Hybrid Transition-Metal Oxide and Nitride@N-Doped Reduced Graphene Oxide Electrodes for High-Performance, Flexible, and All-Solid-State Supercapacitors.

Nanoscale composites for high-performance electrodes employed in flexible, all-solid-state supercapacitors are being developed. A series of binder-free composites, each consisting of a transition bimetal oxide, a metal oxide, and a metal nitride grown on N-doped reduced graphene oxide (rGO)-wrapped nickel foam are obtained by using a universal strategy. Three different transition metals, Co, Mo, and Fe, are separately compounded with nickel ions, which originate from the nickel foam, to form three composites, NiCoO2 @Co3 O4 @Co2 N, NiMoO4 @MoO3 @Mo2 N, and NiFe2 O4 @Fe3 O4 @Fe2 N, respectively. These as-prepared active materials have similar regular variation patterns in their properties, including better conductivity and battery-mimicking pseudocapacitance, which result in their high whole-electrode capacitance performance [2598.3 F g-1 (39.85 F cm-2 ), 3472.6 F g-1 (41.43 F cm-2 ) and 1907.5 F g-1 (3.41 F cm-2 ) for the composites incorporating Co, Mo, and Fe, respectively]. The as-assembled flexible, all-solid-state NiCoO2 @Co3 O4 @Co2 N//KOH/PVA//NiCoO2 @Co3 O4 @Co2 N device can be easily bent and exhibits high energy density and power density of 92.8 Wh kg-1 and 1670.4 W kg-1 , respectively. The universality of this design strategy could allow it to be employed in producing hybrid materials for high-performance energy-storage devices.

An Anisotropic Hydrogel Based on Mussel-Inspired Conductive Ferrofluid Composed of Electromagnetic Nanohybrids.

Anisotropic hydrogels with a hierarchical structure can mimic biological tissues, such as neurons or muscles that show directional functions, which are important factors for signal transduction and cell guidance. Here, we report a mussel-inspired approach to fabricate an anisotropic hydrogel based on a conductive ferrofluid. First, polydopamine (PDA) was used to mediate the formation of PDA-chelated carbon nanotube-Fe3O4 (PFeCNT) nanohybrids and also used as a dispersion medium to stabilize the nanohybrids to form a conductive ferrofluid. The ferrofluid can respond to an orientated magnetic field and be programed to form aligned structures, which were then frozen in a hydrogel network formed via in situ free-radical polymerization and gelation. The resulted hydrogel shows directional conductive and mechanical properties, mimicking an oriented biological tissue. Under external electrical stimulation, the orientated PFeCNT nanohybrids can be sensed by the myoblasts cultured on the hydrogel, resulting in the oriented growth of cells. In summary, the mussel-inspired anisotropic hydrogel with its aligned structural complexity and anisotropic properties together with the cell affinity and tissue adhesiveness is a potent multifunctional biomaterial for mimicking oriented tissues to guide cell proliferation and tissue regeneration.

A Mussel-Inspired Conductive, Self-Adhesive, and Self-Healable Tough Hydrogel as Cell Stimulators and Implantable Bioelectronics.

A graphene oxide conductive hydrogel is reported that simultaneously possesses high toughness, self-healability, and self-adhesiveness. Inspired by the adhesion behaviors of mussels, our conductive hydrogel shows self-adhesiveness on various surfaces and soft tissues. The hydrogel can be used as self-adhesive bioelectronics, such as electrical stimulators to regulate cell activity and implantable electrodes for recording in vivo signals.

Polydopamine-armored zeolitic imidazolate framework-8-incorporated zwitterionic hydrogel with multifunctional properties for infected wound healing.

