High-Strength, Biomimetic Functional Chitosan-Based Hydrogels for Full-Thickness Osteochondral Defect Repair

Fabrication of a hydrogel scaffold for full-thickness osteochondral defect repair remains a grand challenge. Developing layered and multiphasic hydrogels to mimic the intrinsic hierarchical structure of the osteochondral unit is a promising strategy. Chitosan-based hydrogels are widely applied for biomedical applications. However, insufficient mechanical strength and lack of biological cues to restore damaged cartilage and subchondral tissue significantly hinder their application in osteochondral tissue engineering. In this study, a strong and tough, osteochondral-mimicking functional chitosan-based hydrogel (bilayer-gel) with an in situ mineralized, osteoconductive lower layer and a basic fibroblast growth factor (bFGF)-incorporated, chondrogenic inducing upper layer was developed. The obtained bilayer-gel showed a depth-dependent gradient pore structure and composition. The strong double crosslinked hydrogel network and the homogeneous deposition of hydroxyapatite nanoparticles (HAp) at the lower layer provided a compressive strength of up to 2.5 MPa and a compressive strain of up to 40%. In vitro study showed that the bilayer-gel facilitates both chondrogenic differentiation in the upper layer and osteogenic differentiation in the lower layer. In vivo implantation revealed that the bilayer-gel could simultaneously promote hyaline cartilage and subchondral bone formation, thus resulting in an improved osteochondral reconstruction outcome. The present bilayer-gel thus shows great potential for full-thickness osteochondral defect repair

Cancellous-Bone-like Porous Iron Scaffold Coated with Strontium Incorporated Octacalcium Phosphate Nanowhiskers for Bone Regeneration

The repair of large bone defects poses a grand challenge in tissue engineering. Thus, developing biocompatible scaffolds with mechanical and structural similarity to human cancellous bone is in great demand. Herein, we fabricated a three-dimensional (3D) porous iron (Fe) scaffold with interconnected pores via a template-assisted electrodeposition method. The porous Fe scaffold with a skeleton diameter of 143 μm had the porosity >90%, an average pore size of 345 μm, and a yield strength of 3.5 MPa. Such structure and mechanical strength were close to those of cancellous bone. In order to enhance the biocompatibility of the scaffold, strontium incorporated octacalcium phosphate (Sr-OCP) was coated on the skeletons of the porous Fe scaffold. The coated Sr-OCP was in the form of nanowhiskers with a mean diameter of 300 nm and length of 30 μm. Such Sr-OCP coating could effectively reduce the release rate of the Fe ions to a level which was safe for the human body. Both in vitro cytotoxicity tests by extraction method and direct contact assay confirmed that the Sr-OCP coating could promote the cell adhesion and substantially enhance the biocompatibility of the porous Fe scaffolds. Thus, the cancellous-bone-like porous structure with compatible mechanical properties and excellent biocompatibility enables the present Sr-OCP coated porous Fe scaffold to be a promising candidate for bone repair and regeneration

Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole Nanofibrils

Conductive hydrogels are promising materials for soft electronic devices. To satisfy the diverse requirement of bioelectronic devices, especially those for human–machine interfaces, hydrogels are required to be transparent, conductive, highly stretchable, and skin-adhesive. However, fabrication of a conductive-polymer-incorporated hydrogel with high performance is a challenge because of the hydrophobic nature of conductive polymers making processing difficult. Here, we report a transparent, conductive, stretchable, and self-adhesive hydrogel by in situ formation of polydopamine (PDA)-doped polypyrrole (PPy) nanofibrils in the polymer network. The in situ formed nanofibrils with good hydrophilicity were well-integrated with the hydrophilic polymer phase and interwoven into a nanomesh, which created a complete conductive path and allowed visible light to pass through for transparency. Catechol groups from the PDA–PPy nanofibrils imparted the hydrogel with self-adhesiveness. Reinforcement by the nanofibrils made the hydrogel tough and stretchable. The proposed simple and smart strategy of in situ formation of conductive nanofillers opens a new route to incorporate hydrophobic and undissolvable conductive polymers into hydrogels. The fabricated multifunctional hydrogel shows promise in a range of applications, such as transparent electronic skins, wound dressings, and bioelectrodes for see-through body-adhered signal detection

