Polysaccharide-Derived Ice Recrystallization Inhibitors with a Modular Design: The Case of Dextran-Based Graft Polymers.

Ice recrystallization inhibitors inspired from antifreeze proteins (AFPs) are receiving increasing interest for cryobiology and other extreme environment applications. Here, we present a modular strategy to develop polysaccharide-derived biomimetics, and detailed studies were performed in the case of dextran. Poly(vinyl alcohol) (PVA) which has been termed as one of the most potent biomimetics of AFPs was grafted onto dextran via thiol-ene click chemistry (Dex-g-PVA). This demonstrated that Dex-g-PVA is effective in IRI and its activity increases with the degree of polymerization (DP) (sizes of ice crystals were 18.846 ± 1.759 and 9.700 ± 1.920 µm with DPs of 30 and 80, respectively) and fraction of PVA. By means of the dynamic ice shaping (DIS) assay, Dex-g-PVA is found to engage on the ice crystal surfaces, thus the ice affinity accounts for their IRI activity. In addition, Dex- g-PVA displayed enhanced IRI activity compared to that of equivalent PVA alone. We speculate that the hydrophilic nature of dextran would derive PVA in a stretch conformation that favors ice binding. The modular design can not only offer polysaccharides IRI activity but also favor the ice-binding behavior of PVA.

Bio-Inspired Antibacterial Hydrogel Adhesives with High Adhesion Strength.

Traditional adhesives such as cyanoacrylate glue are mostly solvent-based. They are facing the problem of insufficient adhesion to some substrates, and also from the drawback of volatilization and release of small organic molecules in the process of usage. Therefore, a novel adhesive with non-irritating, high adhesive strength, and antibacterial properties is highly required. In this study, a full physically crosslinked zwitterionic poly(betaine sulfonate methacrylate) (PSBMA) hydrogel is proposed. The physical crosslinking interactions endow the hydrogel with good self-healing properties. Furthermore, the pure physical crosslinking hydrogel can form PSBMA powder adhesive after lyophilization and return to the hydrogel state after hydration. The mechanical properties of PSBMA adhesive can be modulated via adjusting the solid content and initiator dosage. Following the cure process similar to that of snail mucus or insect exoskeletons in nature, the adhesion of the PSBMA adhesive is improved at least 100 times than its wet state. In addition, the PSBMA adhesive is easy to be removed due to the dissociation of cross-linked structures in saltwater environments. Moreover, PSBMA adhesive with antifouling properties can effectively prevent the adhesion of proteins and bacteria, which shows potential applications in the assembly of medical devices.

Large-Scale Fabrication of Freestanding Polymer Ultrathin Porous Membranes for Transparent Transwell Coculture Systems.

Advancements in cell coculture systems with porous membranes have facilitated the simulation of human-like in vitro microenvironments for diverse biomedical applications. However, conventional Transwell membranes face limitations in low porosity (ca. 6%) and optical opacity due to their large thickness (ca. 10 µm). In this study, we demonstrated a one-step, large-scale fabrication of freestanding polymer ultrathin porous (PUP) membranes with thicknesses of hundreds of nanometers. PUP membranes were produced by using a gap-controlled bar-coating process combined with polymer blend phase separation. They are 20 times thinner than Transwell membranes, possessing 3-fold higher porosity and exhibiting high transparency. These membranes demonstrate outstanding molecular permeability and significantly reduce the cell-cell distance, thereby facilitating efficient signal exchange pathways between cells. This research enables the establishment of a cutting-edge in vitro cell coculture system, enhancing optical transparency, and streamlining the large-scale manufacturing of porous membranes.

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.

Synthesis of agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] zwitterionic graft copolymers via ATRP and their thermally-induced aggregation behavior in aqueous media.

