Multiple Stimuli-Responsive Color-Changing Polymer Materials for Reversible Writing and Anti-Counterfeiting.

Polymer materials with multiple stimuli-responsive properties have demonstrated many potential and practical applications. By covalently introducing spiropyran (SP1) and spirothiopyran (STP) into the polyurethane backbone, photochromic, mechanochromic, and thermally discolored polymer materials have been prepared. In this work, we report for the first time that white light (violet, blue, and green light) above a certain intensity can activate STP to green color. Based on the above discovery, the polyurethane with SP1 and STP can exhibit reversible three-color changes (brown, green, and purple) in response to four stimuli: ultraviolet irradiation, white light irradiation, mechanical stress, and heat. The color-changing polymer materials have high color contrast and excellent reversibility, and can be used for reversible writing, anticounterfeiting and information encryption, etc.

Nanocomposite hyaluronic acid adhesive hydrogel with controllable drug release for bone regeneration.

Hyaluronic acid (HA) hydrogels have arisen as candidate materials to simulate the extracellular matrix and restore the functions of both cartilage and hard bones. However, integration of bone tissue adhesion and long-term osteogenic properties in one hydrogel is often ignored. Herein, a strategy to construct nanocomposite hydrogel with host tissue adhesive properties, enhanced mechanical strength, improved stability and osteogenic effects was developed. Simvastatin (SIM) was firstly incorporated into zeolitic imidazolate framework-8 (ZIF-8) and surface decoration with hydroxyapatite was realized to obtain SIM loaded and hydroxyapatite modified ZIF-8 particles (SP). As the inorganic strengthening component, SP could further cross-link the mixture of dopamine-hyaluronic acid (dHA) and tannic (TA) via coordination interaction to fabricate the hybrid adhesive hydrogel (dHA/TA/SP). Sufficient phenolic groups endowed dHA/TA/SP with excellent tissue adhesion and antibacterial properties, while incorporation of SP significantly improved the mechanical strength and stability of hydrogel. Further, due to the multiple protective effects of ZIF-8 and hydrogel, SIM was sustainably released from dHA/TA/SP. Together with the active Zn2+ and Ca2+, the expressions of ALP, OCN and RUNX2 were upregulated, and the mineralization was also promoted. With significant osteogenic effect in vitro and in vivo, this nanocomposite adhesive hydrogel holds great potential for bone defects repair.

Bionic double-crosslinked hydrogel of poly (γ-glutamic acid)/poly (N-(2-hydroxyethyl) acrylamide) with ultrafast gelling process and ultrahigh burst pressure for emergency rescue.

Injectable adhesive hydrogels combining rapid gelling with robust adhesion to wet tissues are highly required for fast hemostasis in surgical and major trauma scenarios. Inspired by the cross-linking mechanism of mussel adhesion proteins, we developed a bionic double-crosslinked (BDC) hydrogel of poly (γ-glutamic acid) (PGA)/poly (N-(2-hydroxyethyl) acrylamide) (PHEA) fabricated through a combination of photo-initiated radical polymerization and hydrogen bonding cross-linking. The BDC hydrogel exhibited an ultrafast gelling process within 1 s. Its maximum adhesion strength to wet porcine skin reached 254.5 kPa (9 times higher than that of cyanoacrylate (CA) glue) and could withstand an ultrahigh burst pressure of 626.4 mmHg (24 times higher than that of CA glue). Notably, the BDC hydrogel could stop bleeding within 10 s from a rat liver incision 10 mm long and 5 mm deep. The wound treated with the BDC hydrogel healed faster than the control groups, underlining the potential for emergency rescue and wound care scenarios.

Biological applications of lipoic acid-based polymers: an old material with new promise.

Lipoic acid (LA) is a versatile antioxidant that has been used in the treatment of various oxidation-reduction diseases over the past 70 years. Owing to its large five-membered ring tension, the dynamic disulfide bond of LA is highly active, enabling the formation of poly(lipoic acid) (PLA) via ring-opening polymerization (ROP). Herein, we first summarize disulfide-mediated ROP polymerization strategies, providing basic routes for designing and preparing PLA-based materials. PLA, as a biologically derived, low toxic, and easily modified material, possesses dynamic disulfide bonds and universal non-covalent carboxyl groups. We also shed light on the biomedical applications of PLA-based materials based on their biological and structural features and further divide recent works into six categories: antibacterial, anti-inflammation, anticancer, adhesive, flexible electronics, and 3D-printed tissue scaffolds. Finally, the challenges and future prospects associated with the biomedical applications of PLA are discussed.

