and real-time polymerase chain reaction (PCR). For in vivo assessment, we utilized micro-CT imaging, histological evaluations, and real-time PCR to determine the impact of the DPS seeded with Wharton's jelly mesenchymal stem cells (WJ-MSCs) on bone regeneration in a calvarial bone defect model. The coculture of AD-MSCs and macrophages on the DPS led to increased production of IL-10, upregulation of CD206, Arg1, and YM1 gene expression, and enhanced phagocytic capacity for apoptotic thymocytes. Concurrently, it reduced the secretion of TNF-α and nitric oxide (NO), downregulated the expression of CD86, NOS2, and IRF5 genes, and decreased macrophage phagocytosis of yeast. These results indicated polarization of macrophages toward an M2-like phenotype. In vivo, the presence of the DPS resulted in enhanced bone formation at the defect site. Immunostaining demonstrated that both the DPS and DPS + WJ-MSC constructs induced macrophage polarization toward an M2 phenotype, as compared to the control defect. In conclusion, this immunomodulatory effect, coupled with its biocompatibility and biomechanical properties resembling natural bone, positions the DPS as an attractive candidate for further exploration in the field of bone tissue engineering and regenerative medicine.

Evaluation of novel dendrimer-gold complex nanoparticles for theranostic application in oncology.

Aim: Despite some successful examples of therapeutic nanoparticles reaching clinical stages, there is still a significant need for novel formulations in order to improve the selectivity and efficacy of cancer treatment. Methods: The authors developed two novel dendrimer-gold (Au) complex-based nanoparticles using two different synthesis routes: complexation method (formulation A) and precipitation method (formulation B). Using a biomimetic cancer-on-a-chip model, the authors evaluated the possible cytotoxicity and internalization by colorectal cancer cells of dendrimer-Au complex-based nanoparticles. Results: The results showed promising capabilities of these nanoparticles for selectively targeting cancer cells and delivering drugs, particularly for the formulation A nanoparticles. Conclusion: This work highlights the potential of dendrimer-Au complex-based nanoparticles as a new strategy to improve the targeting of anticancer drugs.

An Oral Nanomedicine Elicits In Situ Vaccination Effect against Colorectal Cancer.

Oral administration is the most preferred approach for treating colon diseases, and in situ vaccination has emerged as a promising cancer therapeutic strategy. However, the lack of effective drug delivery platforms hampered the application of in situ vaccination strategy in oral treatment of colorectal cancer (CRC). Here, we construct an oral core-shell nanomedicine by preparing a silk fibroin-based dual sonosensitizer (chlorin e6, Ce6)- and immunoadjuvant (imiquimod, R837)-loaded nanoparticle as the core, with its surface coated with plant-extracted lipids and pluronic F127 (p127). The resultant nanomedicines (Ce6/R837@Lp127NPs) maintain stability during their passage through the gastrointestinal tract and exert improved locomotor activities under ultrasound irradiation, achieving efficient colonic mucus infiltration and specific tumor penetration. Thereafter, Ce6/R837@Lp127NPs induce immunogenic death of colorectal tumor cells by sonodynamic treatment, and the generated neoantigens in the presence of R837 serve as a potent in situ vaccine. By integrating with immune checkpoint blockades, the combined treatment modality inhibits orthotopic tumors, eradicates distant tumors, and modulates intestinal microbiota. As the first oral in situ vaccination, this work spotlights a robust oral nanoplatform for producing a personalized vaccine against CRC.

Tissue adhesives based on chitosan for skin wound healing: Where do we stand in this era? A review.

Chitosan has been commonly used as an adhesive dressing material due to its excellent biocompatibility, degradability, and renewability. Tissue adhesives are outstanding among wound dressings because they can close the wound, absorb excess tissue exudate from the wound site, provide a moist environment, and act as a carrier for loading various bioactive molecules. They have been widely used in both preclinical and clinical treatment of skin wounds. This review summarizes recent research progresses in the application of chitosan and its derivatives for tissue adhesives. We also introduce their biomedical effects on wound adhesion, contamination isolation, antibacterial, immune regulation, and wound healing, and the strategies to achieve these functions when used as wound dressings. Finally, challenges and future perspectives of chitosan-based tissue adhesives are discussed for wound healing.

Natural lipid nanoparticles extracted from Morus nigra L. leaves for targeted treatment of hepatocellular carcinoma via the oral route.