A novel polysaccharide-based zwitterionic copolymer, agarose-graft-poly[3-dimethyl (methacryloyloxyethyl) ammonium propanesulfonate] (agarose-g-PDMAPS) with UCST, depending both on hydrogen bonding and electrostatic interaction, was synthesized by ATRP, and its aggregation behavior in aqueous media was investigated in detail. Proton nuclear magnetic resonance spectroscopy, Fourier transform-infrared spectroscopy, and gel-permeation chromatography were performed to characterize the copolymer. Thermosensitive behaviors of the copolymers in water, NaCl, and urea solution were tracked by ultraviolet, dynamic light scattering, and transmission electron microscopy analysis. It was found that the copolymers existed as "core-shell" spheres at an elevated temperature, as a result of the self-assembly of the agarose backbones located in the "core" driven by hydrogen-bonding interactions. When the copolymer solution was cooled below UCST, the core-shell spheres began to aggregate because of the electrostatic interactions and collapse of PDMAPS side chains in the "shell" layer. UCST of the copolymer could be tuned in a wide range, depending on the chain lengths of PDMAPS. This is the first example to investigate the thermosensitivity, combining ionic interactions of the zwitterionic side chains with hydrogen bondings from the biocompatible agarose backbones. The synthetic strategy presented here can be employed in the preparation of other novel biomaterials from a variety of polysaccharides.

Strongly adhesive zwitterionic composite hydrogel paints for surgical sutures and blood-contacting devices.

Hydrogels show eminent advantages in biomedical and pharmaceutical fields. However, their application as coating materials for biomedical devices is limited by several key challenges, such as lack of universality, weak mechanical strength, and low adhesion to the substrate. Here we report versatile and tough adhesion composite hydrogel paints (CHPs), which consist of zwitterionic copolymers and microgels, both with reactive groups. The CHPs exhibit tunable rheology and thickness, hydrophilicity, biofouling resistance, durability, and convenient fabrication on metal, polymer, and inorganic surfaces with arbitrary shapes. As a proof-of-concept, the CHP-surgical sutures demonstrate exceptional lubrication, drug delivery, anti-infection, and anti-fibrous capsule properties. Moreover, the CHP-PVC tubing effectively prevents thrombus formation in vitro and ex vivo rabbit blood circulation without anticoagulants. This work provides valuable insights for enhancing and developing integrated hydrogel technologies for biomedical devices. STATEMENT OF SIGNIFICANCE: The combination of hydrogel and biomedical devices can enable numerous existing applications in medicine. In this study, inspired by the principle of microgel reinforcement in industrial paints, we propose a simple and versatile zwitterionic composite hydrogel paints (CHPs) strategy, which can be easily applied to diverse substrates with arbitrary shapes by covalent grafting between complementary groups by brush, dip, or spray. The CHPs integrated universality, tough adhesion, mechanical durability, and anti-biofouling properties because of their unique chemical composition and coating structure design. This strategy provides a simple and versatile route for surface modification of biomedical devices.

A biocompatible cell cryoprotectant based on sulfoxide-containing amino acids: mechanism and application.

The preservation of cells at cryogenic temperatures requires the presence of cryoprotectants (CPAs). Dimethyl sulfoxide (DMSO), as a state-of-the-art CPA, is widely used for the storage of many types of cells. However, its intrinsic toxicity is still an obstacle for its applications in clinical practice. Herein, we report a DMSO analogue, L-methionine sulfoxide (Met(O)-OH), as a CPA for cell cryopreservation. The molecular-level cryopreservation roles of Met(O)-OH were investigated by experiments and molecular dynamics simulations. The results also found that Met(O)-OH showed high ice recrystallization inhibition (IRI) activity and the ice crystals in Met(O)-OH solution tend to be relatively round and smooth; moreover, the ice size was significantly reduced to 30.26 µm compared with pure water (135.87 µm) or DMSO solution (45.08 µm). At the molecular level, Met(O)-OH could stably bind the surface of the ice crystals and form more stable hydrogen bonds with ice compared with L-methionine. Moreover, Met(O)-OH could significantly reduce the damage to cells caused by osmotic shock and did not change the cell viability even at high concentration (4%). Based on these results, nucleated L929 cells and anuclear sheep red blood cells (SRBCs) were used as cell models to investigate the cryopreservation activity of Met(O)-OH. The results suggested that, under the optimum protocol, Met(O)-OH showed an effective post-thaw survival efficiency with ultrarapid freezing, and the post-thaw survival efficiency of L929 cells reached 84.0%. This work opens up the possibility for an alternative to traditional toxic CPA DMSO, and provides insights for the development of DMSO analogues with non-toxic/low toxicity for cell cryoprotection applications.

Preparation and characterization of a VEGF-Fc fusion protein matrix for enhancing HUVEC growth.