Pulse Electrochemical Driven Rapid Layer-by-Layer Assembly of Polydopamine and Hydroxyapatite Nanofilms via Alternative Redox <i>in Situ</i> Synthesis for Bone Regeneration

Polydopamine (PDA) is an important candidate material for the surface modification of biomedical devices because of its good adhesiveness and biocompatibility. However, PDA nanofilms lack osteoinductivity, limiting their applications in bone tissue engineering. Hydroxyapatite nanoparticles (HA-NPs) are the major component of natural bone, which can be used to effectively enhance the osteoinductivity of PDA nanofilms. Herein, we developed a pulse electrochemical driven layer-by-layer (PED-LbL) assembly process to rapidly deposit HA-NPs and PDA (HA-PDA) multilayer nanofilms. In this process, PDA and HA-NPs are <i>in situ</i> synthesized in two sequential oxidative and reductive pulses in each electrochemical deposition cycle and alternately deposited on the substrate surfaces. PDA assists the <i>in situ</i> synthesis of HA-NPs by working as a template, which avoids the noncontrollable HA nucleation and aggregation. The HA-PDA multilayer nanofilms serve as a tunable reservoir to deliver bone morphogenetic protein-2 and exhibit high osteoinductivity both <i>in vitro</i> and <i>in vivo</i>. This PED-LbL assembly process breaks the limitation of traditional LbL assembly, allowing not only the rapid assembly of oppositely charged polyelectrolytes but also the <i>in situ</i> synthesis of organic/inorganic NPs that are uniformly incorporated in the nanofilm. It has broad applications in the preparation of versatile surface coatings on various biomedical devices

Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole Nanofibrils

Conductive hydrogels are promising materials for soft electronic devices. To satisfy the diverse requirement of bioelectronic devices, especially those for human–machine interfaces, hydrogels are required to be transparent, conductive, highly stretchable, and skin-adhesive. However, fabrication of a conductive-polymer-incorporated hydrogel with high performance is a challenge because of the hydrophobic nature of conductive polymers making processing difficult. Here, we report a transparent, conductive, stretchable, and self-adhesive hydrogel by in situ formation of polydopamine (PDA)-doped polypyrrole (PPy) nanofibrils in the polymer network. The in situ formed nanofibrils with good hydrophilicity were well-integrated with the hydrophilic polymer phase and interwoven into a nanomesh, which created a complete conductive path and allowed visible light to pass through for transparency. Catechol groups from the PDA–PPy nanofibrils imparted the hydrogel with self-adhesiveness. Reinforcement by the nanofibrils made the hydrogel tough and stretchable. The proposed simple and smart strategy of in situ formation of conductive nanofillers opens a new route to incorporate hydrophobic and undissolvable conductive polymers into hydrogels. The fabricated multifunctional hydrogel shows promise in a range of applications, such as transparent electronic skins, wound dressings, and bioelectrodes for see-through body-adhered signal detection

Bioadhesive Microporous Architectures by Self-Assembling Polydopamine Microcapsules for Biomedical Applications

Bioadhesive microporous architectures that mimic the functions of a natural extracellular matrix (ECM) were prepared by self-assembling polydopamine (PDA) microcapsules, which not only favor cell adhesion and growth, but also facilitate growth factor immobilization and release. PDA-coated polystyrene (PS) microspheres are synthesized by polymerization of dopamine on sulfonated PS microspheres and then assembled using positively charged chitosan (CHI) layers as link agents. After the PS core templates were removed, microporous architectures composed of PDA microcapsules were obtained. The produced microporous PDA architectures have a high capability of adsorbing BMP-2 and realize the sustained release of BMP-2. More importantly, the bioadhesive micro architecture and its immobilized BMP-2 synergistically enhance the activity and osteogenetic differentiation of bone marrow mesenchymal stem cells (BMSCs). Both supercell adhesion and BMP-2 immobilization ability of these architectures are attributed to the intrinsic adhesive nature of PDA and the porous architectures via the assembly of PDA microcapsules. The bioadhesive microporous PDA architectures with both cell affinitive and GF release features have a great potential to mimic natural ECM for modifying various medical devices in the fields of tissue engineering and regenerative medicine

