Menghao Wang

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.

Computer simulation of biomolecule–biomaterial interactions at surfaces and interfaces

Biomaterial surfaces and interfaces are intrinsically complicated systems because they involve biomolecules, implanted biomaterials, and complex biological environments. It is difficult to understand the interaction mechanism between biomaterials and biomolecules through conventional experimental methods. Computer simulation is an effective way to study the interaction mechanism at the atomic and molecular levels. In this review, we summarized the recent studies on the interaction behaviors of biomolecules with three types of the most widely used biomaterials: hydroxyapatite (HA), titanium oxide (TiO2), and graphene(G)/graphene oxide(GO). The effects of crystal forms, crystallographic planes, surface defects, doping atoms, and water environments on biomolecules adsorption are discussed in detail. This review provides valuable theoretical guidance for biomaterial designing and surface modification.

Porous titanium scaffolds with self‐assembled micro/nano‐hierarchical structure for dual functions of bone regeneration and anti‐infection

Porous titanium (Ti) scaffolds are widely used for bone repair because of their good biocompatibility, mechanical properties, and corrosion resistance. However, pristine Ti scaffolds are bioinert and unable to induce bone regeneration. In this study, chitosan coated bovine serum albumin nanoparticles (CBSA NPs) and oxidized alginate (OSA) were in a layer-by-layer (LbL) manner on Ti scaffolds. The LbL film possessed micro/nano-hierarchical architectures, has the features of nanostructures, and possesses abundant functional groups from CBSA NPs and OSA to improve the surface biocompatibility and biofunctionality of Ti scaffolds. These groups provide active sites for stable and efficient immobilization of bone morphogenic protein-2 (BMP2) through chemical and physical interactions without compromising its bioactivity. The synergistic effect of the hierarchical structure of assembled films and immobilized BMP2 on the scaffold improves cell adhesion, proliferation, and induces osteogenic differentiation of bone marrow stromal cells in vitro. Moreover, this modification also enhances ectopic bone formation bone. Furthermore, grafting of vancomycin on OSA resulted in good antibacterial activity of Ti scaffolds for prevention of infection during the bone healing process. In summary, this NPs-assembling method is convenient and effective to produce nanostructures and to load growth factors and antibacterial agents into Ti scaffolds for bone tissue engineering.

Computer simulation of ions doped hydroxyapatite: A brief review

A brief review of commonly encountered anions, cations and co-doped HA and Ca-deficient HA was given in the DFT studies. First, the charge compensation mechanism, the preference substitution sites and crystal structure changes of doped HA were described and discussed. And then conclusions were drawn and future challenges were discussed. The review is expected to provide theoretical guidance for the development of bioactive HA with special structures and functions.

Effects of atomic-level nano-structured hydroxyapatite on adsorption of bone morphogenetic protein-7 and its derived peptide by computer simulation

Hydroxyapatite (HA) is the principal inorganic component of bones and teeth and has been widely used as a bone repair material because of its good biocompatibility and bioactivity. Understanding the interactions between proteins and HA is crucial for designing biomaterials for bone regeneration. In this study, we evaluated the effects of atomic-level nano-structured HA (110) surfaces on the adsorption of bone morphogenetic protein-7 (BMP-7) and its derived peptide (KQLNALSVLYFDD) using molecular dynamics and density functional theory methods. The results indicated that the atomic-level morphology of HA significantly affected the interaction strength between proteins and HA substrates. The interactions of BMP-7 and its derived peptide with nano-concave and nano-pillar HA surfaces were stronger than those with flat or nano-groove HA surfaces. The results also revealed that if the groove size of nano-structured HA surfaces matched that of residues in the protein or peptide, these residues were likely to spread into the grooves of the nano-groove, nano-concave, and nano-pillar HA, further strengthening the interactions. These results are helpful in better understanding the adsorption behaviors of proteins onto nano-structured HA surfaces, and provide theoretical guidance for designing novel bioceramic materials for bone regeneration and tissue engineering.

Mussel-inspired Dopamine Oligomer Intercalated Tough and Resilient Gelatin methacryloyl (GelMA) Hydrogels for Cartilage Regeneration

Gelatin methacryloyl (GelMA) hydrogels are widely used for tissue regeneration. Nonetheless, a pure GelMA hydrogel cannot efficiently serve for cartilage regeneration because of weak mechanical properties and brittleness. In this study, we established a mussel-inspired strategy for tuning the mechanical properties of GelMA hydrogels by intercalating oligomers of dopamine methacrylate (ODMA) into the chain of GelMA. After the ODMA intercalated, the hydrogel became tough and resilient. This is because ODMA intercalation reduces the high density of entangled GelMA chains and introduces additional sacrificial physical cross-linking into the hydrogel. Rheological analysis showed that the ODMA-GelMA hydrogel was mechanically stable at body temperature. The hydrogel also manifested a sustained protein release because of the ODMA catechol groups. Furthermore, the ODMA-GelMA hydrogel was found to have good biocompatibility and affinity for cells and tissues because of the catechol groups on ODMA. In vitro, the hydrogel promoted mesenchymal stem cell adhesion and growth, and in vivo, it promoted cartilage regeneration after loading with chondroitin sulfate or TGF-β3. The hydrogel can serve as a growth-factor-free scaffold for cartilage regeneration. This hydrogel not only provided a favorable microenvironment for cartilage repair but also could serve as a promising candidate material for repair of other tissues. This mussel-inspired strategy of introduction of reactive oligomers instead of polymers into a brittle hydrogel network may be extended to the development of other tough hydrogels for biomedical applications.