Diabetic skin wound healing is compromised by bacterial infections, oxidative stress, and vascular disruption, leading to delayed recovery and potential complications. This study developed an antibacterial, antioxidant, and adhesive hydrogel dressing that promotes rapid bacterial-infected diabetic wound healing using the biological macromolecule of polydopamine (PDA). This hydrogel comprised PDA-armored zeolitic imidazolate framework-8 nanoparticles (PDA@ZIF-8 NPs) combined with a second armor of zwitterionic polymer network (poly(acrylamide-co-sulfobetaine methacrylate); PAS), realizing low concentration Zn2+ release, good adhesion (14.7 kPa for porcine skin), and improved tensile strength (83.2 kPa). The hydrogel exhibited good antibacterial efficacy against both Staphylococcus aureus (S. aureus, 92.8 %), Escherichia coli (E. coli, 99.6 %) and methicillin-resistant S. aureus (MRSA, 99.2 %), which was attributed to the properties of the incorporated PDA@ZIF-8 NPs. Notably, in vitro, the PDA@ZIF-8 PAS hydrogel not only promoted fibroblast proliferation and migration but also facilitated endothelial cell angiogenesis. In vivo, the PDA@ZIF-8 PAS hydrogel retained its Zn2+-releasing function and effectively suppressed bacterial growth in infected wounds, thereby accelerating the regeneration of both normal and diabetic wounds. This multiarmored hydrogel is a promising sustained-release carrier for functional metal ions and drugs, making it applicable for not only skin healing, but potentially the regeneration of other complex tissues.

Long-term antibacterial, antioxidative, and bioadhesive hydrogel wound dressing for infected wound healing applications.

Bacterial infection and oxidative stress hinder clinical wound healing. Therefore, wound dressings with antibacterial and antioxidative properties are urgently needed. In this study, a type of quaternized lignin (QL) functionalized poly(hexamethylene biguanide) hydrochloride (PHMB) complex incorporated polyacrylamide (QL-PHMB-PAM) hydrogel was developed as a multifunctional dressing material for the promotion of infected wound repair. Owing to the abundant catechol groups of quaternized lignin, the QL-PHMB-PAM hydrogel exhibited robust repeatable adhesiveness to various substrates with antioxidative properties. Additionally, the antibacterial components of PHMB in the QL-PHMB-PAM composite hydrogel showed high efficiency and long-term antibacterial activity against Staphylococcus aureus (S.aureus), Escherichia coli (E.coli), and methicillin-resistant S. aureus (MRSA; up to 100%). Furthermore, in vivo experiments indicated that this multifunctional hydrogel accelerated the healing of S. aureus-infected wounds by promoting the reconstruction of blood vessels and hair follicles. These results demonstrate that this antioxidative, antibacterial, and bioadhesive hydrogel is a promising alternative wound dressing material for the prevention of bacterial infections and the acceleration of infected wound regeneration.

Bioadhesive and electroactive hydrogels for flexible bioelectronics and supercapacitors enabled by a redox-active core-shell PEDOT@PZIF-71 system.

Stretchable and conductive hydrogels are rapidly emerging as new generation candidates for wearable devices. However, the poor electroactivity and bioadhesiveness of traditional conductive hydrogels has limited their applications. Herein, a mussel-inspired strategy is proposed to prepare a specific core-shell redox-active system, consisting of a polydopamine (PDA) modified zeolitic imidazolate framework 71 (ZIF-71) core, and a poly 3,4-ethylenedioxythiopene (PEDOT) shell. Owing to the abundant catechol groups, PEDOT can be assembled on the surface of ZIF-71 to create a redox-active system. The core-shell nanoparticles could act as a redox-active nanofiller to develop a conductive polyacrylamide (PAM) hydrogel with energy-storage properties. The core-shell PEDOT@PZIF-71 system provides a mussel-inspired environment in the hydrogel matrix and endows the hydrogel with stretchability and adhesiveness. The hydrogel can be applied as a functional electrode for both bioelectronics and supercapacitors. Moreover, this hydrogel exhibits favorable biocompatibility and can be implanted in vivo for biosignal measurement without causing inflammation. This redox-active core-shell PEDOT@PZIF-71 system provides a promising strategy for the design of hydrogel-based wearable electronic devices.

Tertiary amines convert 1O2 to H2O2 with enhanced photodynamic antibacterial efficiency.

