Regulation of astrocyte activity and immune response on graphene oxide-coated titanium by electrophoretic deposition.

Introduction: Astrocytes play crucial role in modulating immune response in the damaged central nervous system. Numerous studies have investigated the relationship between immune responses in astrocytes and brain diseases. However, the potential application of nanomaterials for alleviating neuroinflammation induced by astrocytes remains unexplored. Method: In this study, we utilized electrophoretic deposition (EPD) to coat graphene oxide (GO) onto titanium (Ti) to enhance the bioactivity of Ti. Results: We confirmed that GO-Ti could improve cell adhesion and proliferation of astrocytes with upregulated integrins and glial fibrillary acidic protein (GFAP) expression. Moreover, we observed that astrocytes on GO-Ti exhibited a heightened immune response when exposed to lipopolysaccharide (LPS). Although pro-inflammatory cytokines increased, anti-inflammatory cytokines and brain-derived neurotrophic factors involved in neuroprotective effects were also augmented through nuclear localization of the yes-associated protein (YAP) and nuclear factor kappa B (NF-κB). Discussion: Taken together, GO-Ti could enhance the neuroprotective function of astrocytes by upregulating the expression of anti-inflammatory cytokines and neuroprotective factors with improved cell adhesion and viability. Consequently, our findings suggest that GO-Ti has the potential to induce neuroprotective effects by regulating cell activity.

Injectable remodeling hydrogels derived from alendronate-tethered alginate calcium complex for enhanced osteogenesis.

A combination of hydrogel materials, and therapeutic agents have been actively reported to facilitate bone defect healing. However, conventionally hydrogels using cross-linker would result in low stability of the hydrogel itself, loss of agents during cross-linking, and complexity of use. In this study, alendronate was tethered to an AlA to improve its bone healing and drug-loading stability. AlA was further functionalized with Ca2+ (AlACa). A mixture of AlACa and alginate formed AlAA hydrogel. The gelation time of AlAA was sufficient for injecting into the defect site. The hydrogel stiffness was controlled, while the stress-relaxation time was fixed. In vitro cell tests demonstrated that the AlAA promoted proliferation and differentiation behaviors. In particular, AlAA showed the best mechanical stiffness with appropriate stress-relaxation and cellular behavior, indicating that it would be beneficial as a scaffold in the bone tissue engineering field.

Correction: Oh et al. Enhanced Effect of Polyethyleneimine-Modified Graphene Oxide and Simvastatin on Osteogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells. Biomedicines 2021, 9, 501.

Jeong-Sun Park was not included as an author in the original publication [...].

Enhanced Effect of Polyethyleneimine-Modified Graphene Oxide and Simvastatin on Osteogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells.

Statin derivatives traditionally have been used for the treatment of hyperlipidemia, but recent studies have shown their ability to regulate bone metabolism and promote bone growth. In this study, simvastatin (Sim), a new therapeutic candidate for bone regeneration, was combined with graphene oxide (GO), which has recently attracted much interest as a drug delivery method, to produce a compound substance effective for bone regeneration. To create a stable and homogenous complex with Sim, GO was modified with polyethylenimine, and the effect of modification was analyzed using Fourier transform infrared spectroscopy, zeta potential, and cytotoxicity testing. More specifically, the osteogenic differentiation potential expected by the combination of the two effective materials for osteogenic differentiation, GO and Sim, was evaluated in mesenchymal stem cells. Compared with control groups with GO and Sim used separately, the GO/Sim complex showed excellent osteogenic differentiation properties, with especially enhanced effects in the complex containing < 1 µM Sim.

Engineered dressing of hybrid chitosan-silica for effective delivery of keratin growth factor and acceleration of wound healing.

Biological dressings composed of multi-components including extracellular matrix (ECM) materials and therapeutic agents for facilitating wound healing have been actively reported. To improve the wound healing ability of chitosan dressing, sol-gel derived silica was incorporated with chitosan and this chitosan-silica hybrid dressing was combined with keratinocyte growth factor (KGF) in this study. Such hybrid dressing showed higher efficacy of KGF adsorption than pure chitosan dressing due to its porous structure and hydrophilic character. The hybrid dressing showed sustainable release profile for KGF. The delivered-KGF improved keratinocyte activities such as attachment and proliferation. In vivo animal test using excisional wound model revealed that such dressing could facilitate skin regeneration. However, the tissue regeneration process was different depending on combinatorial components in the dressing. Chitosan dressing incorporated with KGF improved the wound healing process compared to chitosan dressing without KGF. The chitosan-silica hybrid dressing combined with KGF showed the best wound healing process.

Facile in situ formation of hybrid gels for direct-forming tissue engineering.

Development of bioactive hydrogel as extracellular matrix (ECM) is a very important field for cell-based therapy. In this study, we provided a facile method based on sol-gel process for fabricating bioactive composite hydrogels. The composite hydrogels were composed of sol-gel derived silica and biopolymer. Different amounts of silica solution (20-80wt%) were mixed with 2% polymer sol (alginate) followed by aging and gelation to form a network so that the alginate-silica hybrid mixture could form a gel without any additional crosslinking process. The self-gelation time of the hybrid hydrogel measured by rheometer was reduced as the content of silica was increased. Such hydrogels had highly porous and interconnected structures. Their strut showed uniform surface texture. Under physiological conditions (PBS, 37°C), these hybrid hydrogels exhibited long-term stability compared to alginate hydrogels as control. The mechanical properties of these hydrogels such as compressive strength, compressive modulus, and work of fracture were significantly enhanced by hybridization with sol-gel derived silica. In vitro cell tests revealed that these hybrid hydrogels exhibited improved cell adhesion and proliferation behaviors compared to pure alginate hydrogel cross-linked by CaCl2 solution. Furthermore, cell encapsulation within these hydrogels revealed that their alginate-silica composite provided suitable microenvironment for cell survival.