Degradable Nanohydroxyapatite-Reinforced Superglue for Rapid Bone Fixation and Promoted Osteogenesis.

Bone glue with robust adhesion is crucial for treating complicated bone fractures, but it remains a formidable challenge to develop a "true" bone glue with high adhesion strength, degradability, bioactivity, and satisfactory operation time in clinical scenarios. Herein, inspired by the hydroxyapatite and collagen matrix composition of natural bone, we constructed a nanohydroxyapatite (nHAP) reinforced osteogenic backbone-degradable superglue (O-BDSG) by in situ radical ring-opening polymerization. nHAP significantly enhances adhesive cohesion by synergistically acting as noncovalent connectors between polymer chains and increasing the molecular weight of the polymer matrix. Moreover, nHAP endows the glue with bioactivity to promote osteogenesis. The as-prepared glue presented a 9.79 MPa flexural adhesion strength for bone, 4.7 times that without nHAP, and significantly surpassed commercial cyanoacrylate (0.64 MPa). O-BDSG exhibited degradability with 51% mass loss after 6 months of implantation. In vivo critical defect and tibia fracture models demonstrated the promoted osteogenesis of the O-BDSG, with a regenerated bone volume of 75% and mechanical function restoration to 94% of the native tibia after 8 weeks. The glue can be flexibly adapted to clinical scenarios with a curing time window of about 3 min. This work shows promising prospects for clinical application in orthopedic surgery and may inspire the design and development of bone adhesives.

A metal-organic framework-integrated composite for piezocatalysis-assisted tumour therapy: design, related mechanisms, and recent advances.

With the growing need for more effective tumour treatment, piezocatalytic therapy has emerged as a promising approach due to its distinctive capacities to generate ROS through stress induction and regulate the hypoxic state of the TME. MOF-based piezocatalysts not only possess the benefits of piezocatalysis but also exhibit several advantages associated with MOFs, such as tunable pore size, large specific surface area, and good biocompatibility. Therefore, they are expected to become a powerful promoter of piezocatalytic therapy. This review elaborates on the fundamental principles of piezocatalysis and summarises recent advances in the piezocatalytic therapy and combination therapies of tumours, generalising the strategies for constructing piezocatalytic systems based on MOFs. Finally, the challenges confronted and future opportunities for the design and application of piezocatalytic MOF anticancer systems have been discussed.

Heparin-network-mediated long-lasting coatings on intravascular catheters for adaptive antithrombosis and antibacterial infection.

Bacteria-associated infections and thrombosis, particularly catheter-related bloodstream infections and catheter-related thrombosis, are life-threatening complications. Herein, we utilize a concise assembly of heparin sodium with organosilicon quaternary ammonium surfactant to fabricate a multifunctional coating complex. In contrast to conventional one-time coatings, the complex attaches to medical devices with arbitrary shapes and compositions through a facile dipping process and further forms robust coatings to treat catheter-related bloodstream infections and thrombosis simultaneously. Through their robustness and adaptively dissociation, coatings not only exhibit good stability under extreme conditions but also significantly reduce thrombus adhesion by 60%, and shows broad-spectrum antibacterial activity ( > 97%) in vitro and in vivo. Furthermore, an ex vivo rabbit model verifies that the coated catheter has the potential to prevent catheter-related bacteremia during implantation. This substrate-independent and portable long-lasting multifunctional coating can be employed to meet the increasing clinical demands for combating catheter-related bloodstream infections and thrombosis.

Metal-organic framework-based platforms for implantation applications: recent advances and challenges.

The development of minimally invasive technology has promoted the widespread use of implant interventional materials, which play an important role in alleviating patients' pain during and after surgery. Metal-organic frameworks (MOFs) and their related hybrids formed by bridging ligands and metal nodes via covalent bonds represent one of the smart platforms in implant interventional fields due to their large surface area, adjustable compositions and structures, biodegradability, etc. Significant progresses in the implantation application of MOF-based materials have been achieved recently, but these studies are still in the initial stage. This review highlights the recent advances of MOFs and their related hybrids in orthopedic implantation, cardio-vascular implantation, neural tissue engineering, and biochemical sensing. Each correction between the structural features of MOFs and their corresponding implanted works is highlighted. Finally, the confronting challenges and future perspectives in the implant interventional field are discussed.

Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections.

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Biomimetic, self-coacervating adhesive with tough underwater adhesion for ultrafast hemostasis and infected wound healing.