Transparent, Adhesive, and Conductive Hydrogel for Soft Bioelectronics Based on Light-Transmitting Polydopamine-Doped Polypyrrole Nanofibrils

Conductive hydrogels are promising materials for soft electronic devices. To satisfy the diverse requirement of bioelectronic devices, especially those for human–machine interfaces, hydrogels are required to be transparent, conductive, highly stretchable, and skin-adhesive. However, fabrication of a conductive-polymer-incorporated hydrogel with high performance is a challenge because of the hydrophobic nature of conductive polymers making processing difficult. Here, we report a transparent, conductive, stretchable, and self-adhesive hydrogel by in situ formation of polydopamine (PDA)-doped polypyrrole (PPy) nanofibrils in the polymer network. The in situ formed nanofibrils with good hydrophilicity were well-integrated with the hydrophilic polymer phase and interwoven into a nanomesh, which created a complete conductive path and allowed visible light to pass through for transparency. Catechol groups from the PDA–PPy nanofibrils imparted the hydrogel with self-adhesiveness. Reinforcement by the nanofibrils made the hydrogel tough and stretchable. The proposed simple and smart strategy of in situ formation of conductive nanofillers opens a new route to incorporate hydrophobic and undissolvable conductive polymers into hydrogels. The fabricated multifunctional hydrogel shows promise in a range of applications, such as transparent electronic skins, wound dressings, and bioelectrodes for see-through body-adhered signal detection

DataSheet1_Mouse Strain– and Charge-Dependent Vessel Permeability of Nanoparticles at the Lower Size Limit.docx

Remarkable advancement has been made in the application of nanoparticles (NPs) for cancer therapy. Although NPs have been favorably delivered into tumors by taking advantage of the enhanced permeation and retention (EPR) effect, several physiological barriers present within tumors tend to restrict the diffusion of NPs. To overcome this, one of the strategies is to design NPs that can reach lower size limits to improve tumor penetration without being rapidly cleared out by the body. Several attempts have been made to achieve this, such as selecting appropriate nanocarriers and modifying surface properties. While many studies focus on the optimal design of NPs, the influence of mouse strains on the effectiveness of NPs remains unknown. Therefore, this study aimed to assess whether the vascular permeability of NPs near the lower size limit differs among mouse strains. We found that the vessel permeability of dextran NPs was size-dependent and dextran NPs with a size below 15 nm exhibited leakage from postcapillary venules in all strains. Most importantly, the leakage rate of 8-nm fluorescein isothiocyanate dextran was significantly higher in the BALB/c mouse strain than in other strains. This strain dependence was not observed in slightly positive TRITC-dextran with comparable sizes. Our results indicate that the influence on mouse strains needs to be taken into account for the evaluation of NPs near the lower size limit.</p

Biomimetic Mineralized Hierarchical Graphene Oxide/Chitosan Scaffolds with Adsorbability for Immobilization of Nanoparticles for Biomedical Applications

Biomimetic calcium phosphate mineralized graphene oxide/chitosan (GO/CS) scaffolds with hierarchical structures were developed. First, GO/CS scaffolds with large micropores (∼300 μm) showed high mechanical strength due to the electrostatic interaction between the oxygen-containing functional groups of GO and the amine groups of CS. Second, octacalcuim phosphate (OCP) with porous structures (∼1 μm) was biomimetically mineralized on the surfaces of the GO/CS scaffolds (OCP-GO/CS). The hierarchical microporous structures of OCP-GO/CS scaffolds provide a suitable environment for cell adhesion and growth. The scaffolds have exceptional adsorbability of nanoparticles. Bone morphogenetic protein-2 (BMP-2)-encapsulated bovine serum albumin (BSA) nanoparticles and Ag nanoparticles (Ag-NPs) were adsorbed in the scaffolds for enhancement of osteoinductivity and antibacterial properties, respectively. Antibacterial tests showed that the scaffolds exhibited high antibacterial properties against both Escherichia coli and Staphylococcus epidermidis. In vitro and in vivo experiments revealed that the scaffolds have good biocompatibility, enhanced bone marrow stromal cells proliferation and differentiation, and induced bone tissue regeneration. Thus, the biomimetic OCP-GO/CS scaffolds with immobilized growth factors and antibacterial agents might be excellent candidates for bone tissue engineering