Swift Covalent Gelation Coupled with Robust Wet Adhesive Powder: A Novel Approach for Acute Massive Hemorrhage Control in Dynamic and High-Pressure Wound Environments.

The quest for efficient hemostatic agents in emergency medicine is critical, particularly for managing massive hemorrhages in dynamic and high-pressure wound environments. Traditional self-gelling powders, while beneficial due to their ease of application and rapid action, fall short in such challenging conditions. To bridge this gap, the research introduces a novel self-gelling powder that combines ultrafast covalent gelation and robust wet adhesion, presenting a significant advancement in acute hemorrhage control. This ternary system comprises ε-polylysine (ε-PLL) and 4-arm polyethylene glycol succinyl succinate (4-arm-PEG-NHS) forming the hydrogel framework. Na2HPO4 functions as the "H+ sucker" to expedite the amidation reaction, slashing gelation time to under 10 s, crucial for immediate blood loss restriction. Moreover, PEG chains' hydrophilicity facilitates efficient absorption of interfacial blood, increasing the generated hydrogel's cross-linking density and strengthens its tissue bonding, thereby resulting in excellent mechanical and wet adhesion properties. In vitro experiments reveal the optimized formulation's exceptional tissue compliance, procoagulant activity, biocompatibility and antibacterial efficacy. In porcine models of heart injuries and arterial punctures, it outperforms commercial hemostatic agent Celox, confirming its rapid and effective hemostasis. Conclusively, this study presents a transformative approach to hemostasis, offering a reliable and potent solution for the emergency management of massive hemorrhage.

Materiobiomodulated ROS Therapy for De Novo Hair Growth.

Hair loss is characterized by the inability of hair follicles (HFs) to enter the telogen-anagen transition (TAT) and lack of de novo HFs. Current pharmaceutical therapies and surgical modalities have been largely limited to regulating hair regrowth efficiently without side effects and lacking treatment compliance. Here, this work proposes a materiobiomodulation therapy (MBMT), wherein polydopamine (PDA) nanoparticles with redox activity can be modulated to have a stoichiometric ROS (H2O2) donating ability. These nanoparticles can intracellularly deliver ROS with high-efficiency via the clathrin-dependent endocytosis process. Utilizing homozygote transgenic HyPerion (a genetically-encoded H2O2 biosensor) mice, this work also achieves in vivo dynamic monitoring of intracellular H2O2 elevation induced by ROS donators. Subcutaneous administration with ROS donators results in rapid onset of TAT and subsequent hair regrowth with a specific ROS "hormesis effect." Mechanistically, ROS activate ß-catenin-dependent Wnt signaling, upregulating hair follicle stem cell expression. This work further develops a microneedles patch for transdermal ROS delivery, demonstrating long-term, low-dose ROS release. Unlike photobiomodulation therapy (PBMT), MBMT requires no external stimuli, providing a convenient and efficient approach for clinical hair loss treatment. This material-HF communication implicates new avenues in HF-related diseases, achieving targeted ROS delivery with minimal side effects.

Programmable Electro-Assembly of Collagen: Constructing Porous Janus Films with Customized Dual Signals for Immunomodulation and Tissue Regeneration in Periodontitis Treatment.

Currently available guided bone regeneration (GBR) films lack active immunomodulation and sufficient osteogenic ability- in the treatment of periodontitis, leading to unsatisfactory treatment outcomes. Challenges remain in developing simple, rapid, and programmable manufacturing methods for constructing bioactive GBR films with tailored biofunctional compositions and microstructures. Herein, the controlled electroassembly of collagen under the salt effect is reported, which enables the construction of porous films with precisely tunable porous structures (i.e., porosity and pore size). In particular, bioactive salt species such as the anti-inflammatory drug diclofenac sodium (DS) can induce and customize porous structures while enabling the loading of bioactive salts and their gradual release. Sequential electro-assembly under pre-programmed salt conditions enables the manufacture of a Janus composite film with a dense and DS-containing porous layer capable of multiple functions in periodontitis treatment, which provides mechanical support, guides fibrous tissue growth, and acts as a barrier preventing its penetration into bone defects. The DS-containing porous layer delivers dual bio-signals through its morphology and the released DS, inhibiting inflammation and promoting osteogenesis. Overall, this study demonstrates the potential of electrofabrication as a customized manufacturing platform for the programmable assembly of collagen for tailored functions to adapt to specific needs in regenerative medicine.