Massive bleeding and wound infection due to severe traumas pose a huge threat to the life and health of sufferers; therefore, it is of clinical importance to fabricate adhesives with rapid hemostatic and superior antibacterial capabilities. However, the weak wet adhesion and insufficient function of existing bioadhesives limits their practical application. In this study, a sandcastle worm protein inspired polyelectrolyte self-coacervate adhesive of poly-γ-glutamic acid (PGA) and lysozyme (LZM) was developed. The adhesive exhibited strong underwater adhesion to various surfaces (>250 kPa for solid plates and >50 kPa for soft tissues) and maintained a 80 kPa even when soaked in water for 7 days. Rat liver and tail defect bleeding models revealed that the hemostatic efficiency was superior to that of commercial samples. The in vitro antimicrobial tests showed that the bacterial inhibition to Staphylococcus aureus and Escherichia coli reached almost 100%. Additionally, the infected wound regeneration model demonstrated that the healing rate of the adhesive group was about 100% within 15 days, which was greater than that of the control group. In vitro and in vivo experiments proved that this facilely prepared adhesive will be a promising material to fulfil the integration functions for rapid wound closure and facilitating wound healing.

Tunable backbone-degradable robust tissue adhesives via in situ radical ring-opening polymerization.

Adhesives with both robust adhesion and tunable degradability are clinically and ecologically vital, but their fabrication remains a formidable challenge. Here we propose an in situ radical ring-opening polymerization (rROP) strategy to design a backbone-degradable robust adhesive (BDRA) in physiological environment. The hydrophobic cyclic ketene acetal and hydrophilic acrylate monomer mixture of the BDRA precursor allows it to effectively wet and penetrate substrates, subsequently forming a deep covalently interpenetrating network with a degradable backbone via redox-initiated in situ rROP. The resulting BDRAs show good adhesion strength on diverse materials and tissues (e.g., wet bone >16 MPa, and porcine skin >150 kPa), higher than that of commercial cyanoacrylate superglue (~4 MPa and 56 kPa). Moreover, the BDRAs have enhanced tunable degradability, mechanical modulus (100 kPa-10 GPa) and setting time (seconds-hours), and have good biocompatibility in vitro and in vivo. This family of BDRAs expands the scope of medical adhesive applications and offers an easy and environmentally friendly approach for engineering.

Aquatic Diatoms-Inspired Universal Adhesive Coacervates Triggered by Water.

Adhesives with strong underwater adhesion performance are urgently needed in diverse areas. However, designing adhesives with long-term stability to diverse materials underwater in a facile way is challenging. Here, inspired by aquatic diatoms, a series of novel biomimetic universal adhesives is reported that shows tunable performance with robust and long-lasting stable underwater adhesion to various substrates, including wet biological tissues. The versatile and robust wet-contact adhesives are pre-polymerized by N-[tris(hydroxymethyl)methyl]acrylamide, n-butyl acrylate, and methylacrylic acid in dimethyl sulfoxide and spontaneously coacervated in water triggered by solvent exchange. The synergistic interaction between hydrogen bonding and hydrophobic interaction allows the hydrogels with instant and strong adhesion to various substrate surfaces. The slowly formed covalent bonds enhance cohesion and adhesion strength in hours. The spatial and timescale-dependent adhesion mechanism endows the adhesives with strong and long-lasting stable underwater adhesion to be coupled with fault-tolerant convenient surgical operations.

Water-Triggered Segment Orientation of Long-Lasting Anti-Biofouling Polyurethane Coatings on Biomedical Catheters via Solvent Exchange Strategy.

The formation of biofilm and thrombus on medical catheters poses a significant life-threatening concern. Hydrophilic anti-biofouling coatings upon catheter surfaces with complex shapes and narrow lumens are demonstrated to have the potential in reducing complications. However, their effectiveness is constrained by poor mechanical stability and weak substrate adhesion. Herein, a novel zwitterionic polyurethane (SUPU) with strong mechanical stability and long-term anti-biofouling is developed by controlling the ratio of sulfobetaine-diol and ureido-pyrimidinone. Once immersed in water, as-synthesized zwitterionic coating (SUPU3 SE) would undergo a water-driven segment reorientation to obtain much higher durability than its direct drying one, even under various extreme treatments, including acidic solution, abrasion, ultrasonication, flushing, and shearing, in PBS at 37 °C for 14 days. Moreover, SUPU3 SE coating could achieve a 97.1% of exceptional reducing protein fouling, complete prevention of cell adhesion, and long-lasting anti-biofilm performance even after 30 days. Finally, the good anti-thrombogenic formations of SUPU3 SE coating with bacterial treatment are validated in blood circulation through an ex vivo rabbit arteriovenous shunt model. This work provides a facile approach to fabricating stable hydrophilic coating through a simple solvent exchange to reduce thrombosis and infection of biomedical catheters.