The clinical application of conventional medications for hepatocellular carcinoma treatment has been severely restricted by their adverse effects and unsatisfactory therapeutic effectiveness. Inspired by the concept of 'medicine food homology', we extracted and purified natural exosome-like lipid nanoparticles (LNPs) from black mulberry (Morus nigra L.) leaves. The obtained MLNPs possessed a desirable hydrodynamic particle size (162.1 nm), a uniform size distribution (polydispersity index = 0.025), and a negative surface charge (-26.6 mv). These natural LNPs were rich in glycolipids, functional proteins, and active small molecules (e.g., rutin and quercetin 3-O-glucoside). In vitro experiments revealed that MLNPs were preferentially internalized by liver tumor cell lines via galactose receptor-mediated endocytosis, increased intracellular oxidative stress, and triggered mitochondrial damage, resulting in suppressing the viability, migration, and invasion of these cells. Importantly, in vivo investigations suggested that oral MLNPs entered into the circulatory system mainly through the jejunum and colon, and they exhibited negligible adverse effects and superior anti-liver tumor outcomes through direct tumor killing and intestinal microbiota modulation. These findings collectively demonstrate the potential of MLNPs as a natural, safe, and robust nanomedicine for oral treatment of hepatocellular carcinoma.

Mulberry Leaf Lipid Nanoparticles: a Naturally Targeted CRISPR/Cas9 Oral Delivery Platform for Alleviation of Colon Diseases.

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

Transient Mild Photothermia Improves Therapeutic Performance of Oral Nanomedicines with Enhanced Accumulation in the Colitis Mucosa.

The treatment outcomes of oral medications against ulcerative colitis (UC) have long been restricted by low drug accumulation in the colitis mucosa and subsequent unsatisfactory therapeutic efficacy. Here, high-performance pluronic F127 (P127)-modified gold shell (AuS)-polymeric core nanotherapeutics loading with curcumin (CUR) is constructed. Under near-infrared irradiation, the resultant P127-AuS@CURs generate transient mild photothermia (TMP; ≈42 °C, 10 min), which facilitates their penetration through colonic mucus and favors multiple cellular processes, including cell internalization, lysosomal escape, and controlled CUR release. This strategy relieves intracellular oxidative stress, improves wound healing, and reduces immune responses by polarizing the proinflammatory M1-type macrophages to the anti-inflammatory M2-type. Upon oral administration of hydrogel-encapsulating P127-AuS@CURs plus intestinal intralumen TMP, their therapeutic effects against acute and chronic UC are demonstrated to be superior to those of a widely used clinical drug, dexamethasone. The treatment of P127-AuS@CURs (+ TMP) elevates the proportions of beneficial bacteria (e.g., Lactobacillus and Lachnospiraceae), whose metabolites can also mitigate colitis symptoms by regulating genes associated with antioxidation, anti-inflammation, and wound healing. Overall, the intestinal intralumen TMP offers a promising approach to enhance the therapeutic outcomes of noninvasive medicines against UC.

Facilely printed silk fibroin hydrogel microparticles as injectable long-lasting fillers.

There is a high demand from aging people for facial fillers with desirable biocompatibility and lasting filling effects to overcome facial depression. Novel injectable regenerated silk fibroin (RSF) microparticles were facilely printed from a glycidyl methacrylate-modified silk fibroin hydrogel to address this issue. The ß-sheet content and mechanical properties of the RSF hydrogel can be simply modulated by the number of freeze-thawing cycles, and the swelling rate of the RSF hydrogel in saline was negligible. The printed RSF microparticles were uniform, and their diameter was about 300-500 µm, which could be adjusted by the pore sizes of the printed screens. After the injection with a 26-gauge needle, the size distribution of RSF microparticles had no noticeable variation, suggesting that the microparticles could bear the shear strain without breaking during the injection. The in vitro experiments demonstrated that RSF not only had desirable biocompatibility but also facilitated fibroblast migration. The subcutaneous injection experiments demonstrated that the RSF microparticles formed a lasting spot in the injected site. The tissue sections revealed that the RSF microparticles were still distinct on week 8, and blood vessels formed around the microparticles. These promising data demonstrate that the printed RSF microparticles have great potential for facial rejuvenation.

Transparent silk fibroin film-facilitated infected-wound healing through antibacterial, improved fibroblast adhesion and immune modulation.

