Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation.

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.

Reactive Oxygen Species (ROS)-Degradable Polymeric Nanoplatform for Hypoxia-Targeted Gene Delivery: Unpacking DNA and Reducing Toxicity.

Smart polymers as ideal gene carriers have drawn increasing attentions due to the effective DNA release once triggered by intrinsic stimuli, as well as reduced cytotoxicity. Herein, a stimulus-responsive, positively charged and water-soluble polymer (OEI-TK x) was facilely engineered by cross-linking low molecular weight oligoethylenimine (OEI) via thioketal (TK) linkages that would cleave selectively in reactive oxygen species (ROS)-rich environments induced by hypoxia. Agarose gel electrophoresis assay demonstrated that the threshold N/P ratios for complete retardation of negatively charged DNA migration were above 5 for OEI-TK x. The reduction in DNA-condensing capability and the changes in particle size, size distribution and particle morphology all illustrated that OEI-TK x possessed excellent ROS responsiveness. OEI-TK x/DNA polyplexes showed lower toxicity and higher gene transfection efficiency compared with PEI/DNA polyplexes. The optimum formulation, OEI-TK x/DNA polyplexes (N/P = 40), showed a little better performance than PEI/DNA polyplexes in cellular uptake profile. Furthermore, OEI-TK x/DNA polyplexes could escape from endosomes to the cytosol as efficiently as PEI/DNA polyplexes. Confocal images confirmed that OEI-TK x/DNA polyplexes could more effectively release DNA than PEI/DNA polyplexes, mainly owing to the valid cleavage of thioketal linkages induced by characteristic rich-ROS in Hela cells. These results suggested that OEI-TK x could represent an on-demand stimulus-responsive gene delivery platform.

Tailoring the Supramolecular Structure of Guanidinylated Pullulan toward Enhanced Genetic Photodynamic Therapy.

In the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions. A zeta potential plateau (∼+23 mV) of OGG3P complexes indicated the nonionic hydrophilic hydroxyl groups in pullulan might neutralize the excessive detrimental cationic charges. There was no obvious cytotoxicity and hemolysis, but also enhancement of transfection efficiency with regard to OGG3P in comparison with that of native G3P in Hela and HEK293T cells. More importantly, we found that the uptake efficiency in Hela cells between OGG3P and G3P complexes was not markedly different. However, guanidination caused changes in uptake pathway and led to macropinocytosis pathway, which may be a crucial reason for improved transfection efficiency. After introducing a therapeutic pKillerRed-mem plasmid, OGG3P complexes achieved significantly enhanced KillerRed protein expression and ROS production under irradiation. ROS-induced cancer cells proliferation suppression was also confirmed. This study highlights the guanidine-decorated dendronized pullulan could emerge as a reliable nonviral gene carrier to specifically deliver therapeutic genes.

Specially-Made Lipid-Based Assemblies for Improving Transmembrane Gene Delivery: Comparison of Basic Amino Acid Residue Rich Periphery.

Cationic lipid based assemblies provide a promising platform for effective gene condensation into nanosized particles, and the peripheral properties of the assemblies are vital for complexation and interaction with physical barriers. Here, we report three cationic twin head lipids, and each of them contains a dioleoyl-glutamate hydrophobic tail and a twin polar head of lysine, arginine, or histidine. Such lipids were proven to self-assemble in aqueous solution with well-defined nanostructures and residual amino-, guanidine-, or imidazole-rich periphery, showing strong buffering capacity and good liquidity. The assemblies with arginine (RL) or lysine (KL) periphery exhibited positive charges (∼+35 mV) and complete condensation of pDNA into nanosized complexes (∼120 nm). In contrast, assemblies composed of histidine-rich lipids (HL) showed relatively low cationic electric potential (∼+10 mV) and poor DNA binding ability. As expected, the designed RL assemblies with guanidine-rich periphery enhanced the in vitro gene transfection up to 190-fold as compared with the golden standard PEI25k and Lipofectamine 2000, especially in the presence of serum. Meanwhile, interaction with cell and endo/lysosome membrane also revealed the superiority of RL complexes, that the guanidine-rich surface efficiently promoted transmembrane process in cellular internalization and endosomal disruption. More importantly, RL complexes also succeeded beyond others in vivo with significantly (∼7-fold) enhanced expression in HepG2 tumor xenografts in mice, as well as stronger green fluorescence protein imaging in isolated tumors and tumor frozen sections.

Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery.

In this study, the amphiphilic fluorinated peptide dendrons functionalized dextran (FPD-HZN-Dex) via an acid-sensitive hydrazone linkage was successfully designed and prepared for the first time. We demonstrated a spontaneous self-assembly of amphiphilic FPD-HZN-Dex into the well-defined nanoparticles with the core-shell architecture in aqueous media, which is attributed to the efficient amphiphilic functionalization of dextran by the hydrophobic fluorinated peptide dendrons. The spherical morphology, uniform particle size and good storage stability of the prepared FPD-HZN-Dex nanoparticles were characterized by dynamic light scattering and transmission electron microscopy, respectively. In vitro drug release studies showed a controlled and pH dependent hydrophobic drug release profile. The cell viability assays show excellent biocompatibility of the FPD-HZN-Dex nanoparticles for both normal cells and tumor cells. Moreover, the FPD-HZN-Dex self-assembled systems based on pH-sensitive hydrazone linkage also can serve as stimulus bioresponsive carriers for on-demand intracellular drug delivery. These self-assembled nanoparticles exhibit a stimulus-induced response to endo/lysosome pH (pH 5.0) that causes their disassembly over time, enabling controlled release of encapsulated DOX. This work has unveiled a unique non-covalent interaction useful for engineering amphiphilic dendrons or dendrimers self-assembled systems.

Nature-Inspired Scarless Healing: Guiding Biomaterials Design for Advanced Therapies.

The use of biomaterials in the treatment of skin wounds has been steadily increasing over the last two decades. The key to the successful application of biomaterials in scar reduction is the up-to-date knowledge of the actors involved in accelerated healing and the cellular factors that can be implemented in bioinspired materials. Natural models of scarless healing such as oral mucosa, fetal skin and the skin of amphibians, fish, and reptiles are a great source of information. By investigating their microenvironments, cellular factors, and inflammatory self-regulatory systems, a general model of scarless healing can be defined. This review introduces the basic and current concepts of skin wound healing and focuses on providing a detailed overview of the main processes of accelerated healing without scarring. The article outlines the common features and key points that develop and promote scar-free healing. The tissues and healing processes of the selected natural models are described individually (tissue organization, structural components, ratios of cellular factors such as Collagen and transforming growth factor and their mechanisms of regulation of inflammation and scar overgrowth). A comparative work of each natural model concerning healing in human skin is included in the discussion. Finally, the patterns identified through the analysis of each model and their differences from normal healing are presented to facilitate the knowledge for the implementation of new treatments.

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5-10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10-8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.

A bidirectional Mendelian randomisation study to evaluate the relationship between body constitution and hearing loss.

Hearing loss and hearing disorders represent possible mediating pathways in the associations between noise exposures and non-auditory health outcomes. In this context, we assessed whether the noise-obesity associations should consider hearing functions as possible mediators and applied Mendelian randomisation (MR) to investigate causal relationships between body constitution and hearing impairments. We obtained genetic associations from publicly available summary statistics from genome-wide association studies in European ancestry adult populations (N= from 210,088 to 360,564) for (i) body constitution: body mass index (BMI), waist circumference (WC) and body fat percentage (BFP), and (ii) hearing loss: sensorineural hearing loss, noise-induced hearing loss, and age-related hearing impairment (ARHI). We employed colocalisation analysis to investigate the genetic associations for BMI and ARHI liability within an FTO locus. We conducted bi-directional MR for the 'forward' (from body constitution to hearing) and 'reverse' directions. We applied the random effects inverse variance-weighted method as the main MR method, with additional sensitivity analyses. Colocalisation analysis suggested that BMI and ARHI shared a causal variant at the FTO gene. We did not find robust evidence for causal associations from body constitution to hearing loss and suggested that some associations may be driven by FTO variants. In the reverse analyses, ARHI was negatively associated with BMI [effect size - 0.22 (95% CI - 0.44 to - 0.01)] and BFP [effect size - 0.23 (95% CI - 0.45 to 0.00)], supporting the notion that ARHI may diminish body constitution. Finally, our data suggest that there is no strong evidence that hearing explains the association between noise exposure and body constitution.