To enhance vascularization of hydrophobic implants in vivo, a VEGF-Fc fusion protein consisting of vascular endothelial growth factor (VEGF) fused to the immunoglobulin G Fc domain was prepared as an artificial extracellular matrix (ECM). VEGF-Fc was stably immobilized on a polystyrene plate due to the hydrophobicity of the Fc domain, and significantly enhanced the adhesion of human umbilical vein endothelial cells (HUVECs). Additionally, the use of VEGF-Fc as an ECM markedly promoted the proliferation of HUVECs longer than 72 h and induced the reorganization of actin filaments into larger stress fibers within these cells. The VEGF-Fc fusion protein may be a promising artificial ECM for enhancing endothelial cell growth.

Rational design of injectable conducting polymer-based hydrogels for tissue engineering.

Recently, injectable conducting polymer-based hydrogels (CPHs) have received increasing attention in tissue engineering owing to their controlled conductivity and minimally invasive procedures. Conducting polymers (CPs) are introduced into hydrogels to improve the electrical integration between hydrogels and host tissues and promote the repair of damaged tissues. Furthermore, endowing CPHs with in situ gelation or shear-thinning properties can reduce the injury size and inflammation caused by implanted surgery materials, which approaches the clinical transformation target of conductive biomaterials. Notably, functional CPs, including hydrophilic CP complexes, side-chain modified CPs, and conducting graft polymers, improve the water-dispersible and biocompatible properties of CPs and exhibit significant advantages in fabricating injectable CPHs under physiological conditions. This review discusses the recent progress in designing injectable hydrogels based on functional CPs. Their potential applications in neurological treatment, myocardial repair, and skeletal muscle regeneration are further highlighted. STATEMENT OF SIGNIFICANCE: Conducting polymer-based hydrogels (CPHs) have broad application prospects in the biomedical field. However, the low water dispersibility and processability of conducting polymers (CPs) make them challenging to form injectable CPHs uniformly. For the first time, this review summarizes the functionalization strategies to improve the hydrophilicity and biocompatibility of CPs, which provides unprecedented advantages for designing and fabricating the physical/chemical crosslinked injectable CPHs. Besides, future challenges and prospects for further clinical transformation of injectable CPHs for tissue engineering are presented. This review's content is of great significance for the treatment of electroactive tissues with limited self-regeneration, including neurological treatment, myocardial repair, and skeletal muscle regeneration.  Therefore, it is inspiring for the tissue engineering research of biomaterials and medical practitioners.

Bio-Inspired Instant Underwater Adhesive Hydrogel Sensors.

Underwater adhesion plays an essential role in soft electronics for the underwater interface. Although hydrogel-based electronics are of great interest, because of their versatility, water molecules prevent hydrogels from adhering to substrates, thus bottlenecking further applications. Herein, inspired by the barnacle proteins, MXene/PHMP hydrogels with strong repeatable underwater adhesion are developed through the random copolymerization of 2-phenoxyethyl acrylate, 2-methoxyethyl acrylate, and N-(2-hydroxyethyl) acrylamide with the presence of MXene nanosheets. The hydrogels are mechanically tough (elastic modulus of 32 kPa, fracture stress of 0.11 MPa), and 2-phenoxyethyl acrylate (PEA) with aromatic groups endows the hydrogel with nonswelling property and prevents water molecules from invading the adhesive interface, rendering the hydrogels an outstanding adhesive behavior toward various substrates (including glass, iron, polyethylene terephthalate (PET), porcine). Besides, dynamic physical interactions allow for instant and repeatable underwater adhesion. Furthermore, the MXene/PHMP hydrogels exhibit a high conductivity (0.016 S/m), fast responsiveness, and superior sensitivity as a strain sensor (gauge factor = 7.17 at 200%-500% strain) and pressure sensor (0.63 kPa-1 at 0-70 kPa). The underwater applications of bionic hydrogel-based sensors have been demonstrated, such as human motion, pressure sensing, and holding objects. It is anticipated that the instant and repeatable underwater adhesive hydrogel-based sensors extend the underwater applications of hydrogel electronics.

Bioinspired zwitterionic microgel-based coating: Controllable microstructure, high stability, and anticoagulant properties.