The clinical application of regenerated silk fibroin (RSF) films for wound treatment is restricted by its undesirable mechanical properties and lack of antibacterial activity. Herein, different pluronic polymers were introduced to optimize their mechanical properties and the RSF film with 2.5% pluronic F127 (RSFPF127) stood out to address the above issues owing to its satisfactory mechanical properties, hydrophilicity, and transmittance. Diverse antibacterial agents (curcumin, Ag nanoparticles, and antimicrobial peptide KR-12) were separately encapsulated in RSFPF127 to endow it with antibacterial activity. In vitro experiments revealed that the medicated RSFPF127 could persistently release drugs and had desirable bioactivities toward killing bacteria, promoting fibroblast adhesion, and modulating macrophage polarization. In vivo experiments revealed that medicated RSFPF127 not only eradicated methicillin-resistant Staphylococcus aureus in the wound area and inhibited inflammatory responses, but also facilitated angiogenesis and re-epithelialization, regardless of the types of antibacterial agents, thus accelerating the recovery of infected wounds. These results demonstrate that RSFPF127 is an ideal matrix platform to load different types of drugs for application as wound dressings.

CaO2-Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation.

During the wound tissue healing process, the relatively weak driving forces of tissue barriers and concentration gradients lead to a slow and inefficient penetration of bioactive substances into the wound area, consequently showing an impact on the effectiveness of deep wound healing. To overcome these challenges, we constructed biocompatible CaO2-Cu2O "micromotors". These micromotors reacted with the fluids at the wound site, releasing oxygen bubbles and propelling particles deep into the wound tissue. In vitro experimental results revealed that these micromotors not only exhibited antibacterial and hemostatic functions but also facilitated the migration of dermal fibroblasts and vascular endothelial cells, while modulating the inflammatory microenvironment. A methicillin-resistant Staphylococcus aureus infected full-thickness-wound model was created in rats, in which CaO2-Cu2O micromotors markedly expedited the wound healing process. Specifically, CaO2-Cu2O provided a sterile microenvironment for wounds and increased the amounts of M1-type macrophages during infection and inflammation. During the proliferation and remodeling stages, the amount of M1 macrophages gradually decreased, while the amount of M2 macrophages increased, and CaO2-Cu2O did not prolong the inflammatory period. Furthermore, the introduction of a regenerated silk fibroin (RSF) film on the wound surface successfully enhanced the therapeutic effects of CaO2-Cu2O against the infected wound. The combined application of oxygen-producing CaO2-Cu2O micromotors and a RSF film demonstrates significant therapeutic potential and emerges as a promising candidate for the treatment of infected wounds.

Smart Responsive Microneedles for Controlled Drug Delivery.

As an emerging technology, microneedles offer advantages such as painless administration, good biocompatibility, and ease of self-administration, so as to effectively treat various diseases, such as diabetes, wound repair, tumor treatment and so on. How to regulate the release behavior of loaded drugs in polymer microneedles is the core element of transdermal drug delivery. As an emerging on-demand drug-delivery technology, intelligent responsive microneedles can achieve local accurate release of drugs according to external stimuli or internal physiological environment changes. This review focuses on the research efforts in smart responsive polymer microneedles at home and abroad in recent years. It summarizes the response mechanisms based on various stimuli and their respective application scenarios. Utilizing innovative, responsive microneedle systems offers a convenient and precise targeted drug delivery method, holding significant research implications in transdermal drug administration. Safety and efficacy will remain the key areas of continuous efforts for research scholars in the future.

Dual-driven nanomotors enable tumor penetration and hypoxia alleviation for calcium overload-photo-immunotherapy against colorectal cancer.

The treatment efficacies of conventional medications against colorectal cancer (CRC) are restricted by a low penetrative, hypoxic, and immunosuppressive tumor microenvironment. To address these restrictions, we developed an innovative antitumor platform that employs calcium overload-phototherapy using mitochondrial N770-conjugated mesoporous silica nanoparticles loaded with CaO2 (CaO2-N770@MSNs). A loading level of 14.0 wt% for CaO2-N770@MSNs was measured, constituting an adequate therapeutic dosage. With the combination of oxygen generated from CaO2 and hyperthermia under near-infrared irradiation, CaO2-N770@MSNs penetrated through the dense mucus, accumulated in the colorectal tumor tissues, and inhibited tumor cell growth through endoplasmic reticulum stress and mitochondrial damage. The combination of calcium overload and phototherapy revealed high therapeutic efficacy against orthotopic colorectal tumors, alleviated the immunosuppressive microenvironment, elevated the abundance of beneficial microorganisms (e.g., Lactobacillaceae and Lachnospiraceae), and decreased harmful microorganisms (e.g., Bacteroidaceae and Muribaculaceae). Moreover, together with immune checkpoint blocker (αPD-L1), these nanoparticles showed an ability to eradicate both orthotopic and distant tumors, while potentiating systemic antitumor immunity. This treatment platform (CaO2-N770@MSNs plus αPD-L1) open a new horizon of synergistic treatment against hypoxic CRC with high killing power and safety.