Photodynamic inactivation (PDI) is a promising approach to combat the increasing global multi-drug resistance crisis. However, the very short half-life of 1O2 and the inevitable photobleaching of photosensitizer (PS) are the inherent drawbacks that largely compromise its therapeutic efficiency. Here, we report a ROS conversion strategy that simultaneously addresses these issues. Based on a photodynamic model system where riboflavin (RF) served as the PS, we have clearly shown that about 93.2% of 1O2 could be converted to hydrogen peroxide (H2O2) in the presence of tertiary amine. The less reactivity of H2O2 (v.s.1O2) could retard the photobleaching of riboflavin by 88.9%. Orders of magnitude extended half-life of ROS (H2O2v.s.1O2) and retarded photobleaching of RF synergistically provide a more persistent oxidization that increased the oxidation capacity of the photodynamic model system by 56.6%. Consequently, it is able to improve the therapeutic efficiencies from 89.6% to 99.1% in combating methicillinresistant S. aureus (MRSA) and from 64.0% to 92.0% in eradicating S. aureus biofilm on biomaterials within a 5-min simulated sunlight illumination. The reinforced photodynamic model system could also significantly accelerate the healing & maturing of MRSA infected skin wound as compared to that of clinically used vancomycin. The generality of "ROS conversion" among different amines and different photosensitizers have been verified. These findings may inspire many creative approaches to increase the antibacterial efficiency of current photodynamic treatments for diverse applications.

Zwitterionic/active ester block polymers as multifunctional coatings for polyurethane-based substrates.

Bacterial-associated infection, blood coagulation, and tissue adhesion are severe issues associated with biomedical implants and devices in clinic applications. Here, we report a general strategy to simultaneously tackle these issues on polyurethane (PU)-based substrates. Taking advantage of reversible addition-fragmentation chain transfer (RAFT) polymerization, well-defined zwitterionic/active ester block polymers (pSBMA-b-pNHSMA) with an identical pNHSMA segment (polymerization degree of 15) but varied zwitterionic pSBMA segments (polymerization degrees of 40 and 100) were precisely prepared. The pSBMA-b-pNHSMA block polymers could be easily covalently constructed on PU substrates that were pretreated with a polydopamine coating based on highly efficient anime-active ester chemistry, as evidenced by the water contact angle and XPS tests. The relationship between the length of pSBMA segments in the coating and the antifouling ability of PU substrates was established. The results indicated that block polymers with a pSBMA segment of 40 repeat units could significantly prevent protein adsorption, bacterial/platelet adhesion, and cell attachment on PU substrates within 24 h, while a longer pSBMA segment (repeat units of 100) could endow long-term antibacterial (14 days without biofilm formation) and anti-cell attachment (5 days without cell attachment) properties to the PU substrates. Furthermore, the coating significantly improved the surface lubricating property of PU substrates without compromising on the mechanical property. This strategy may find many applications in PU-based implants and devices.

In situ mineralized PLGA/zwitterionic hydrogel composite scaffold enables high-efficiency rhBMP-2 release for critical-sized bone healing.

Osteoconductive and osteoinductive scaffolds are highly desirable for functional restoration of large bone defects. Here, we report an in situ mineralized poly(lactic-co-glycolic acid)/poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide hydrogel (PLGA/PSBMA) scaffold as a novel high-efficiency carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) for bone tissue regeneration. By virtue of the oppositely charged structure, the zwitterionic PSBMA component is able to template well-integrated dense mineralization of calcium phosphate throughout the PLGA/PSBMA scaffold. The high affinity between rhBMP-2 and the mineralized matrix, combined with the capability of the zwitterionic hydrogel to sequester and to enable sustained release of ionic proteins, endows the mineralized PLGA/PSBMA scaffolds with high-efficiency sustained release of rhBMP-2 (only 1.7% release within 35 days), thus enabling robust healing of critical-sized (5 mm) nonunion calvarial defects in rats at an ultralow dosage of rhBMP-2 (150 ng per scaffold), at which level successful healing of critical-sized bone defects has never been reported. These findings show that the mineralized PLGA/PSBMA scaffold is promising for bone defect repair.

Mussel-inspired extracellular matrix-mimicking hydrogel scaffold with high cell affinity and immunomodulation ability for growth factor-free cartilage regeneration.

