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Flexible and Highly Biocompatible Nanofiber-Based Electrodes for Neural Surface Interfacing
Heo, Dong Nyoung,Kim, Han-Jun,Lee, Yi Jae,Heo, Min,Lee, Sang Jin,Lee, Donghyun,Do, Sun Hee,Lee, Soo Hyun,Kwon, Il Keun American Chemical Society 2017 ACS NANO Vol.11 No.3
<P>Polyimide (PI)-based electrodes have been widely used as flexible biosensors in implantable device appliCations for recording biological signals. However, the long-term quality of neural signals obtained from PI-based nerve electrodes tends to decrease due to nerve damage by neural tissue compression, mechanical mismatch, and insufficient fluid exchange between the neural tissue and electrodes. Here, we resolve these problems with a developed PI nanofiber (NF)-based nerve electrode for stable neural signal recording, which can be fabricated via electrospinning and inkjet printing. We demonstrate an NF-based nerve electrode that can be simply fabricated and easily applied due to its high permeability, flexibility, and biocompatibility. Furthermore, the electrode can record stable neural signals for extended periods of time, resulting in decreased mechanical mismatch, neural compression, and contact area. NF-based electrodes with highly flexible and body-fluid-permeable properties could enable future neural interfacing applications.</P>
Heo, Dong Nyoung,Ko, Wan-Kyu,Moon, Ho-Jin,Kim, Han-Jun,Lee, Sang Jin,Lee, Jung Bok,Bae, Min Soo,Yi, Jin-Kyu,Hwang, Yu-Shik,Bang, Jae Beum,Kim, Eun-Cheol,Do, Sun Hee,Kwon, Il Keun American Chemical Society 2014 ACS NANO Vol.8 No.12
<P>Gold nanoparticles (GNPs) have been previously reported to inhibit osteoclast (OC) formation. However, previous research only confirmed the osteoclastogenesis inhibitory effect under <I>in vitro</I> conditions. The aim of this study was to develop a therapeutic agent for osteoporosis based on the utilization of GNPs and confirm their effect both <I>in vitro</I> and <I>in vivo</I>. We prepared β-cyclodextrin (CD) conjugated GNPs (CGNPs), which can form inclusion complexes with curcumin (CUR–CGNPs), and used these to investigate their inhibitory effects on receptor activator of nuclear factor-κb ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs). The CUR–CGNPs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells in BMMs without inducing cytotoxicity. The mRNA expressions of genetic markers of OC differentiation including c-Fos, nuclear factor of activated T cells 1 (NFATc1), TRAP, and osteoclast associated receptor (OSCAR) were significantly decreased in the presence of CUR–CGNPs. In addition, the CUR–CGNPs inhibited OC differentiation of BMMs through suppression of the RANKL-induced signaling pathway. Additionally, CUR–CGNPs caused a decrease in RANKL-induced actin ring formation, which is an essential morphological characteristic of OC formation allowing them to carry out bone resorption activity. Furthermore, the <I>in vivo</I> results of an ovariectomy (OVX)-induced osteoporosis model showed that CUR–CGNPs significantly improved bone density and prevented bone loss. Therefore, CUR–CGNPs may prove to be useful as therapeutic agents for preventing and treating osteoporosis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2014/ancac3.2014.8.issue-12/nn504329u/production/images/medium/nn-2014-04329u_0017.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn504329u'>ACS Electronic Supporting Info</A></P>
Enhanced Biocompatibility of Polyimide Film by Anti-Inflammatory Drug Loading
Heo, Dong Nyoung,Ko, Wan-Kyu,Lee, Won Jun,Lee, Sang Jin,Lee, Donghyun,Heo, Min,Rim, Hyunjoon,Bae, Min Soo,Lee, Jung Bok,Ahn, Byung-Seob American Scientific Publishers 2016 Journal of Nanoscience and Nanotechnology Vol.16 No.8
<P>Polyimide (PI) has been used as a substructure in the electronics industry for several decades due to its excellent thermal, mechanical, and chemical properties as well as its relatively low dielectric constant. Micro-fabricated neural prosthetic devices, which are used for chronic recording and stimulation of nervous system tissues, are in the early stages of design and development. The interface between neural microelectrodes and neural tissue plays an important role in chronic in vivo recording. However, when these devices are implanted into brain tissue for long-term recording, they lose electrical connectivity due to immune response. To enhance biocompatibility of polyimide-based neural electrodes, we performed anti-inflammatory drug loading by soaking the PI in drug loaded solvent. The drug loaded PI films were subcutaneously implanted in a rat model. The biocompatibility of the PI film was analyzed using cytotoxicity assays, RT-PCR, and H&E staining. The solvent-extracted and drug loaded PI film shows better short term biocompatibility as compared to control and non-treated PI film. This anti-inflammatory drug loading method can be used to increase the biocompatibility of neural electrodes.</P>
Enhanced bone regeneration with a gold nanoparticle-hydrogel complex
Heo, Dong Nyoung,Ko, Wan-Kyu,Bae, Min Soo,Lee, Jung Bok,Lee, Deok-Won,Byun, Wook,Lee, Chang Hoon,Kim, Eun-Cheol,Jung, Bock-Young,Kwon, Il Keun The Royal Society of Chemistry 2014 Journal of Materials Chemistry B Vol.2 No.11