Trapping metastatic cancer cells with mechanical ratchet arrays.

Current treatments for cancer, such as chemotherapy, radiotherapy, immunotherapy, and surgery, have positive results but are generally ineffective against metastatic tumors. Treatment effectiveness can be improved by employing bioengineered cancer traps, typically utilizing chemoattractant-loaded materials, to attract infiltrating cancer cells preventing their uncontrolled spread and potentially enabling eradication. However, the encapsulated chemical compounds can have adverse effects on other cells causing unwanted responses, and the generated gradients can evolve unpredictably. Here, we report the development of a cancer trap based on mechanical ratchet structures to capture metastatic cells. The traps use an array of asymmetric local features to mechanically attract cancer cells and direct their migration for prolonged periods. The trapping efficiency was found to be greater than isotropic or inverse anisotropic ratchet structures on either disseminating cancer cells and tumor spheroids. Importantly, the traps exhibited a reduced effectiveness when targeting non-metastatic and non-tumorigenic cells, underscoring their particular suitability for capturing highly invasive cancer cells. Overall, this original approach may have therapeutic implications for fighting cancer, and may also be used to control cell motility for other biological processes. STATEMENT OF SIGNIFICANCE: Current cancer treatments have limitations in treating metastatic tumors, where cancer cells can invade distant organs. Biomaterials loaded with chemoattractants can be implanted to attract and capture metastatic cells preventing uncontrolled spread. However, encapsulated chemical compounds can have adverse effects on other cells, and gradients can evolve unpredictably. This paper presents an original concept of "cancer traps" based on using mechanical ratchet-based structures to capture metastatic cancer cells, with greater trapping efficiency and stability than previously studied methods. This innovative approach has significant potential clinical implications for fighting cancer, particularly in treating metastatic tumors. Additionally, it could be applied to control cell motility for other biological processes, opening new possibilities for biomedicine and tissue engineering.

Mulberry Biomass-Derived Nanomedicines Mitigate Colitis through Improved Inflamed Mucosa Accumulation and Intestinal Microenvironment Modulation.

The therapeutic outcomes of conventional oral medications against ulcerative colitis (UC) are restricted by inefficient drug delivery to the colitis mucosa and weak capacity to modulate the inflammatory microenvironment. Herein, a fluorinated pluronic (FP127) was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles (MLNs) loading with resveratrol nanocrystals (RNs). The obtained FP127@RN-MLNs possessed exosome-like morphologies, desirable particle sizes (around 171.4 nm), and negatively charged surfaces (-14.8 mV). The introduction of FP127 to RN-MLNs greatly improved their stability in the colon and promoted their mucus infiltration and mucosal penetration capacities due to the unique fluorine effect. These MLNs could efficiently be internalized by colon epithelial cells and macrophages, reconstruct disrupted epithelial barriers, alleviate oxidative stress, provoke macrophage polarization to M2 phenotype, and down-regulate inflammatory responses. Importantly, in vivo studies based on chronic and acute UC mouse models demonstrated that oral administration of chitosan/alginate hydrogel-embedding FP127@RN-MLNs achieved substantially improved therapeutic efficacies compared with nonfluorinated MLNs and a first-line UC drug (dexamethasone), as evidenced by decreased colonic and systemic inflammation, integrated colonic tight junctions, and intestinal microbiota balance. This study brings new insights into the facile construction of a natural, versatile nanoplatform for oral treatment of UC without adverse effects.

3D-printed placental-derived bioinks for skin tissue regeneration with improved angiogenesis and wound healing properties.