Zwitterionic polymers have shown promising results in non-fouling and preventing thrombosis. However, the lack of controlled surface coverage hinders their application for biomedical devices. Inspired by the natural biological surfaces, a facile zwitterionic microgel-based coating strategy is developed by the co-deposition of poly (sulfobetaine methacrylate-co-2-aminoethyl methacrylate) microgel (SAM), polydopamine (PDA), and sulfobetaine-modified polyethyleneimine (PES). The SAMs were used to construct controllable morphology by using the PDA combined with PES (PDAS) as the intermediate layer, which can be easily modulated via adjusting the crosslinking degree and contents of SAMs. The obtained SAM/PDAS coatings exhibit high anti-protein adhesive properties and can effectively inhibit the adhesion of cells, bacteria, and platelet through the synergy of high deposition density and controllable morphology. In addition, the stability of SAM/PDAS coating is improved owing to the anchoring effects of PDAS to substrate and SAMs. Importantly, the ex vivo blood circulation test in rabbits suggests that the SAM/PDAS coating can effectively decrease thrombosis without anticoagulants. This study provides a versatile coating method to address the integration of zwitterionic microgel-based coatings with high deposition density and controllable morphology onto various substrates for wide biomedical device applications. STATEMENT OF SIGNIFICANCE: Thrombosis is a major cause of medical device implantation failure, which results in significant morbidity and mortality. In this study, inspired by natural biological surfaces (fish skin and vascular endothelial layer) and the anchoring ability of mussels, we report a convenient and efficient method to firmly anchor zwitterionic microgels using an oxidative co-deposition strategy. The prepared coating has excellent antifouling and antithrombotic properties through the synergistic effect of physical morphology and chemical composition. This biomimetic surface engineering strategy is expected to provide new insights into the clinical problems of blood-contacting devices related to thrombosis.

An Intrapericardial Injectable Hydrogel Patch for Mechanical-Electrical Coupling with Infarcted Myocardium.

Although hydrogel-based patches have shown promising therapeutic efficacy in myocardial infarction (MI), synergistic mechanical, electrical, and biological cues are required to restore cardiac electrical conduction and diastolic-systolic function. Here, an injectable mechanical-electrical coupling hydrogel patch (MEHP) is developed via dynamic covalent/noncovalent cross-linking, appropriate for cell encapsulation and minimally invasive implantation into the pericardial cavity. Pericardial fixation and hydrogel self-adhesiveness properties enable the MEHP to highly compliant interfacial coupling with cyclically deformed myocardium. The self-adaptive MEHP inhibits ventricular dilation while assisting cardiac pulsatile function. The MEHP with the electrical conductivity and sensitivity to match myocardial tissue improves electrical connectivity between healthy and infarcted areas and increases electrical conduction velocity and synchronization. Overall, the MEHP combined with cell therapy effectively prevents ventricular fibrosis and remodeling, promotes neovascularization, and restores electrical propagation and synchronized pulsation, facilitating the clinical translation of cardiac tissue engineering.

Microgel reinforced zwitterionic hydrogel coating for blood-contacting biomedical devices.

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices.

Simultaneous engineering of nanofillers and patterned surface macropores of graphene/hydroxyapatite/polyetheretherketone ternary composites for potential bone implants.

Incorporating bioactive nanofillers and creating porous surfaces are two common strategies used to improve the tissue integration of polyetheretherketone (PEEK) material. However, few studies have reported the combined use of both strategies to modify PEEK. Herein, for the first time, dual nanoparticles of graphene oxide (GO) and hydroxyapatite (HAp) were incorporated into PEEK matrix to obtain ternary composites that were laser machined to create macropores with diameters ranging from 200 µm to 600 µm on the surfaces. The surface morphology and chemistry, mechanical properties, and cellular responses of the composites were investigated. The results show that micropatterned pores with a depth of 50 µm were created on the surfaces of the composites, which do not significantly affect the mechanical properties of the resultant composites. More importantly, the incorporation of GO and HAp significantly improves the cell adhesion and proliferation on the surface of PEEK. Compared to the smooth surface composite, the composites with macroporous surface exhibit markedly enhanced cell viability. The combined use of nanofillers and surface macropores may be a promising way of improving tissue integration of PEEK for bone implants.