Effects of Chemical Composition on the Shape Memory Property of Poly(dl-lactide-co-trimethylene carbonate) as Self-Morphing Small-Diameter Vascular Scaffolds.

Smart materials have great potential in many biomedical applications, in which biodegradable shape memory polymers (SMPs) can be used as surgical sutures, implants, and stents. Poly(dl-lactide-co-trimethylene carbonate) (PDLLTC) represents one of the promising SMPs and is widely used in biomedical applications. However, the relationship between its shape memory property and chemical structure has not been fully studied and needs further elaboration. In this work, PDLLTC copolymers in different compositions have been synthesized, and their shape memory properties have been investigated. It has been found that the shape memory property is related to the chemical composition and polymeric chain segments. The copolymer with a DLLA/TMC ratio of 75:25 (PDLLTC7525) has been demonstrated with great shape fixation and recovery ratio at human body temperature. Furthermore, PDLLTC7525-based self-morphing small-diameter vascular scaffolds adhered with inner electrospun aligned gelatin/hyaluronic acid (Gel/HA) nanofibers have been constructed, as a merit of its shape memory property. The scaffolds have been demonstrated to facilitate the proliferation and adhesion of endothelial cells on the inner layer. Therefore, PDLLTC with tailorable shape memory properties represents a promising candidate for the development of SMPs, as well as for small-diameter vascular scaffolds construction.

Stepwise Multi-Cross-Linking Bioink for 3D Embedded Bioprinting to Promote Full-Thickness Wound Healing.

The emergence and innovation of three-dimensional (3D) bioprinting provide new development opportunities for tissue engineering and regenerative medicine. However, how to obtain bioinks with both biomimicry and manufacturability remains a great issue in 3D bioprinting. Developing intelligent responsive biomaterials is conducive to break through the current dilemma. Herein, a stepwise multi-cross-linking strategy concerning thermosensitive thiolated Pluronic F127 (PF127-SH) and hyaluronic acid methacrylate (HAMA) is proposed to achieve temperature-controlled 3D embedded bioprinting, specifically pre-cross-linking (Michael addition reaction) at low temperatures (4-20 °C) and subsequently self-assembly (hydrophobic interaction) in a high-temperature (30-37 °C) suspension bath as well as final photo-cross-linking (mainly thiol-ene "click" reaction). The unique stepwise cross-linking mechanism promises the thermosensitive bioink appropriate viscosity at different printing stages, making it possible to print complex structures with excellent shape fidelity and simultaneously maintain the biological activity of cells. In vitro studies reveal that 3D-printed hydrogels are beneficial for enhancing cell viability. Further, in vivo experiments demonstrate that cell-laden printed hydrogels significantly promote wound healing and re-epithelialization by modulating inflammation and accelerating collagen deposition and angiogenesis. Therefore, the proposed stepwise multi-cross-linking strategy is expected to accelerate the development of novel bioinks and promote the clinical applications of 3D bioprinting.

Engineered Hierarchical Microdevices Enable Pre-Programmed Controlled Release for Postsurgical and Unresectable Cancer Treatment.