Background: Injury to articular cartilage cause certain degree of disability due to poor self-repair ability of cartilage tissue. To promote cartilage regeneration, it is essential to develop a scaffold that properly mimics the native cartilage extracellular matrix (ECM) in the aspect of compositions and functions. Methods: A mussel-inspired strategy was developed to construct an ECM-mimicking hydrogel scaffold by incorporating polydopamine-modified hyaluronic acid (PDA/HA) complex into a dual-crosslinked collagen (Col) matrix for growth factor-free cartilage regeneration. The adhesion, proliferation, and chondrogenic differentiation of cells on the scaffold were examined. A well-established full-thickness cartilage defect model of the knee in rabbits was used to evaluated the efficacy and functionality of the engineered Col/PDA/HA hydrogel scaffold. Results: The PDA/HA complex incorporated-hydrogel scaffold with catechol moieties exhibited better cell affinity than bare negatively-charged HA incorporated hydrogel scaffold. In addition, the PDA/HA complex endowed the scaffold with immunomodulation ability, which suppressed the expression of inflammatory cytokines and effectively activated the polarization of macrophages toward M2 phenotypes. The in vivo results revealed that the mussel-inspired Col/PDA/HA hydrogel scaffold showed strong cartilage inducing ability to promote cartilage regeneration. Conclusions: The PDA/HA complex-incorporated hydrogel scaffold overcame the cell repellency of negatively-charged polysaccharide-based scaffolds, which facilitated the adhesion and clustering of cells on the scaffold, and therefore enhanced cell-HA interactions for efficient chondrogenic differentiation. Moreover, the hydrogel scaffold modulated immune microenvironment, and created a regenerative microenvironment to enhance cartilage regeneration. The translational potential of this article: This study gives insight into the mussel-inspired approach to construct the tissue-inducing hydrogel scaffold in a growth-factor-free manner, which show great advantage in the clinical treatment. The hydrogel scaffold composed of collagen and hyaluronic acid as the major component, providing cartilage ECM-mimicking environment, is promising for cartilage defect repair.

Layer-by-layer construction of zwitterionic/biguanide polymers on silicone rubber as an antifouling and bactericidal coating.

Biofilm formation on biomedical devices is a major cause of device-associated infection. Traditional antibiotic treatment for biofilm-associated infection increases the risk of multidrug resistance. Thus, there is an urgent need to develop antibiotic-free strategies to prevent biofilm formation on biomedical devices. Herein, we report a layer-by-layer strategy to construct an antifouling and bactericidal dual-functional coating for silicone rubber (SR)-based substrates. Five zwitterionic active ester copolymers, p(SBMA-co-NHSMA), with varied zwitterionic pSBMA components that ranged from 50 to 90% (molar ratio) were precisely prepared. Based on -NH2/NHS chemistry, a zwitterionic pSBMA antifouling coating was successfully constructed on an -NH2-activated SR surface, while a biguanide polymer (PHMB) bactericidal coating was consequently tethered. The relationship between the composition of the polymeric coating and the overall antibacterial property (antifouling and bactericidal) that was endowed to the SR surface was established. The in vitro and in vivo results consistently showed that the optimal p(SBMA-co-NHSMA) copolymer (SBMA/NHSMA with molar percentage of 70/30) synergistically utilized antifouling and bactericidal abilities to endow a highly efficient overall antibacterial property (near 100% antibacterial ratios) to SR70-PHMB substrates without compromising cellular viability. This strategy may be applied to the many SR-based biomedical implants and devices where an antibacterial surface is required.

Zwitterionic/phosphonate copolymer coatings endow excellent antifouling properties and robust re-mineralization ability of dentine substrates.

Inhibition of biofilm formation and induction of the re-mineralization of damaged dental tissues are two major strategies to combat dental hypersensitivity (DH). However, single component synthetic materials normally cannot fulfil these two functions during the repairing of damaged dental tissues. Here, we report zwitterionic phosphorylcholine based polymers to be a new type of dual functional coating for the repairing of DH. Zwitterionic/phosphonate copolymers, p(DEMMP-co-MPC), bearing varied zwitterionic contents (95 and 75 mol%) were prepared through conventional radical copolymerization. 1H NMR spectroscopy clearly indicated the precise preparation of the copolymers. The copolymers can be easily coated on dentine substrates based on the high affinity between the phosphonate group and the calcium phosphate minerals of the dentine substrates, as evidenced by XPS and water contact angle measurements. Antifouling evaluations indicated that zwitterionic coating can efficiently inhibit protein adsorption (BSA, egg white, and milk, by 85%) and bacterial adhesion (by 97.1%) on dentine substrates. Furthermore, in vitro and in vivo experiments consistently indicated that the zwitterionic coating could not only induce the robust re-mineralization of dentine surfaces, but also template the extensive re-mineralization of dentine tubules to a similar level of pristine dentine. Both the antifouling properties and the re-mineralization potency are positively correlated with the content of zwitterionic pMPC in the coating copolymer. These findings may provide the zwitterionic phosphorylcholine based materials to be a promising candidate to treat dental hypersensitivity and other related dental diseases.