Electro-Sorting Create Heterogeneity: Constructing A Multifunctional Janus Film with Integrated Compositional and Microstructural Gradients for Guided Bone Regeneration.

Biology remains the envy of flexible soft matter fabrication because it can satisfy multiple functional needs by organizing a small set of proteins and polysaccharides into hierarchical systems with controlled heterogeneity in composition and microstructure. Here, it is reported that controlled, mild electronic inputs (<10 V; <20 min) induce a homogeneous gelatin-chitosan mixture to undergo sorting and bottom-up self-assembly into a Janus film with compositional gradient (i.e., from chitosan-enriched layer to chitosan/gelatin-contained layer) and tunable dense-porous gradient microstructures (e.g., porosity, pore size, and ratio of dense to porous layers). This Janus film performs is shown multiple functions for guided bone regeneration: the integration of compositional and microstructural features confers flexible mechanics, asymmetric properties for interfacial wettability, molecular transport (directional growth factor release), and cellular responses (prevents fibroblast infiltration but promotes osteoblast growth and differentiation). Overall, this work demonstrates the versatility of electrofabrication for the customized manufacturing of functional gradient soft matter.

Pelvic floor muscle strength and influencing factors based on vaginal manometry among healthy women at different life stages: A multicentre cross-sectional study.

OBJECTIVE: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. DESIGN: Multicentre cross-sectional study. SETTING: Fourteen hospitals in China. POPULATION: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. METHODS: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. MAIN OUTCOME MEASURES: Maximum voluntary contraction pressure (MVCP). RESULTS: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19-51 years), premenopausal parous (aged 22-61 years), and postmenopausal (aged 40-86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. CONCLUSIONS: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life.

Advancing homogeneous networking principles for the development of fatigue-resistant, low-swelling and sprayable hydrogels for sealing wet, dynamic and concealed wounds in vivo.

Effective sealing of wet, dynamic and concealed wounds remains a formidable challenge in clinical practice. Sprayable hydrogel sealants are promising due to their ability to cover a wide area rapidly, but they face limitations in dynamic and moist environments. To address this issue, we have employed the principle of a homogeneous network to design a sprayable hydrogel sealant with enhanced fatigue resistance and reduced swelling. This network is formed by combining the spherical structure of lysozyme (LZM) with the orthotetrahedral structure of 4-arm-polyethylene glycol (4-arm-PEG). We have achieved exceptional sprayability by controlling the pH of the precursor solution. The homogeneous network, constructed through uniform cross-linking of amino groups in protein and 4-arm-PEG-NHS, provides the hydrogel with outstanding fatigue resistance, low swelling and sustained adhesion. In vitro testing demonstrated that it could endure 2000 cycles of underwater shearing, while in vivo experiments showed adhesion maintenance exceeding 24 h. Furthermore, the hydrogel excelled in sealing leaks and promoting ulcer healing in models including porcine cardiac hemorrhage, lung air leakage and rat oral ulcers, surpassing commonly used clinical materials. Therefore, our research presents an advanced biomaterial strategy with the potential to advance the clinical management of wet, dynamic and concealed wounds.

Redox-active polyphenol nanoparticles deprive endogenous glutathione of electrons for ROS generation and tumor chemodynamic therapy.

Chemodynamic therapy (CDT) based on generating reactive oxygen species (ROS) is promising for cancer treatment. However, the intrinsic H2O2 is deficient for CDT, and glutathione (GSH) eliminates ROS to protect tumor cells from ROS cytotoxicity. Herein, we propose a strategy to switch the electron flow direction of GSH for O2 reduction and ROS generation rather than ROS clearance by using P(DA-Fc) nanoparticles, which are polymerized from ferrocenecarboxylic acid (Fc) coupled dopamine. P(DA-Fc) NPs with phenol-quinone conversion ability mimic NOX enzyme to deprive electrons from GSH to reduce O2 for H2O2 generation; the following •OH release can be triggered by Fc. Semiquinone radicals in P(DA-Fc) are significantly enhanced after GSH treatment, further demonstrated with strong single-electron reduction ability by calculation. In vitro and in vivo experiments indicate that P(DA-Fc) can consume intrinsic GSH to produce endogenous ROS; ROS generation strongly depends on GSH/pH level and eventually causes tumor cell death. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to ROS producer, explores new roles of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve the efficiency of CDT. STATEMENT OF SIGNIFICANCE: P(DA-Fc) nanoparticles performing tumor microenvironment response capacity and tumor reductive power utilize ability were fabricated for CDT tumor suppression. After endocytosis by tumor cells, P(DA-Fc) deprived GSH of electrons for H2O2 and •OH release, mimicking the intrinsic ROS production conducted by NADPH, further inducing tumor cell necrosis and apoptosis. Our work makes the first attempt to reverse the function of GSH from ROS scavenger to producer, explores new functions of PDA-based nanomaterials in CDT beyond photothermal reagents and drug carriers, and provides a new strategy to improve CDT efficiency.