Drug treatment is required for both resectable and unresectable cancers to strive for any meaningful improvement in patient outcomes. However, the clinical benefit of receiving conventional systemic administrations is often less than satisfactory. Drug delivery systems are preferable substitutes but still fail to meet diverse clinical demands due to the difficulty in programming drug release profiles. Herein, a microfabrication concept, termed "Hierarchical Multiple Polymers Immobilization" (HMPI), is introduced and biodegradable-polymer-based hierarchical microdevices (HMDs) that can pre-program any desired controlled release profiles are engineered. Based on the first-line medication of pancreatic and breast cancer, controlled release of single gemcitabine and the doxorubicin/paclitaxel combination in situ for multiple courses is implemented, respectively. Preclinical models of postsurgical pancreatic, postsurgical breast, and unresectable breast cancer are established, and the designed HMDs are demonstrated as well-tolerable and effective treatments for inhibiting tumor growth, recurrence, and metastasis. The proposed HMPI strategy allows the creation of tailorable and high-resolution hierarchical microstructures for pre-programming controlled release according to clinical medication schedules, which may provide promising alternative treatments for postsurgical and unresectable tumor control.

A facile bioorthogonal chemistry-based reversible to irreversible strategy to surmount the dilemma between injectability and stability of hyaluronic acid hydrogels.

Injectable and stable hydrogels have great promise for clinical applications. Fine-tuning the injectability and the stability of the hydrogels at different stages has been challenging due to the limited number of coupling reactions. A distinct "reversible to irreversible" concept using a thiazolidine-based bioorthogonal reaction between 1,2-aminothiols and aldehydes in physiological conditions to surmount the dilemma between injectability and stability is presented for the first time. Upon mixing aqueous solutions of aldehyde-functionalized hyaluronic acid (SA-HA) and cysteine-capped ethylenediamine (DI-Cys), SA-HA/DI-Cys hydrogels formed through reversible hemithioacetal crosslinking within 2 min. The reversible kinetic intermediate facilitated thiol-triggered gel-to-sol transition, shear-thinning and injectability of the SA-HA/DI-Cys hydrogel but then converted to the irreversible thermodynamic network after injection, thereby permitting the resulting gel with improved stability. As compared to the Schiff base hydrogels, the hydrogels generated from this simple, yet effective concept awarded improved protection to the embedded mesenchymal stem cells and fibroblast during injection, retained the cells homogeneously within the gel, and allowed them further proliferation in vitro and in vivo. There is potential for the proposed approach of "reversible to irreversible" based on thiazolidine chemistry to be applied as a general coupling technique for developing injectable and stable hydrogels for biomedical applications.

Functionalized gelatin-alginate based bioink with enhanced manufacturability and biomimicry for accelerating wound healing.

Three-dimensional (3D) bioprinting is a promising technique to construct heterogeneous architectures that mimic cell microenvironment. However, the current bioinks for 3D bioprinting usually show some limitations, such as low printing accuracy, unsatisfactory mechanical properties and compromised cytocompatibility. Herein, a novel bioink comprising hydroxyphenyl propionic acid-conjugated gelatin and tyramine-modified alginate is developed for printing 3D constructs. The bioink takes advantage of an ionic/covalent intertwined network that combines covalent bonds formed by photo-mediated redox reaction and ionic bonds formed by chelate effect. Benefiting from the thermosensitivity of gelatin and the double-crosslinking mechanism, the developed bioink shows controllable rheological behaviors, enhanced mechanical behavior, improved printing accuracy and structure stability. Moreover, the printed cell-laden hydrogels exhibit a homogeneous cell distribution and considerable cell survival because the pre-crosslinking of the bioink prevents cellular sedimentation and the visible light crosslinking mechanism preserves cell viability. Further in vivo studies demonstrate that resulting cell-laden hydrogels are beneficial for the reduction of inflammation response and the promotion of collagen deposition and angiogenesis, thereby improving the quality of skin wound healing. This convenient and effective strategy is of great significance for accelerating the development of multifunctional bioinks and broadening the biomedical applications of 3D bioprinting.

Post-synthetic modification (PSM) of MOFs with an ionic polymer for efficient adsorptive removal of methylene blue from water.