Extracellular matrix (ECM)-based bioinks has attracted much attention in recent years for 3D printing of native-like tissue constructs. Due to organ unavailability, human placental ECM can be an alternative source for the construction of 3D print composite scaffolds for the treatment of deep wounds. In this study, we use different concentrations (1.5%, 3% and 5%w/v) of ECM derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin. The printed hydrogels' morphology, physical structure, mechanical behavior, biocompatibility, and angiogenic property are investigated. The optimized ECM (5%w/v) 3D printed scaffold is applied on full-thickness wounds created in a mouse model. Due to their unique native-like structure, the ECM-based scaffolds provide a non-cytotoxic microenvironment for cell adhesion, infiltration, angiogenesis, and proliferation. In contrast, they do not show any sign of immune response to the host. Notably, the biodegradation, swelling rate, mechanical property, cell adhesion and angiogenesis properties increase with the increase of ECM concentrations in the construct. The ECM 3D printed scaffold implanted into deep wounds increases granulation tissue formation, angiogenesis, and re-epithelialization due to the presence of ECM components in the construct, when compared with printed scaffold with no ECM and no treatment wound. Overall, our findings demonstrate that the 5% ECM 3D scaffold supports the best deep wound regeneration in vivo, produces a skin replacement with a cellular structure comparable to native skin.

Manipulating supramolecular gels with surfactants: Interfacial and non-interfacial mechanisms.

Gel is a class of self-supporting soft materials with applications in many fields. Fast, controllable gelation, micro/nano structure and suitable rheological properties are essential considerations for the design of gels for specific applications. Many methods can be used to control these parameters, among which the additive approach is convenient as it is a simple physical mixing process with significant advantages, such as avoidance of pH change and external energy fields (ultrasound, UV light and others). Although surfactants are widely used to control the formation of many materials, particularly nanomaterials, their effects on gelation are less known. This review summarizes the studies that utilized different surfactants to control the formation, structure, and properties of molecular and silk fibroin gels. The mechanisms of surfactants, which are interfacial and non-interfacial effects, are classified and discussed. Knowledge and technical gaps are identified, and perspectives for further research are outlined. This review is expected to inspire increasing research interest in using surfactants for designing/fabricating gels with desirable formation kinetics, structure, properties and functionalities.

Electro-responsive silk fibroin microneedles for controlled release of insulin.

To date, very limited work has been done on convenient and active control of insulin release. Herein, we report an electro-responsive insulin delivery system based on thiolated silk fibroin. The disulfide cross-linking points in TSF were reduced and broken to form sulfhydryl groups under electrification, which led to the increase of microneedle swelling degree and promoted insulin release. After power failure, the sulfhydryl group is oxidised to form disulfide bond crosslinking point again, resulting in the reduction of microneedle swelling degree and thus the reduction of release rate. The insulin loaded in the electro-responsive insulin delivery system showed good reversible electroresponsive release performance. The addition of graphene reduced the microneedle resistance and increased the drug release rate under current conditions. In vivo studies on type 1 diabetic mice show that electro-responsive insulin delivery system effectively controls the blood glucose before and after feeding by switching on and off the power supply, and this blood glucose control can be maintained within the safe range (100-200 mg/dL) for a long time (11h). Such electrically responsive delivery microneedles show potential for integration with glucose signal monitoring and are expected to build closed-loop insulin delivery systems.

Bioinspired Polyacrylic Acid-Based Dressing: Wet Adhesive, Self-Healing, and Multi-Biofunctional Coacervate Hydrogel Accelerates Wound Healing.

Polyacrylic acid (PAA) and its derivatives are commonly used as essential matrices in wound dressings, but their weak wet adhesion restricts the clinical application. To address this issue, a PAA-based coacervate hydrogel with strong wet adhesion capability is fabricated through a facile mixture of PAA copolymers with isoprenyl oxy poly(ethylene glycol) ether and tannic acid (TA). The poly(ethylene glycol) segments on PAA prevent the electrostatic repulsion among the ionized carboxyl groups and absorbed TA to form coacervates. The absorbed TA provides solid adhesion to dry and wet substrates via multifarious interactions, which endows the coacervate with an adhesive strength to skin of 23.4 kPa and 70% adhesion underwater. This coacervate achieves desirable self-healing and extensible properties suitable for frequently moving joints. These investigations prove that the coacervate has strong antibacterial activity, facilitates fibroblast migration, and modulates M1/M2 polarization of macrophages. In vivo hemorrhage experiments further confirm that the coacervate dramatically shortens the hemostatic time from hundreds to tens of seconds. In addition, full-thickness skin defect experiments demonstrate that the coacervate achieves the best therapeutic effect by significantly promoting collagen deposition, angiogenesis, and epithelialization. These results demonstrate that a PAA-based coacervate hydrogel is a promising wound dressing for medical translation.