A suture-free, shape self-adaptive and bioactive PEG-Lysozyme implant for Corneal stroma defect repair and rapid vision restoration.

Corneal transplantation is a prevailing treatment to repair injured cornea and restore vision but faces the limitation of donor tissue shortage clinically. In addition, suturing-needed transplantation potentially causes postoperative complications. Herein, we design a PEG-Lysozyme injective hydrogel as a suture-free, shape self-adaptive, bioactive implant for corneal stroma defect repair. This implant experiences a sol-gel phase transition via an in situ amidation reaction between 4-arm-PEG-NHS and lysozyme. The physicochemical properties of PEG-Lysozyme can be tuned by the components ratio, which confers the implant mimetic corneal modulus and provides tissue adhesion to endure increased intraocular pressure. In vitro tests prove that the implant is beneficial to Human corneal epithelial cells growth and migration due to the bioactivity of lysozyme. Rabbit lamellar keratoplasty experiment demonstrates that the hydrogel can be filled into defect to form a shape-adaptive implant adhered to native stroma. The implant promotes epithelialization and stroma integrity, recovering the topology of injured cornea to normal. A newly established animal forging behavior test prove a rapid visual restoration of rabbits when use implant in a suture free manner. In general, this work provides a promising preclinical practice by applicating a self-curing, shape self-adaptive and bioactive PEG-Lysozyme implant for suture-free stroma repair.

Harnessing strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns.

Diabetic wound is a great threat to patient's health and lives. The refractory diabetic wound shows spatial inflammation patterns, in which the early-wound pattern depicts a deprived acute inflammatory response, and the long-term non-healing wound pattern delineates an excessive and persistent inflammation due to the delayed immune cell infiltration in a positive feedback loop. In this work, we give points to some strategies to normalize the dysregulated immune process based on the spatial inflammation pattern differences in diabetic wound healing. First of all, inhibiting inflammatory response to avoid subsequent persistent and excessive immune infiltration for the early diabetic wound is proposed. However, diabetic wounds are unperceptive trauma that makes patients miss the best treatment time. Therefore, we also introduce two strategies for the long-term non-healing diabetic wound. One strategy is about changing chronic wounds to acute ones, which aims to rejuvenate M1 macrophages in diabetic wounds and make spontaneous M2 polarization possible. To activate the controllable proinflammatory response, western medicine delivers proinflammatory molecules while traditional Chinese medicine develops "wound-pus promoting granulation tissue growth theory". Another strategy to solve long-term non-healing wounds is seeking switches that target M1/M2 transition directly. These investigations draw a map that delineates strategies for enhancing diabetic wound healing from the perspective of spatial inflammation patterns systematically.

Extracellular Matrix-Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing.

Macrophages play a crucial role in the complete processes of tissue repair and regeneration, and the activation of M2 polarization is an effective approach to provide a pro-regenerative immune microenvironment. Natural extracellular matrix (ECM) has the capability to modulate macrophage activities via its molecular, physical, and mechanical properties. Inspired by this, an ECM-mimetic hydrogel strategy to modulate macrophages via its dynamic structural characteristics and bioactive cell adhesion sites is proposed. The LZM-SC/SS hydrogel is in situ formed through the amidation reaction between lysozyme (LZM), 4-arm-PEG-SC, and 4-arm-PEG-SS, where LZM provides DGR tripeptide for cell adhesion, 4-arm-PEG-SS provides succinyl ester for dynamic hydrolysis, and 4-arm-PEG-SC balances the stability and dynamics of the network. In vitro and subcutaneous tests indicate the dynamic structural evolution and cell adhesion capacity promotes macrophage movement and M2 polarization synergistically. Comprehensive bioinformatic analysis further confirms the immunomodulatory ability, and reveals a significant correlation between M2 polarization and cell adhesion. A full-thickness wound model is employed to validate the induced M2 polarization, vessel development, and accelerated healing by LZM-SC/SS. This study represents a pioneering exploration of macrophage modulation by biomaterials' structures and components rather than drug or cytokines and provides new strategies to promote tissue repair and regeneration.

