Photothermal driven BMSCs osteogenesis and M2 macrophage polarization on polydopamine-coated TiC nanosheets/poly(vinylidene fluoride trifluoroethylene) nanocomposite coatings.

Mild thermal stimulation plays an active role in bone tissue repair and regeneration. In this work, a bioactive polydopamine/TiC/poly(vinylidene fluoride trifluoroethylene) (PDA/TiC/P(VDF-TrFE)) nanocomposite coating with excellent near-infrared light (NIR)-triggered photothermal effect was designed to improve the osteogenic ability of implants. By incorporating dopamine (DA)-modified TiC nanosheets into the P(VDF-TrFE) matrix and combining them with alkali initiated in situ polymerization, the resulting PDA/TiC/P(VDF-TrFE) nanocomposite coating gained high adhesion strength on Ti substrate, excellent tribological and corrosion resistance properties, which was quite important for clinical application of implant coatings.

Accelerated Bone Regeneration on the Metal Surface through Controllable Surface Potential.

Surface potential is rarely investigated as an independent factor in influencing tissue regeneration on the metal surface. In this work, the surface potential on the titanium (Ti) surface was designed to be tailored and adjusted independently, which arises from the ferroelectricity and piezoelectricity of poled poly(vinylidene fluoride-trifluoroethylene) (PVTF). Notably, it is found that such controllable surface potential on the metal surface significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro as well as bone regeneration in vivo.

Regulation of Macrophage Polarization on Chiral Potential Distribution of CFO/P(VDF-TrFE) Films.

Surface potentials of biomaterials have been shown to regulate cell fate commitment. However, the effects of chirality-patterned potential distribution on macrophage polarization are still only beginning to be explored. In this work, we demonstrated that the chirality-patterned potential distribution of CoFeO/poly(vinylidene fluoride-trifluoroethylene) (CFO/P(VDF-TrFE)) films could significantly down-regulate the M1 polarization of bone marrow-derived macrophages (BMDMs).

Remote Activation of M2 Macrophage Polarization via Magneto-Mechanical Stimulation To Promote Osteointegration.

Osteoimmunomodulation has been considered to play a key role in osteointegration of orthopedic biomaterials. However, regulation of the macrophage phenotype in vivo with a spatiotemporal controllable way still remains a challenge. In this study, we designed a novel magnetic-responsive mineralized collagen coating to exert remotely controlled magneto-mechanical stimulation on macrophages using an external magnetic field.

Enhanced M2 Polarization of Oriented Macrophages on the P(VDF-TrFE) Film by Coupling with Electrical Stimulation.

Electrical stimulation (ES) has been considered a promising strategy in regulating intracellular communication, membrane depolarization, ion transport, etc. Meanwhile, cell topography, such as the alignment and elongation in anisotropic orientation, also plays a critical role in triggering mechanotransduction as well as the cellular fate. However, coupling of ES and cell orientation to regulate the polarization of macrophages is yet to be explored.

Photothermal extracellular matrix based nanocomposite films and their effect on the osteogenic differentiation of BMSCs.

Mild thermal stimulation could induce osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, nano-functionalized photothermal extracellular matrix (ECM) nanocomposite films were obtained through adding graphene during cell culture, so that graphene could directly integrate with the ECM secreted by cells. Owing to the similarity of the ECM to the microenvironment and the apparent photothermal effect of graphene nanoflakes, heat could be generated and transferred at the material-cell interface in a biomimetic way.

Electrochemical deposition of Ppy/Dex/ECM coatings and their regulation on cellular responses through electrical controlled drug release.

Bone tissue engineering requires a material that can simultaneously promote osteogenic differentiation and anti-inflammatory effects at specific times in response to a series of problems after bone implantation. In this study, the porous network-like titanium matrix was constructed and polypyrrole/dexamethasone (Ppy/Dex) composite coatings with three-dimensional nano-network structure were prepared by electrochemical deposition. The biocompatibility of the composite coatings was further improved by the composite of the extracellular matrix (ECM).

Polarized P(VDF-TrFE) film promotes skin wound healing through controllable surface potential.