Fabrication of Robust, Shape Recoverable, Macroporous Bacterial Cellulose Scaffolds for Cartilage Tissue Engineering.

Recently, the fabricating of three-dimensional (3D) macroporous bacterial cellulose (MP-BC) scaffolds with mechanically disintegrated BC fragments has attracted considerable attention. However, the successful implementation of these materials depends mainly on their mechanical stability and robustness. Here, a non-toxic crosslinker, 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS), is employed to induce crosslinking reactions between BC fragments. In addition to their large pore sizes, the EDC/NHS-crosslinked MP-BC scaffolds exhibit excellent compression properties and shape recovery ability, owing to the EDC/NHS-induced crosslinking on the BC nanofibers. The results of in vitro studies reveal that the biocompatibility of MP-BC scaffolds is better than that of pristine BC scaffolds because the former provided more space for cell proliferation. The results of in vivo studies show that the neocartilage tissue with native cartilage appearance and abundant cartilage-specific extracellular matrix deposition is successfully regenerated in nude mice. The findings reveal the immense application potential of mechanically robust BC scaffolds with controllable pore sizes and shape-recoverable properties in tissue engineering.

Ultrathin, Strong, and Highly Flexible Ti3C2Tx MXene/Bacterial Cellulose Composite Films for High-Performance Electromagnetic Interference Shielding.

The fabrication of ultrathin films that are electrically conductive and mechanically strong for electromagnetic interference (EMI) shielding applications is challenging. Herein, ultrathin, strong, and highly flexible Ti3C2Tx MXene/bacterial cellulose (BC) composite films are fabricated by a scalable in situ biosynthesis method. The Ti3C2Tx MXene nanosheets are uniformly dispersed in the three-dimensional BC network to form a mechanically entangled structure that endows the MXene/BC composite films with excellent mechanical properties (tensile strength of 297.5 MPa at 25.7 wt % Ti3C2Tx) and flexibility. Importantly, a 4 µm thick Ti3C2Tx/BC composite film with 76.9 wt % Ti3C2Tx content demonstrates a specific EMI shielding efficiency of 29141 dB cm2 g-1, which surpasses those of most previously reported MXene-based polymer composites with similar MXene contents and carbon-based polymer composites. Our findings show that the facile, environmentally friendly, and scalable fabrication method is a promising strategy for producing ultrathin, strong, and highly flexible EMI shielding materials such as the freestanding Ti3C2Tx/BC composite films for efficient EMI shielding to address EMI problems of a fast-developing modern society.

Improved Removal of Toxic Metal Ions by Incorporating Graphene Oxide into Bacterial Cellulose.

The efficient removal of toxic metal ions from waste water is of critical importance in environmental protection. In this study, we report the incorporation of graphene oxide (GO) into bacterial cellulose (BC) and the effect on the removal of metal ions from waste water. The as-prepared BC/GO adsorbents have a three-dimensional (3D) network structure with interconnected pores and high porosity. The adsorption capacities and efficiencies of the BC/GO adsorbents with varying GO contents were compared by using Cu2+, Cd2+, and Pb2+ as model heavy metal ions. The incorporated GO into the BC/GO adsorbents plays a critical role in removing metal ions through strong electrostatic interactions between the positive metal ions and the negative functional groups on GO. In addition, the effects of pH, contact time, adsorbent dose, and ion concentration on the adsorption behavior of the BC/GO adsorbents were investigated. The data from adsorption kinetics indicate that the adsorption of Cu2+, Cd2+, and Pb2+ on BC/GO obeys a pseudo-second-order model, while the adsorption isotherms vary with the type of metal ions. The desorption and readsorption experiments of the BC/GO adsorbents demonstrate good recyclability. It has been demonstrated that incorporating GO into BC is an effective way to improve the adsorption behavior of BC.

Carbon Nanotubes/Hydrophobically Associated Hydrogels as Ultrastretchable, Highly Sensitive, Stable Strain, and Pressure Sensors.