Electro-Biofabrication. Coupling Electrochemical and Biomolecular Methods to Create Functional Bio-Based Hydrogels.

Twenty years ago, this journal published a review entitled "Biofabrication with Chitosan" based on the observations that (i) chitosan could be electrodeposited using low voltage electrical inputs (typically less than 5 V) and (ii) the enzyme tyrosinase could be used to graft proteins (via accessible tyrosine residues) to chitosan. Here, we provide a progress report on the coupling of electronic inputs with advanced biological methods for the fabrication of biopolymer-based hydrogel films. In many cases, the initial observations of chitosan's electrodeposition have been extended and generalized: mechanisms have been established for the electrodeposition of various other biological polymers (proteins and polysaccharides), and electrodeposition has been shown to allow the precise control of the hydrogel's emergent microstructure. In addition, the use of biotechnological methods to confer function has been extended from tyrosinase conjugation to the use of protein engineering to create genetically fused assembly tags (short sequences of accessible amino acid residues) that facilitate the attachment of function-conferring proteins to electrodeposited films using alternative enzymes (e.g., transglutaminase), metal chelation, and electrochemically induced oxidative mechanisms. Over these 20 years, the contributions from numerous groups have also identified exciting opportunities. First, electrochemistry provides unique capabilities to impose chemical and electrical cues that can induce assembly while controlling the emergent microstructure. Second, it is clear that the detailed mechanisms of biopolymer self-assembly (i.e., chitosan gel formation) are far more complex than anticipated, and this provides a rich opportunity both for fundamental inquiry and for the creation of high performance and sustainable material systems. Third, the mild conditions used for electrodeposition allow cells to be co-deposited for the fabrication of living materials. Finally, the applications have been expanded from biosensing and lab-on-a-chip systems to bioelectronic and medical materials. We suggest that electro-biofabrication is poised to emerge as an enabling additive manufacturing method especially suited for life science applications and to bridge communication between our biological and technological worlds.

Deleted in lymphocytic leukemia 2 (DLEU2): a possible biomarker that holds promise for future diagnosis and treatment of cancer.

The mechanism of deleted in lymphocytic leukemia 2 (DLEU2)-long non-coding RNA in tumors has become a major point of interest in recent research related to the occurrence and development of a variety of tumors. Recent studies have shown that the long non-coding RNA DLEU2 (lncRNA-DLEU2) can cause abnormal gene or protein expression by acting on downstream targets in cancers. At present, most lncRNA-DLEU2 play the role of oncogenes in different tumors, which are mostly associated with tumor characteristics, such as proliferation, migration, invasion, and apoptosis. The data thus far show that because lncRNA-DLEU2 plays an important role in most tumors, targeting abnormal lncRNA-DLEU2 may be an effective treatment strategy for early diagnosis and improving the prognosis of patients. In this review, we integrated lncRNA-DLEU2 expression in tumors, its biological functions, molecular mechanisms, and the utility of DLEU2 as an effective diagnostic and prognostic marker of tumors. This study aimed to provide a potential direction for the diagnosis, prognosis, and treatment of tumors using lncRNA-DLEU2 as a biomarker and therapeutic target.

Isothermal exponential amplification reactions triggered by circular templates (cEXPAR) targeting miRNA.