Poly(hexamethylene biguanide) (PHMB) as high-efficiency antibacterial coating for titanium substrates.

Bacterial associated infection is a remaining urgent challenge in clinic application of metallic implants and devices. Here, we developed a new strategy to combat the bacterial associated infection of titanium alloy (TC4). Novel phosphonate/active ester block polymers (pDEMMP-b-pNHSMA) with identical phosphonate segments (DP = 29) as the metal anchorable ligand but varied active ester segments (DPs = 7, 29, and 64) as the conjugation site for poly(hexamethylene biguanide) (PHMB) were precisely prepared. Through a facile two-step process, the polymeric coating were successfully constructed on TC4 substrates as evidenced by water contact angle and XPS measurements. Through systematical in vitro antibacterial evaluations, robust relationship between the chemical structure of coating polymer and the antibacterial property endowed to the TC4 substrates has been established. Results showed that the block polymer, bearing an active ester segment of 64 repeat units, enabled dense packing of PHMB coating on the TC4 surface, which is able to kill 100% of both S. aureus and E. coli. that seeded without compromising the cytocompatibility of TC4 substrates. Furthermore, PHMB coating could significantly inhibit the colony of the bacteria and consequently reduce the bacterial associated inflammatory reaction as verified by a subcutaneous infection model on rat.

Phosphonate/quaternary ammonium copolymers as high-efficiency antibacterial coating for metallic substrates.

Designing a coating material with efficient bactericidal property to cope with bacterial associated infections is highly desirable for metallic implants and devices. Here, we report phosphonate/quaternary ammonium copolymers, p(DEMMP-co-TMAEMA), as the new type of metal anchorable high-efficiency antibacterial coating. Seven p(DEMMP-co-TMAEMA) polymers with varied cationic components were precisely prepared via random radical polymerization. Copolymers were constructed on titanium alloy (TC4) substrates based on strong covalent bonding between the phosphonate group and metallic substrates through a one-step process as evidenced by XPS and water contact angle tests. A robust relationship between the composition of the copolymers and the bactericidal ability endowed to TC4 substrates was established. Results showed that the copolymer, with the pDEMMP content even as low as 6.3%, was able to anchor onto TC4 substrates. With the increase of cationic pTMAEMA content from 4.0 to 93.7% in the coating copolymer, the bactericidal ability endowed to the TC4 substrates was steadily increased from 39.4 to 98.8% for S. aureus and from 70.0 to 99.4% for E. coli after 8 h's of contacting. All p(DEMMP-co-TMAEMA) coating on TC4 substrates showed limited cytotoxicity to C2C12 cells. Notably, the phosphonate/quaternary amine copolymers can be easily constructed on diverse biomedical metals such as titanium (Ti), stainless steel (SS), and Ni/Cr alloys with significantly increased antibacterial performance, demonstrating the potency of the copolymer as the general high-efficiency antibacterial coating for diverse bio-metals.

Phosphonate/zwitterionic/cationic terpolymers as high-efficiency bactericidal and antifouling coatings for metallic substrates.