<P>Gold nanoparticles (GNPs) are widely used in diagnostics, drug delivery, biomedical imaging, and photo-thermal therapy due to their surface plasmon resonance, fluorescence, and easy-surface functionalization. According to recent studies, GNPs display a positive effect on the osteogenic differentiation of mesenchymal stem cells (MSCs) and MC3T3-E1 osteoblast-like cells. The aim of this study was to develop a new approach for bone tissue regeneration based on the utilization of a biodegradable hydrogel loaded with GNPs. We have used photo-curable gelatin hydrogels (Gel) in order to provide a proof of principle of GNPs in regeneration strategies for bone tissue repair. We have investigated the effects of these Gel-GNP composite hydrogels both <I>in vitro</I> and <I>in vivo</I>. The <I>in vitro</I> results showed that the hydrogels loaded with GNPs promote proliferation, differentiation, and alkaline phosphate (ALP) activities of human adipose-derived stem cells (ADSCs) as they differentiate towards osteoblast cells in a dose-dependent manner. Moreover, the <I>in vivo</I> results showed that these hydrogels loaded with high concentrations of GNPs had a significant influence on new bone formation. Through these <I>in vitro</I> and <I>vivo</I> tests, we found that the Gel-GNP can be a useful material for bone tissue engineering.</P>
Heo, Min,Lee, Sang Jin,Lee, Donghyun,Heo, Dong Nyoung,Lee, Jae Seo,Youn, Yun Hee,Lee, Si Eun,Ko, Na Re,Kim, Byung-Soo,Lim, Ho-Nam,Kwon, Il Keun 한국섬유공학회 2017 Fibers and polymers Vol.18 No.11
<P>Hydrogel-based integral nerve electrodes have been studied as an effective implant strategy for recovery after a spinal cord injury (SCI). However, a weak physical connection between the hydrogel and nerve electrode can lead to implant failure. In this study, we introduce poly(L-lactic acid) (PLA) nanorods (PLANRs) as a new approach to improve the physical property, i.e. stability of agarose hydrogel-based integrated neuro-electrodes. The hydrogels were characterized by scanning electron microscope (SEM), rheometry, and tensile test machine. Thus, the hydrogels containing PLANRs displayed high mechanical properties. These interesting findings suggest that PLANRs enhance the mechanical properties of integral nerve electrode hydrogels making them useful materials in neural tissue engineering.</P>
Heo, Min,Lee, Sang Jin,Heo, Dong Nyoung,Lee, Donghyun,Lim, Ho-Nam,Moon, Ji-Hoi,Kwon, Il Keun Elsevier 2018 APPLIED SURFACE SCIENCE - Vol.432 No.2
<P><B>Abstract</B></P> <P>Bone related-bacterial diseases including wound infections and osteomyelitis (OM) still remain a serious problem. In this study, a hybrid co-electrospun membrane consisting of gelatin (GE) and Poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactide-co-glycolide) (PLGA) fibrous sheets containing different concentrations (0, 0.1, 0.5, and 1wt%) of silver sulfadiazine (AgSD) was designed to provide for improved antimicrobial effect and biocompatibility. Well-defined products were characterized by physicochemical analyses. For biological <I>in vitro</I> assessments, mouse osteoblastic MC3T3-E1 cells were cultured on the scaffolds. This test was done in order to assay for cytotoxicity by measuring cell proliferation. Antibacterial activity against gram-negative <I>Pseudomonas aeruginosa</I> (<I>P. aeruginosa</I>), gram-positive <I>Staphylococcus aureus</I> (<I>S. aureus</I>), and Methicillin-resistant <I>Staphylococcus aureus</I> (MRSA) was also tested. These biological tests showed that GE/PLGA-AgSD scaffolds had good cell viability, as well as effective antimicrobial activity. These remarkable results suggest that GE/PLGA-AgSD scaffolds possess great potential for the treatment of OM and can find many uses in the field of bone tissue engineering.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The hybrid nanofiber was well-fabricated to different of two polymers using co-electrospun system. </LI> <LI> The presence of silver sulfadiazine and silver ion release from the co-electrospun nanofiber was clearly proved. </LI> <LI> The developed co-electrospun nanofiber showed not only excellent antibacterial effect, but also low cytotoxicity through <I>in vitro</I> tests. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Lee, Donghyun,Heo, Dong Nyoung,Lee, Sang Jin,Heo, Min,Kim, Jeongho,Choi, Samjin,Park, Hun-Kuk,Park, Young Guk,Lim, Ho-Nam,Kwon, Il Keun Elsevier 2018 APPLIED SURFACE SCIENCE - Vol.432 No.2
<P><B>Abstract</B></P> <P>Poly(lactide-co-glycolide) (PLGA) is a biocompatible and biodegradable polymer that has been widely used in devices for tissue engineering and drug delivery applications. Gold nanoparticles (GNPs) have also been used as biomaterials and have been found to have a positive effect on bone formation. In this study, we synthesized thiol end-capped PLGA (PLGA-SH) and used it for binding GNPs. This PLGA was processed into a sheet form via electrospinning. GNPs with an approximate size of 30nm were attached onto the PLGA-SH sheet surfaces (PLGA-GNPs). This membrane was characterized by thermogravimetric analysis, ultraviolet/visible spectrophotometry, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscopy. Characterization results show that the GNPs are well attached on the PLGA-SH sheet and it is possible to control the GNPs load. Additionally, in-vitro results showed that PLGA-GNPs have good biocompatibility. They were also found to enhance osteogenic differentiation of human adipose derived stem cells. From these results, we have determined that the PLGA-GNP fibers can be useful as materials for bone regeneration and can also potentially serve as drug carriers.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We designed and prepared a novel PLGA nanofibrous sheet for binding GNPs using a simple process. </LI> <LI> The objective this study was to design a process for manufacturing PLGA-GNPs nanofibrous sheets which can be applied to biomaterials. </LI> <LI> The biocompatibility and osteoinductive effect of PLGA-GNPs were demonstrated through in vitro test using a human adipose derived stem cells. </LI> <LI> The developed scaffolds may be suitable as bone cell proliferation substrates for use in bone tissue engineering applications. </LI> </UL> </P>