BACKGROUND: Isothermal exponential amplification reaction (EXPAR) is an emerging amplification technique that is most frequently used to amplify microRNA (miRNA). However, EXPAR also exhibits non-specific background amplification in the absence of the targeted sequence, which limits the attainable assay sensitivity of EXPAR. METHODS AND RESULTS: A novel modified isothermal EXPAR based on circular amplification templates (cEXPAR) was developed in this study. The circular template consists of two same linear fragments that complement the target sequence, and these two linear fragments are separated by two nicking agent recognition sequences (NARS). Compared with the linear structure template, this circular template allows DNA or RNA fragments to be randomly paired with two repeated sequences and can be successfully amplified. This reaction system developed in this study could rapidly synthesize short oligonucleotide fragments (12-22 bp) through simultaneous nicking and displacement reactions. Highly sensitive chain reactions can be specifically triggered by as low as a single copy of target molecule, and non-specific amplification can be effectively eliminated in this optimized system. Moreover, the proposed approach applied to miRNA test can discriminate single-nucleotide variations between miRNAs. CONCLUSION: The newly developed cEXPAR assay provides a useful alternative tool for rapid, sensitive, and highly specific detection of miRNAs.

A Virtual Reality Platform for Context-Dependent Cognitive Research in Rodents.

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.

Advances in electrode interface materials and modification technologies for brain-computer interfaces.

Recent advances in neuroelectrode interface materials and modification technologies are reviewed. Brain-computer interface is the new method of human-computer interaction, which not only can realise the exchange of information between the human brain and external devices, but also provides a brand-new means for the diagnosis and treatment of brain-related diseases. The neural electrode interface part of brain-computer interface is an important area for electrical, optical and chemical signal transmission between brain tissue system and external electronic devices, which determines the performance of brain-computer interface. In order to solve the problems of insufficient flexibility, insufficient signal recognition ability and insufficient biocompatibility of traditional rigid electrodes, researchers have carried out extensive studies on the neuroelectrode interface in terms of materials and modification techniques. This paper introduces the biological reactions that occur in neuroelectrodes after implantation into brain tissue and the decisive role of the electrode interface for electrode function. Following this, the latest research progress on neuroelectrode materials and interface materials is reviewed from the aspects of neuroelectrode materials and modification technologies, firstly taking materials as a clue, and then focusing on the preparation process of neuroelectrode coatings and the design scheme of functionalised structures.

Single Step Assembly of Janus Porous Biomaterial by Sub-Ambient Temperature Electrodeposition.

Janus porous biomaterials are gaining increasing attention and there are considerable efforts to develop simple, rapid, and scalable methods capable of tuning micro- and macro-structures. Here, a single-step electro-fabrication method to create a Janus porous film by the electrodeposition of the amino-polysaccharide chitosan is reported. Specifically, a Janus structure emerges spontaneously when electrodeposition is performed at sub-ambient temperature (0-5 °C). Sub-ambient temperature electrodeposition experiments show that: a Janus microstructure emerges (potentially as the result of a subtle alteration of the intermolecular interactions responsible for self-assembly); important microstructural features (pore size, porosity, and thicknesses) can be tuned by conditions; and this method is readily scalable (vs serial printing) and can yield complex tubular structures with Janus faces. In vitro studies demonstrate anisotropic cell guidance, and in vivo studies using a rat calvarial defect model further confirm the beneficial features of such Janus porous film for guided bone regeneration. In summary, these results further demonstrate that electro-fabrication provides a simple and scalable platform technology for the controlled functional structures of soft matter for applications in regenerative medicine.

1D@2D Hierarchical Structures of Co(OH)x Nanosheets on NiMoOx Nanorods Can Mediate Alkaline Hydrogen Evolution with Industry-Level Current Density and Stability.

Developing efficient electrocatalysts at ampere-scale current densities is of paramount importance to advance industrial applications of alkaline water electrolysis. Herein, a hierarchical nanostructured electrocatalyst with two-dimensional Co(OH)x nanosheets grown on one-dimensional NiMoOx nanorods over three-dimensional porous Ni foam substrate is designed. The resulting catalyst delivers ultrahigh hydrogen evolution reaction (HER) activity in the alkaline solution, which only requires overpotentials of 185 and 332 mV to achieve the current densities of -500 and -1000 mA cm-2 in 1.0 m KOH, respectively, and shows robust stability at -1000 mA cm-2 for 11 days. The unique 1D @ 2D hierarchical structures with abundant hetero-interfaces can not only expose sufficient active sites but also boost alkaline HER kinetics with fast water dissociation ability. This present work may pave a new insight to design efficient electrocatalysts with hierarchical structures for alkaline HER with industry-level current density and stability.