Conductive hydrogels have become one of the most promising materials for skin-like sensors because of their excellent biocompatibility and mechanical flexibility. However, the limited stretchability, low toughness, and fatigue resistance lead to a narrow sensing region and insufficient durability of the hydrogel-based sensors. In this work, an extremely stretchable, highly tough, and anti-fatigue conductive nanocomposite hydrogel is prepared by integrating hydrophobic carbon nanotubes (CNTs) into hydrophobically associated polyacrylamide (HAPAAm) hydrogel. In this conductive hydrogel, amphiphilic sodium dodecyl sulfate was used to ensure uniform dispersion of CNTs in the hydrogel network, and hydrophobic interactions between the hydrogel matrix and the CNT surface formed, greatly improving the mechanical properties of the hydrogel. The obtained CNTs/HAPAAm hydrogel showed excellent stretchability (ca. 3000%), toughness (3.42 MJ m-3), and great anti-fatigue property. Moreover, it exhibits both high tensile strain sensitivity in the wide strain ranges (gauge factor = 4.32, up to 1000%) and high linear sensitivity (0.127 kPa-1) in a large-pressure region within 0-50 kPa. The CNTs/HAPAAm hydrogel-based sensors can sensitively and stably detect full-range human activities (e.g., elbow rotation, finger bending, swallowing motion, and pronouncing) and handwriting, demonstrating the CNTs/HAPAAm hydrogel's potential as the wearable strain and pressure sensors for flexible devices.

Interpenetrated nano- and submicro-fibrous biomimetic scaffolds towards enhanced mechanical and biological performances.

Developing fibrous scaffolds with hierarchical structures that closely mimic natural extracellular matrix (ECM) is highly desirable. However, fabricating scaffolds with true nanofibers (<100 nm) and submicrofibers (<1 µm) remains a big challenge. In this work, to mimic the fibrillar structure of natural ECM, bacterial cellulose (BC) nanofibers were hybridized with cellulose acetate (CA) submicrofibers for the first time. The interpenetrated nano-submicron fibrous BC/CA scaffold was fabricated using the combined electrospinning and modified in situ biosynthesis method. The BC/CA scaffold has an integrated symmetrical nanostructure in which BC nanofibers (42 nm in diameter) penetrate into the submicrofibrous CA (820 nm in diameter) scaffold. The BC/CA scaffold shows an interconnected porous structure with a high porosity of >90%. Additionally, the combination of CA submicrofibers with BC nanofibers leads to significantly improved mechanical properties over nanofibrous BC and submicrofibrous CA scaffolds and enlarged pores over nanofibrous BC scaffold. In addition, the biological behaviors of prepared BC/CA on MC3T3-E1 cells were investigated. Results suggested that BC/CA scaffold is beneficial for cell migration and proliferation. Moreover, the BC/CA scaffold shows higher alkaline phosphatase (ALP) activity, and calcium depositions. In addition, the hierarchical structures can effectively improve the expression of osteogenic gene (ALP mRNA and Runx2 mRNA) and protein (ALP). We believe that the methodology might provide biomimetic morphological microenvironments for enhanced tissue regeneration.

Fully physically crosslinked pectin-based hydrogel with high stretchability and toughness for biomedical application.

Hydrogels derived from natural polymers have been extensively investigated in the biomedical field, while inherent brittleness and poor stability limit their applications. In this study, a tough pectin-Fe3+/poly (acrylamide-co-stearyl methacrylate) (P(AAm-co-SMA)) double physical crosslinking (DPC) network hydrogel is prepared using a three-step method. The first HPAAm network is formed via hydrophobic associations among the PSMA segment in P(AAm-co-SMA), and trivalent ions (Fe3+) crosslinked pectin network as the second network. Due to the reversibility of dual physical cross-linking structures, the pectin-Fe3+/HPAAm hydrogel exhibit excellent toughness (1.04-11.20 MJ m-3). In addition, the pectin-Fe3+/HPAAm DPC hydrogels have tunable mechanical properties (tensile strength: 0.97-1.61 MPa, elongation: 133-1346%, elastic modulus: 0.30-2.20 MPa) via adjusting the ratio of pectin network and HPAAm network. To explore their potential application in tissue engineering, ATDC5 chondrocytes were seeded on the prepared DPC hydrogels. Results suggest that the pectin-Fe3+/HPAAm DPC hydrogels can support the adhesion and proliferation of ATDC5, moreover, the ATDC5 cells can penetrate into the hydrogel. It is concluded that the prepared hydrogels exhibit potential application in the load-bearing tissue repair field.