Brush Polymer Coatings with Hydrophilic Main-Chains for Improving Surface Antibacterial Properties.

Polymer coatings with improved surface antibacterial properties are of great importance for the application and development of implantable medical devices. Herein, we report the design, preparation, and antibacterial properties of a series of brush polymers (Dex-KEs) with hydrophilic dextran main-chains and mixed-charge polypeptide (KE) side-chains. Dex-KEs showed higher bactericidal activity and antifouling and antibiofilm properties than maleic acid modified dextran (Dex-Ma), KE, Dex-Ma/KE blend coatings, and brush polymer coatings with hydrophobic main-chains (AcDex-KEs). They also showed negligible in vitro cytotoxicity toward different mammalian cells and good in vivo biocompatibility. Dex-KE-coated implants exhibited potent in vivo resistance to bacterial infection before or after implantation.

Salt-Triggered Adaptive Dissociation Coating with Dual Effect of Antibacteria and Anti-Multiple Encrustations in Urological Devices.

Bacterial infections and multiple encrustations are life-threatening complications in patients implanted with urological devices. Limited by time-consuming procedures and substrate dependence, it is difficult to simultaneously prevent the aforementioned complications. Herein, is reported the design of a salt-triggered chondroitin sulfate complex (CS/Si-N+ ) coating with adaptive dissociation, which realizes the dual functions of antibacterial and anti-multiple encrustations in urological devices with arbitrary shapes. The existence of covalent interactions between the complex and the interface ensures the formation of a robust coating, especially in harsh environments. Benefiting from the adaptive dissociation of the ion pairs in the CS/Si-N+ coating in urine electrolytes, the exposed ion groups and enhanced hydrophilicity are more conducive to the inhibition of bacterial infection and multiple encrustations simultaneously. The coating exhibits broad-spectrum bactericidal effects. As a proof of concept, in a simulated metabolic encrustation model, the coating exhibits significant advantages in resisting calcium oxalate encrustation, with a reduction in the calcium content by over 90%. In addition, this non-leachable all-in-one coating shows good biocompatibility in a pig in vivo model. Such a coating strategy is expected to be a practical approach for preventing urological medical device-related complications.

Optimization of Alkyl Side Chain Length in Polyimide for Gate Dielectrics to Achieve High Mobility and Outstanding Operational Stability in Organic Transistors.

Alkyl chain modification strategies in both organic semiconductors and inorganic dielectrics play a crucial role in improving the performance of organic thin-film transistors (OTFTs). Polyimide (PI) and its derivatives have received extensive attention as dielectrics for application in OTFTs because of flexibility, high-temperature resistance, and low cost. However, low-temperature solution processing PI-based gate dielectric for flexible OTFTs with high mobility, low operating voltage, and high operational stability remains an enormous challenge. Furthermore, even though di-n-decyldinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (C10-DNTT) is known to have very high mobility as an air-stable and high-performance organic semiconductor, the C10-DNTT-based TFTs on the PI gate dielectrics still showed relatively low mobility. Here, inspired by alkyl side chain engineering, we design and synthesize a series of PI materials with different alkyl side chain lengths and systematically investigate the PI surface properties and the evolution of organic semiconductor morphology deposited on PI surfaces during the variation of alkyl side chain lengths. It is found that the alkyl side chain length has a critical influence on the PI surface properties, as well as the grain size and molecular orientation of semiconductors. Good field-effect characteristics are obtained with high mobilities (up to 1.05 and 5.22 cm2/Vs, which are some of the best values reported to date), relatively low operating voltage, hysteresis-free behavior, and high operational stability in OTFTs. These results suggest that the strategy of optimizing alkyl side-chain lengths opens up a new research avenue for tuning semiconductor growth to enable high mobility and outstanding operational stability of PI-based OTFTs.

Regulable Polyelectrolyte-Surfactant Complex for Antibacterial Biomedical Catheter Coating via a Readily Scalable Route.

Constructing multifunctional surfaces is one of the practical approaches to address catheter-related multiple complications but is generally time-consuming and substrate-dependent. Herein, a novel anti-adhesion, antibacterial, low friction, and robustness coating on medical catheters are developed via a universal and readily scalable method based on a regulable polyelectrolyte surfactant complex. The complex is rapidly assembled in one step by electrostatic and hydrophobic interactions between organosilicon quaternary ammonium surfactant (N+ Si ) and adjustable polyelectrolyte with cross-linkable, anti-adhesive, and anionic groups. The alcohol-soluble feature of the complex is conducive to the rapid formation of coatings on any medical device with arbitrary shapes via dip coating. Different from the conventional polyelectrolyte-surfactant complex coating, the regulated complex coating with nonleaching mode could be stable in harsh conditions (high concentration salt solution, organic reagents, etc.) because of the cross-linked structure while improving the biocompatibility and reducing the adhesion of various bacteria, proteins, and blood cells. The coated catheter exhibits good antibacterial infection in vitro and in vivo, owing to the synergistic effect of N+ Si and zwitterionic groups. Therefore, the rationally designed complex supplies a facile coating approach for the potential development in combating multiple complications of the medical catheter.