UiO-66-NH2 was functionalized with an ionic polymer poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS) through a post-synthetic modification (PSM) strategy. Due to the excellent dispersibility in water and the existence of abundant active binding sites, the obtained UiO-66-PAMPS shows significantly improved adsorption capability toward methylene blue (MB) in aqueous solution.

Improved intracellular delivery of exosomes by surface modification with fluorinated peptide dendrimers for promoting angiogenesis and migration of HUVECs.

Exosomes exhibit great potential as novel therapeutics for tissue regeneration, including cell migration and angiogenesis. However, the limited intracellular delivery efficiency of exosomes might reduce their biological effects. Here, exosomes secreted by adipose-derived mesenchymal stem cells were recombined with fluorinated peptide dendrimers (FPG3) to form the fluorine-engineered exosomes (exo@FPG3), which was intended to promote the cytosolic release and the biological function of exosomes. The mass ratio of FPG3 to exosomes at 5 was used to investigate its cellular uptake efficiency and bioactivity in HUVECs, as the charge of exo@FPG3 tended to be stable even more FPG3 was applied. It was found that exo@FPG3 could enter HUVECs through a variety of pathways, in which the clathrin-mediated endocytosis played an important role. Compared with exosomes modified with peptide dendrimers (exo@PG3) and exosomes alone, the cellular uptake efficiency of exo@FPG3 was significantly increased. Moreover, exo@FPG3 significantly enhanced the angiogenesis and migration of HUVECs in vitro as compared to exo@PG3 and exosomes. It is concluded that surface fluorine modification of exosomes with FPG3 is conducive to the cellular uptake and bioactivity of the exosome, which provides a novel strategy for engineered exosomes to enhance the biological effects of exosome-based drug delivery.

Bioactive hydrogels based on polysaccharides and peptides for soft tissue wound management.

Due to their inherent and tunable biomechanical and biochemical performances, bioactive hydrogels based on polysaccharides and peptides have shown attractive potential for wound management. In this review, the recent progress of bioactive hydrogels prepared by polysaccharides and peptides for soft tissue wound management is overviewed. Meanwhile, we focus on the elaboration of the relationship between chemical structures and inherent bioactive functions of polysaccharides and peptides, as well as the strategies that are taken for achieving multiple wound repairing effects including hemostasis, adhesion, wound contraction and closure, anti-bacteria, anti-oxidation, immunomodulation, molecule delivery, etc. Some innovative and important works are well introduced as well. In the end, current study limitations, clinical unmet needs, and future directions are discussed.

Biodegradable gemcitabine-loaded microdevice with sustained local drug delivery and improved tumor recurrence inhibition abilities for postoperative pancreatic tumor treatment.

At present, the 10-year survival rate of patients with pancreatic cancer is still less than 4%, mainly due to the high cancer recurrence rate caused by incomplete surgery and lack of effective postoperative adjuvant treatment. Systemic chemotherapy remains the only choice for patients after surgery; however, it is accompanied by off-target effects and server systemic toxicity. Herein, we proposed a biodegradable microdevice for local sustained drug delivery and postoperative pancreatic cancer treatment as an alternative and safe option. Biodegradable poly(l-lactic-co-glycolic acid) (P(L)LGA) was developed as the matrix material, gemcitabine hydrochloride (GEM·HCl) was chosen as the therapeutic drug and polyethylene glycol (PEG) was employed as the drug release-controlled regulator. Through adjusting the amount and molecular weight of PEG, the controllable degradation of matrix and the sustained release of GEM·HCl were obtained, thus overcoming the unstable drug release properties of traditional microdevices. The drug release mechanism of microdevice and the regulating action of PEG were studied in detail. More importantly, in the treatment of the postoperative recurrence model of subcutaneous pancreatic tumor in mice, the microdevice showed effective inhibition of postoperative in situ recurrences of pancreatic tumors with excellent biosafety and minimum systemic toxicity. The microdevice developed in this study provides an option for postoperative adjuvant pancreatic treatment, and greatly broadens the application prospects of traditional chemotherapy drugs.