Surface potential of biomaterials is found to be important for wound healing. Here, poly(vinylidenefluoride-co-trifluoroethylene) (P(VDF-TrFE)) films with different surface potentials and piezoelectric responses were prepared and explored for the effect of surface potential on wound healing. The crystalline state of P(VDF-TrFE) films were characterized with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transformed infrared spectroscopy (FTIR), illustrated that the electric polarization will promote the crystallization of the β phase of P(VDF-TrFE), in which the content of β phase increased from 82.

Dynamic photoelectrical regulation of ECM protein and cellular behaviors.

Dynamic regulation of cell-extracellular matrix (ECM)-material interactions is crucial for various biomedical applications. In this study, a light-activated molecular switch for the modulation of cell attachment/detachment behaviors was established on monolayer graphene (Gr)/n-type Silicon substrates (Gr/Si). Initiated by light illumination at the Gr/Si interface, pre-adsorbed proteins (bovine serum albumin, ECM proteins collagen-1, and fibronectin) underwent protonation to achieve negative charge transfer to Gr films (n-doping) through π-π interactions.

The osteogenic response to chirality-patterned surface potential distribution of CFO/P(VDF-TrFE) membranes.

Piezoelectric poly(vinylidene fluoride-trifluoroethylene) has demonstrated an ability to promote osteogenesis, and biomaterials with a chirality-patterned topological surface could enhance cellular osteogenic differentiation. In this work, we created a chirality-patterned surface potential distribution of CoFeO/poly(vinylidene fluoride-trifluoroethylene (CFO/P(VDF-TrFE)) membranes to explore their osteogenic response under no change in surface chemical and topology, attempting to further strengthen the ability of the membranes to promote osteogenesis. The chirality-patterned surface potential distribution was established by microdomain contact polarization with the help of sinistral/dextral-patterned ITO interdigital microelectrodes.

Photo-thermic mineralized collagen coatings and their modulation of macrophages polarization.

Macrophages polarization in bone immune microenvironment is crucial in bone regeneration. In this work, mineralized collagen (MC) coatings with photo-thermal effect were prepared through incorporation of polydopamine (PDA). MC coatings with different thicknesses were deposited on titanium substrate through electrochemical deposition.

Effects of electrical stimulation on cytokine-induced macrophage polarization.

Macrophages have two functionalized phenotypes, M1 and M2, and the regulation of M1/M2 polarization of macrophages is critical for tissue repair. Tissue-derived immune factors are considered the major drivers of macrophage polarization. Based on the main cytokine-induced polarization pathways, we tested the effect of electrical stimulation (ES) of macrophages on the regulation of M1/M2 polarization and a possible synergistic effect with the cytokines.

Anisotropic magneto-mechanical stimulation on collagen coatings to accelerate osteogenesis.

Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis.

Light-induced osteogenic differentiation of BMSCs with graphene/TiO composite coating on Ti implant.

Light-induced surface potential have been demonstrated as an effective bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation regulator. However, traditional bone repair implants almost were weak or no light-responsive. Fortunately, surface modification was a feasible strategy to realize its light functionalization for bone implants.

Enhanced osteogenic differentiation of mesenchymal stem cells on P(VDF-TrFE) layer coated microelectrodes.

Electrical stimulation has been proved to be critical to regulate cell behavior. But, cell behavior is also susceptible to multiple parameters of the adverse interferences such as surface current, electrochemical reaction products, and non-uniform compositions, which often occur during direct electric stimulation. To effectively prevent the adverse interferences, a novel piezoelectric poly(vinylidene fluoride-trfluoroethylene)(P(VDF-TrFE)) layer was designed to coat onto the indium tin oxide (ITO) planar microelectrode.

Gr/TiO Films with Light-Controlled Positive/Negative Charge for Cell Harvesting Application.

Light-induced cell harvest shows much potential in in vitro cell culture. In this work, a light-responsive monolayer graphene (Gr)/titanium dioxide nanodot (TN) film is designed and used for light-induced cell harvest. It is found that after 20 min of 365 nm UV or 450 nm visible light illumination, different types of cells could be detached from the surface effectively.

Polarization behavior of bone marrow-derived macrophages on charged P(VDF-TrFE) coatings.