Bacteria associated infection is a critical challenge for metallic implants and devices in biomedical applications. Here, we report phosphonate/zwitterionic/quaternary amine terpolymers as a new type of antifouling and bactericidal coating for metallic substrates. Through reversible-addition fragmentation chain transfer polymerization (RAFT) and quaternization, well-controlled phosphonate/zwitterionic/cationic terpolymers with identical phosphonate segments (repeat units of 15) and varied zwitterionic and cationic components (nSBMA : nTMAEMA = 64 : 0, 54 : 18, 18 : 32, 9 : 52, and 0 : 70) were precisely prepared. The polymers can be coated on TC4 substrates based on the strong coordination between phosphonate groups and metallic substrates, as evidenced by water contact angle and XPS tests. Bactericidal evaluation revealed that the antibacterial efficiency was enhanced with the increase of cationic content in the coating polymers. TC4 substrates coated with the polymer coating with a cationic segment of 70 repeat units were able to kill 97.5 and 94.0% of S. aureus and E. coli, respectively. By virtue of the antifouling ability of the zwitterionic component and the bactericidal ability of the cationic component, the antibacterial efficiency was increased to 99.5% without significant compromising of the cytocompatibility. Meanwhile, the dual functional terpolymers could be easily applied on other metallic substrates, such as titanium, stainless steel, and Ni/Cr alloy, which were able to kill up to 97.9% of S. aureus and 99.9% of E. coli, respectively, endowing the excellent antibacterial properties to general bio-metals. The high-efficiency antibacterial modification strategy demonstrated here may find many applications on metallic implants and devices to combat bacterial associated infections.

Mussel-Inspired Redox-Active and Hydrophilic Conductive Polymer Nanoparticles for Adhesive Hydrogel Bioelectronics.

Conductive polymers (CPs) are generally insoluble, and developing hydrophilic CPs is significant to broaden the applications of CPs. In this work, a mussel-inspired strategy was proposed to construct hydrophilic CP nanoparticles (CP NPs), while endowing the CP NPs with redox activity and biocompatibility. This is a universal strategy applicable for a series of CPs, including polyaniline, polypyrrole, and poly(3,4-ethylenedioxythiophene). The catechol/quinone contained sulfonated lignin (LS) was doped into various CPs to form CP/LS NPs with hydrophilicity, conductivity, and redox activity. These CP/LS NPs were used as versatile nanofillers to prepare the conductive hydrogels with long-term adhesiveness. The CP/LS NPs-incorporated hydrogels have a good conductivity because of the uniform distribution of the hydrophilic NPs in the hydrogel network, forming a well-connected electric path. The hydrogel exhibits long-term adhesiveness, which is attributed to the mussel-inspired dynamic redox balance of catechol/quinone groups on the CP/LS NPs. This conductive and adhesive hydrogel shows good electroactivity and biocompatibility and therefore has broad applications in electrostimulation of tissue regeneration and implantable bioelectronics.

The characteristics of mussel-inspired nHA/OSA injectable hydrogel and repaired bone defect in rabbit.

With the rapid development of minimally invasive techniques in orthopedics, minimally invasive surgery combined with injection of bone repair materials has attracted increasing attention for the treatment of bone defects. Inspired by material in mussels, we decorated nanohydroxyapatite (nHA) with dopamine (DA) to form polydopamine (PDA)-decorated nHA (PHA). Then, we introduced PHA into a Schiff base reaction of oxidized sodium alginate (OSA) and gelatin (Gel) to prepare an injectable bone repair hydrogel under mild conditions. Subsequently, the injectability, morphology, mechanical, swelling, and degradation properties of the hydrogel were studied. Then, bone marrow mesenchymal stem cells (BMSCs) were cocultured with the hydrogels to investigate the cytotoxicity, proliferation, and osteogenic differentiation properties of the hydrogel. Finally, the bone repair ability of the OSA-Gel-PHA hydrogels was explored using a 12 weeks rabbit bone defect model. The results of tube inversion and rheological test showed that the hydrogel gelation time was 3-7 min, which will be suitable for clinical operation. The results of SEM, compression tests, rheological tests, swelling and degradation properties tests showed that the addition of PHA changed the microstructure of the hydrogels from porous structure to layered structure, not only improved the compressive strength, toughness, elastic modulus, storage modulus of the hydrogels, but also reduced the swelling properties and degradation rate of the hydrogels, making it more conducive to clinical operations. The results of laser confocal, MTT assay, alkaline phosphatase (ALP) assay and in vivo animal experiments showed that the addition of PHA not only nontoxic, but also promoted the adhesion, proliferation and osteogenic differentiation of BMSCs, as well as the repair and maturation of bone. The application of injectable bone repair materials not only solves the problem of bone defect filling, but also avoids a series of complications caused by open surgery, providing new method for the treatment of bone defects.