Multifunctional polysaccharide hydrogels for skin wound healing prepared by photoinitiator-free crosslinking.

Photocrosslinked hydrogels show great potential as dressings for skin wound healing. However, most current hydrogels suffer from poor adhesion, toxic photoinitiators, and insufficient versatility. Therefore, developing novel hydrogel dressings with appropriate properties is of great importance to accelerate the wound healing process. In this study, we developed a polysaccharide-based dual-network hydrogel consisting of azide-functionalized carboxymethyl chitosan and o-nitrobenzyl-modified hyaluronic acid (CMC-AZ/HA-NB). The hydrogel showed excellent mechanical, tissue adhesion, and water retention properties. Controllable in situ photocrosslinking was carried out without photoinitiator, avoiding issues associated with the cytotoxicity of photoinitiators. An antibacterial agent-loaded hydrogel (CMC-AZ/HA-NB@D) showed enhanced antibacterial properties. In addition, the CMC-AZ/HA-NB@D hydrogel promoted collagen deposition and vascular formation, as well as reducing the expression of pro-inflammatory factors, thereby accelerating the wound healing process and improving skin regeneration. The present results highlight the promising potential of multifunctional photoinitiator-free polysaccharide hydrogels for application in wound dressings.

Gallium(III)-Mediated Dual-Cross-Linked Alginate Hydrogels with Antibacterial Properties for Promoting Infected Wound Healing.

The metal gallium has enormous promise in fighting infections by disrupting bacterial iron metabolism via a "Trojan horse" trick. It is well worth trying to study the potential of gallium-mediated hydrogel for treating infected wounds. Herein, on the basis of a conventional gelation strategy of sodium alginate combined with metal ions, Ga3+ has been innovatively given a dual role in a dual-cross-linked hydrogel. It acts nor only as a cross-linking agent to form a hydrogel material but also as a therapeutic agent to slow-release and continuously treat infected wounds. Further photo-cross-linking is introduced to improve the mechanical properties of the hydrogel. Thus, a new gallium ionic- and photo-dual-cross-linked alginate hydrogel, with broad-spectrum antimicrobial activity and strengthened mechanical performance, for the treatment of infected wounds is reported. The morphology, degradability, swelling behavior, rheological properties, and gallium release kinetics together indicated the homogeneous and the strengthened mechanical performance of this hydrogel but did not impede the release of gallium ions. Interestingly, in vitro and in vivo results also demonstrated its favorable biocompatibility, reduced bacterial growth, and accelerated infected wound healing, making the gallium-incorporated hydrogel an ideal antimicrobial dressing.

A Dual-Bioinspired Tissue Adhesive Based on Peptide Dendrimer with Fast and Strong Wet Adhesion.

Although tissue adhesives have potential advantages over traditional sutures, existing ones suffer from several limitations: slow adhesion kinetic, low mechanical strength, and poor interfacial bonding with wet biological tissues. Herein, a cooperative mussel/slug double-bioinspired hydrogel adhesive (DBHA) composed of a robust adhesive interface and a stretchable dissipative matrix is developed. The DBHA is formed by a cationic polysaccharide (chitosan), an anionic polysaccharide (carboxymethyl cellulose), and a barbell-like dendritic lysine grafted with catechol groups (G3KPCA). Compared to various commercial bio-glues and traditional adhesives, the DBHA has significantly stronger tissue adhesion and enhanced toughness both ex vivo and in vivo. Meanwhile, the DBHA exhibits fast, strong, tough, and durable adhesion to diverse ex vivo tissue surfaces with blood. The adhesion energy between the adhesive and porcine skin can reach 200-900 J m-2 . Additionally, in vivo studies prove that DBHA has good hemostasis of rabbit artery trauma and achieves better wound healing of tissue incision than commercial bio-glues. This study provides a novel strategy for fabricating fast and strong wet adhesives, which can be used in many applications, such as soft robots, tissue adhesives and hemostats.