Functional gelatin hydrogel scaffold with degraded-release of glutamine to enhance cellular energy metabolism for cartilage repair.

Cartilage defect is one of the most common pathogenesis of osteoarthritis (OA), a degenerative joint disease that affects millions of people globally. Due to lack of nutrition and local metabolic inertia, the repair of cartilage has always been a difficult problem to be urgently solved. Herein, a functional gelatin hydrogel scaffold (GelMA-AG) chemically modified with alanyl-glutamine (AG) is proposed and prepared. The GelMA-AG can release glutamine through in vivo degradation that can activate the energy metabolism process of chondrocytes, thus effectively promoting damaged cartilage repair. The results demonstrate that compared with the AG-free gelatin hydrogel (GelMA), GelMA-AG exhibits an increase in both the mitochondrial membrane potential level and the production of intracellular adenosine triphosphate (ATP), while the intracellular reactive oxygen species (ROS) of chondrocytes is decreased, thus contributing to the higher level of cellular metabolism and the lower inflammation in cartilage tissue. In contrast to GelMA (Reduced Modulus (Er): 24.33 MPa), the Er value of the remodeled rabbit knee articular cartilage is up to 70.14 MPa, which is more comparable to natural cartilage. In particular, this strategy does not involve exogenous cells and growth factors, and the therapeutic strategy of actively regulating the metabolic microenvironment through a functional gelatin hydrogel scaffold represents a new and prospective idea for the design of tissue engineering biomaterials in cartilage repair with simplification and effectiveness.

Mussel-inspired polysaccharide-based sponges for hemostasis and bacteria infected wound healing.

Effective bleeding control and wound protecting from infection play critical roles in the tissue healing process. However, local hemostats are not involved in the whole healing processes to promote the final healing efficiency. Here, a multi-functional mussel-inspired polysaccharide-based sponge with hemostatic, antibacterial and adhesive properties was fabricated via cryopolymerization of oxidized dextran (OD), carboxymethyl chitosan (CC) and polydopamine nanoparticles (PDA-NPs), followed by lyophilization. Combining with the adsorbed thrombin, the sponges yielded a considerably lower amount of blood than the commercially available hemostatic dressings. Benefiting from the high photo-thermal transition efficiency of PDA-NPs, the sponges exhibited excellent antibacterial activity to both gram positive and negative bacteria. Owing to the rapid hemostatic activity and effective infection resistance, the sponges illustrated the significantly acceleratory wound healing efficiency compared with the control group. The thrombin-loaded OD/CC-PDA polysaccharide-based sponge has great potential for future clinical use as wound dressing.

Charge-switchable MOF nanocomplex for enhanced biofilm penetration and eradication.

Bacterial biofilm is notorious for causing chronic infections, whose antibiotic treatment is bringing about severe multidrug resistance and environmental contamination. Stimuli-responsive nanocarriers have become encouraging materials to combat biofilm infections with high efficiency and low side effect. Herein, a charge-switchable and pH-responsive nanocomplex is fabricated via a facile aqueous one-pot zeolitic imidazolate framework-8 (ZIF-8) encapsulation of proteinase K (PK) and photosensitizer Rose Bengal (RB), for enzymatic and photodynamic therapies (PDT) against biofilm infections. Once encountering in acidic microenvironment, the surface charge of nanocomplex can switch self-adaptively from negative to positive, hence remarkably facilitating the biofilm penetration of nanocomplex. After acid-induced decomposition of nanocomplex, the released PK degrades biofilm matrix and loosens its structure, promoting diffusion of RB inside the biofilm. Afterwards, upon visible light illumination, the RB generates highly reactive oxygen species (ROS), which can readily and efficiently kill the remained bacteria even in the biofilm core. The charge-assisted penetration makes PK and RB fully functional, resulting in a cooperative effect concerning high biofilm eradication capacity, as testified by biofilm models both in vitro and in vivo. The green synthesis and good therapeutic performance of the nanocomplex manifests its considerable potential as a nontoxic and effective platform for biofilm treatment.