Mussel-inspired hybrid coating functionalized porous hydroxyapatite scaffolds for bone tissue regeneration.

The scaffold for bone tissue engineering should possess proper porosity, adequate mechanical properties, cell affinity for cell attachment, and the capability to bind bioactive agents to induce cell differentiation. In this study, we successfully prepared a porous hydroxyapatite (HA) scaffold that is functionalized by poly(L-lysine)/polydopamine (PLL/PDA) hybrid coating. The PLL/PDA coating takes advantages of the high protein and cell affinity of PDA, as well as the biodegradability of PLL. Therefore, the coating can anchor bone morphogenic protein-2 (BMP2) to the HA scaffold via catechol chemistry under a mild condition so as to protect the bioactivity of BMP2. Meanwhile, the coating can also release BMP2 in a tunable and sustainable manner as the PLL degrades in the physiological environment. The BMP2-entrapped PLL/PDA coating on the HA scaffold can more efficiently promote osteogenic differentiation of bone marrow stromal cells (BMSCs) in vitro and induce ectopic bone formation to a much greater level in vivo compared with a bare HA scaffold that delivers BMP2 in a burst manner. All of these results suggest that the PDA-mediated catechol modification of the HA scaffold can be an effective strategy to develop sustainable protein delivery system, and that the PLL/PDA-coated HA scaffold could be a promising candidate for bone tissue engineering applications.

Mussel-Inspired Tough Hydrogel with In Situ Nanohydroxyapatite Mineralization for Osteochondral Defect Repair.

Repairing osteochondral defects is a considerable challenge because it involves the breakdown of articular cartilage and underlying bone. Traditional hydrogels with a homogenized single-layer structure cannot fully restore the function of osteochondral cartilage tissue. In this study, a mussel-inspired hydrogel with a bilayer structure is developed to repair osteochondral defects. The hydrogel is synthesized by simultaneously polymerizing two layers using a one-pot method. The resulting upper and lower gelatin methacryloyl-polydopamine hydrogel layers are used as cartilage and subchondral bone repair layers, respectively. Polydopamine-induced hydroxyapatite in situ mineralization takes place in the lower layer to mimic the structure of subchondral bone. The bilayer hydrogel exhibits good mechanical properties for the synergistic effect of covalent and noncovalent bonds, as well as nanoreinforcement of mineralized hydroxyapatite. To improve the tissue-inducibility of hydrogels, transforming growth factor ß3 is immobilized in the upper layer to induce cartilage regeneration, while bone morphogenetic protein 2 is immobilized in the lower layer to induce bone regeneration. Bone and cartilage repair performance of the hydrogel is examined by implantation into a full-thickness cartilage defect of a rabbit knee joint. The bilayer-structure hydrogel promotes regeneration of osteochondral tissue, thus providing a new option for repair of osteochondral defects.

Plant-inspired adhesive and tough hydrogel based on Ag-Lignin nanoparticles-triggered dynamic redox catechol chemistry.

Adhesive hydrogels have gained popularity in biomedical applications, however, traditional adhesive hydrogels often exhibit short-term adhesiveness, poor mechanical properties and lack of antibacterial ability. Here, a plant-inspired adhesive hydrogel has been developed based on Ag-Lignin nanoparticles (NPs)triggered dynamic redox catechol chemistry. Ag-Lignin NPs construct the dynamic catechol redox system, which creates long-lasting reductive-oxidative environment inner hydrogel networks. This redox system, generating catechol groups continuously, endows the hydrogel with long-term and repeatable adhesiveness. Furthermore, Ag-Lignin NPs generate free radicals and trigger self-gelation of the hydrogel under ambient environment. This hydrogel presents high toughness for the existence of covalent and non-covalent interaction in the hydrogel networks. The hydrogel also possesses good cell affinity and high antibacterial activity due to the catechol groups and bactericidal ability of Ag-Lignin NPs. This study proposes a strategy to design tough and adhesive hydrogels based on dynamic plant catechol chemistry.