Resilient and flexible chitosan/silk cryogel incorporated with Ag/Sr co-doped nanoscale hydroxyapatite for osteoinductivity and antibacterial properties

Cryogels from natural biopolymers, especially chitosan (CS) and silk fibroin (SF), have attracted significant attention for bone tissue engineering due to their good biocompatibility and tissue affinity. However, they are still not widely applied in clinics because of their poor mechanical properties, and lack of osteoinductivity and antibacterial properties. Here, by integrating a physico-chemical hybrid-crosslinking strategy and a freeze-drying method, the authors have prepared a resilient and flexible chitosan/silk cryogel with Ag and Sr co-doped hydroxyapatite (AgSrHA). The cryogel exhibits super resilience and flexibility, which guarantees the mechanical strength required for bone repair. Furthermore, the cryogel possesses long-term effective antibacterial properties and osteoinductivity due to the slow release of Ag and Sr ions. The physico-chemical hybrid-crosslinking points were introduced into a CS/SF network by treating with a mixture of alkaline and polyethylene glycol glycidyl ether (PEGDE) at 60 °C, which endowed the cryogel with super resilience and flexibility. Nanoscale AgSrHA was incorporated into the CS/SF network to further enhance the mechanical properties of the cryogel. In addition, Ag and Sr were doped into the HA crystal lattice, which not only prevents cytotoxicity by avoiding the ion burst release behavior, but also can achieve antibacterial and osteoinductive properties for a long period of time. In short, the AgSrHA/CS/SF cryogel with excellent mechanical properties and long-term effective dual-biofunction of antibacterial properties and osteoinductivity would be an ideal candidate for successful bone repair in clinics.

Mussel-Inspired Tissue-Adhesive Hydrogel Based on the Polydopamine–Chondroitin Sulfate Complex for Growth-Factor-Free Cartilage Regeneration

Glycosaminoglycan-based hydrogels are widely used for cartilage repair because glycosaminoglycans are the main component of the cartilage extracellular matrix and can maintain chondrocyte functions. However, most of the glycosaminoglycan-based hydrogels are negatively charged and cell-repellant, and they cannot host cells or favor tissue regeneration. Inspired by mussel chemistry, we designed a polydopamine-chondroitin sulfate-polyacrylamide (PDA-CS-PAM) hydrogel with tissue adhesiveness and super mechanical properties for growth-factor-free cartilage regeneration. Thanks to the abundant reactive catechol groups on the PDA, a cartilage-specific PDA-CS complex was formed by the self-assembly of PDA and CS, and then the PDA-CS complex was homogenously incorporated into an elastic hydrogel network. This catechol-group-enriched PDA-CS complex endowed the hydrogel with good cell affinity and tissue adhesiveness to facilitate cell adhesion and tissue integration. Compared with bare CS, the PDA-CS complex in the hydrogel was more effective in exerting its functions on adhered cells to upregulate chondrogenic differentiation. Because of the synergistic effects of noncovalent interactions caused by the PDA-CS complex and covalently cross-linked PAM network, the hydrogel exhibited super resilience and toughness, meeting the mechanical requirement of cartilage repair. Collectively, this tissue-adhesive and tough PDA-CS-PAM hydrogel with good cell affinity creates a growth-factor-free and biomimetic microenvironment for chondrocyte growth and cartilage regeneration and sheds light on the development of growth-factor-free biomaterials for cartilage repair.

Conductive and Tough Hydrogels Based on Biopolymer Molecular Templates for Controlling in Situ Formation of Polypyrrole Nanorods

Conductive hydrogels (CHs) have gained significant attention for their wide applications in biomedical engineering owing to their structural similarity to soft tissues. However, designing CHs that combine biocompatibility with good mechanical and electrical properties is still challenging. Herein, we report a new strategy for the fabrication of tough CHs with excellent conductivity, superior mechanical properties, and good biocompatibility by using chitosan framework as molecular templates for controlling conducting polypyrrole (PPy) nanorods in situ formation inside the hydrogel networks. First, polyacrylamide/chitosan (CS) interpenetrating polymer network hydrogel was synthesized by UV photopolymerization; second, hydrophobic and conductive pyrrole monomers were absorbed and fixed on CS molecular templates and then polymerized with FeCl3 in situ inner hydrophilic hydrogel network. This strategy ensured that the hydrophobic PPy nanorods were uniformly distributed and integrated with the hydrophilic polymer phase to form highly interconnected conductive path in the hydrogel, endowing the hydrogel with high conductivity (0.3 S/m). The CHs exhibited remarkable mechanical properties after the chelation of CS by Fe3+ and the formation of composites with the PPy nanorods (fracture energy 12 000 J m-2 and compression modulus 136.3 MPa). The use of a biopolymer molecular template to induce the formation of PPy nanostructures is an efficient strategy to achieve conductive multifunctional hydrogels.

Interaction Behaviors of Fibrinopeptide-A and Graphene with Different Functional Groups: A Molecular Dynamics Simulation Approach

Graphene as a 2-dimentional material has been widely used in the field of biomedical applications. In this study, molecular dynamics simulations are carried out on the fibrinopeptide-A and graphene surfaces with N and O modifications. A new set of parameters for the CHARMM force field are developed to describe the behaviors of the surfaces. Our results indicate that the existence of most oxygen and nitrogen groups may enhance the interaction between the surfaces and the peptide, whereas the substitutional nitrogen on the graphene surface does not make a big difference. The improvement of interaction is not only because of the functional group on the surface, but also the defective morphology. The defective morphology also clears away the surface water layer. Our results suggest that the interactions between graphene biomolecules can be affected by functionalizing the surface with different types of functional groups, which is in accordance with the theory of material design.