The immune response of bone implants is closely related to the interaction between macrophages and biomaterial surfaces. In this work, the polarization behavior of mouse bone marrow-derived macrophages (BMDMs), including their morphology and expression of phenotypic markers, genes and cytokines, on charged surfaces with different potential intensities was systematically explored. We found that the charged surface could effectively promote BMDM polarization, and a higher potential intensity was conducive to the upregulation of the polarization of BMDMs into the M2 phenotype.

Enhancing osteogenic differentiation of BMSCs on high magnetoelectric response films.

High performance of biomaterial surfaces provides a sound basis to mediate cellular growth behavior. In this work, we attempted to incorporate both positive and negative magnetostriction particles of CoFeO (CFO) and TbDyFe alloy (TD) into piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for forming high magnetoelectric effect films, on which osteogenic differentiation could be dynamically mediated by a magnetic-field-induced surface potential (φ).The negatively poled film with TD/CFO volume ratio of 1:4 (1T4C) showed a highest magnetoelectric effect with φ of -171 mV at 2800 Oe.

Ultraviolet Radiant Energy-Dependent Functionalization Regulates Cellular Behavior on Titanium Dioxide Nanodots.

Titanium dioxide (TiO) photofunctionalization has been demonstrated as an effective surface modification method for the osseointegration of implants. However, the insufficient understanding of the mechanism underlying photofunctionalization limits its clinical applications. Here, we report an ultraviolet (UV) radiant energy-dependent functionalization on TiO nanodots (TN) surfaces.

Bioactive nanocomposite coatings under visible light illumination promoted surface-mediated gene delivery.

Gene delivery based on bioactive coatings on collagen has great potential for applications in bone repair. Meanwhile, controlled gene delivery at specific times/regions is essential for an efficient and complete bone reconstruction process. However, spatio-temporal regulation of gene release and delivery remains a great challenge.

Novel Platform for Surface-Mediated Gene Delivery Assisted with Visible-Light Illumination.

Surface-mediated gene delivery has attracted more and more attentions in biomedical research and applications because of its characteristics of low toxicity and localized delivery. Herein, a novel visible-light-regulated, surface-mediated gene-delivery platform is exhibited, arising from the photoinduced surface-charge accumulation on silicon. Silicon with a pn junction is used and tested subsequently for the behavior of surface-mediated gene delivery under visible-light illumination.

Periodic-Mechanical-Stimulus Enhanced Osteogenic Differentiation of Mesenchymal Stem Cells on FeO/Mineralized Collagen Coatings.

Mechanical stimulus has been demonstrated to be critical to stem cell fate commitment and tissue repair. However, it still remains a challenge to remote control of the mechanical stimulus acting on cells. Here, we designed a magnetic FeO/mineralized collagen coating on titanium substrate to regulate the osteogenic differentiation of mesenchymal stem cells (MSCs).

Controlled Release of Naringin in GelMA-Incorporated Rutile Nanorod Films to Regulate Osteogenic Differentiation of Mesenchymal Stem Cells.

Naringin, a Chinese herbal medicine, has been demonstrated to concentration-dependently promote osteogenic differentiation of mesenchymal stem cells (MSCs). However, it remains a challenge to load naringin on coatings for osteogenesis and further control the release kinetics. Here, we demonstrated that the release behavior of naringin on rutile nanorod films could be controlled by either mixing naringin with gelatin methacryloyl (GelMA) before spinning onto the films or soaking the obtained GelMA-incorporated films with the naringin solution to achieve the distinct degradation-type release and diffusion-type release, respectively.

KLF2 stemness maintains human mesenchymal stem cells in bone regeneration.

Mesenchymal stem cells (MSCs), which are undifferentiated stem cells with the property of stemness and the potential to differentiate into multiple lineages, including osteoblasts, have attracted a great deal of attention in bone tissue engineering. Consistent with the heterogeneity of MSCs, various surface markers have been used. However, it is still unclear which markers of MSCs are best for cell amplification in vitro and later bone regeneration in vivo.

Graphene/Si-Promoted Osteogenic Differentiation of BMSCs through Light Illumination.

Graphene (Gr) presents promising applications in regulating the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Light illumination is regarded as a spatiotemporally controllable, easily applicable, and noninvasive mean to modulate material responses. Herein, Gr-transferred silicon (Gr/Si) with a Schottky junction is utilized to evaluate the visible-light-promoted osteogenic differentiation of BMSCs.