Electrical Signal Initiates Kinetic Assembly of Collagen to Construct Optically Transparent and Geometry Customized Artificial Cornea Substitutes.

Corneal transplantation is an effective treatment for reconstructing injured corneas but is very limited due to insufficient donors, which has led to a growing demand for development of artificial corneal substitutes (ACSs). Collagen is a potential building block for ACS fabrication, whereas technically there are limited capabilities to control the collagen assembly for creating highly transparent collagen ACSs. Here, we report an electro-assembly technique to kinetically control collagen assembly on the nanoscale that allows the yielding collagen ACSs with structure determined superior optics. Structurally, the kinetically electro-assembled collagen (KEA-Col) is composed of partially aligned microfibrils (∼10 nm in diameter) with compacted lamellar organization. Optical analysis reveals that such microstructure is directly responsible for its optimal light transmittance by reducing light scattering. Moreover, this method allows the creation of complex three-dimensional geometries and thus is convenient to customize collagen ACSs with specific curvatures to meet refractive power requirements. Available properties (e.g., optics and mechanics) of cross-linked KEA-Cols were studied to meet the clinical requirement as ACSs, and in vitro tests further proved their beneficial characteristics of cell growth and migration. An in vivo study established a rabbit lamellar keratectomy corneal wound model and demonstrated the customized collagen ACSs can adapt to the defective cornea and support epithelial healing as well as stroma integration and reconstruction with lower immunoreaction compared with commercial xenografts, which suggests its promising application prospects. More broadly, this work illustrates the potential for enlisting electrical signals to mediate collagen's assembly and microstructure organization for specific structural functionalization for regenerative medicine.

Electro-assembly of a dynamically adaptive molten fibril state for collagen.

Collagen is a biological building block that is hierarchically assembled into diverse morphological structures that, in some cases, is dynamically adaptive in response to external cues and in other cases forms static terminal structures. Technically, there is limited capabilities to guide the emergence of collagen's hierarchical organization to recapitulate the richness of biological structure and function. Here, we report an electro-assembly pathway to create a dynamically adaptive intermediate molten fibril state for collagen. Structurally, this intermediate state is composed of partially aligned and reversibly associating fibrils with limited hierarchical structure. These molten fibrils can be reversibly reconfigured to offer dynamic properties such as stimuli-stiffening, stimuli-contracting, self-healing, and self-shaping. Also, molten fibrils can be guided to further assemble to recapitulate the characteristic hierarchical structural features of native collagen (e.g., aligned fibers with D-banding). We envision that the electro-assembly of collagen fibrils will provide previously unidentified opportunities for tailored collagen-based biomedical materials.

Lysozyme Amyloid Fibril-Integrated PEG Injectable Hydrogel Adhesive with Improved Antiswelling and Antibacterial Capabilities.

Hydrogels with inherent antibacterial activities have been attracting increasing attention, particularly for biomedical applications. Biology provides a range of materials and mechanisms to meet diverse requirements for bacterial combating. Lysozyme after fibrillation (LZMF) has a much superior antibacterial ability than globular native lysozyme due to its decreased positive charges and increased hydrophobic ß-sheet component. Here, we propose to design a poly(ethylene glycol) (PEG) cross-linked LZMF composite antibacterial hydrogel by utilizing the nucleophilic substitution reaction between LZMF and N-hydroxysuccinimide end groups on four-arm PEG-NHS. The generated PEG-LZMF hydrogel is bacteria-resistant both in vitro and in vivo as expected and has good biocompatibility. Moreover, the volume expansion of PEG can be significantly inhibited due to the presence of hydrophobic lysozyme amyloid fibrils. In addition, the relatively fast cross-linking reaction can make PEG-LZMF both injectable and shape-compatible. The simultaneous reaction with tissue-exposed -NH2 or -SH also confers a tissue-adhesive ability. We envision that this hydrophobic lysozyme amyloid fibril-integrated PEG composite hydrogel can effectively adhere/protect open wounds and internal incisions and suppress pathogen infection through a biomimetic antibacterial mechanism. Considering the simple fabrication process, this multifunctional PEG-LZMF antibacterial hydrogel is promising for clinical transformation.