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Seoul, South Korea

Bhang S.H.,Seoul National University | Jung M.J.,Hanyang University | Shin J.-Y.,Seoul National University | La W.-G.,Seoul National University | And 5 more authors.
Biomaterials | Year: 2013

While subcutaneous tissue has been proposed as a potential site for pancreatic islet transplantation, concern remains that the microvasculature of subcutaneous tissue is too poor to support transplanted islets. In an effort to overcome this limitation, we evaluated whether fibrin gel with human adipose-derived stem cells (hADSCs) and rat pancreatic islets could cure diabetes mellitus when transplanted into the subcutaneous space of diabetic mice. Subcutaneously co-transplanted islets and hADSCs showed normalization of the diabetic recipient's blood glucose levels. The result was enhanced by co-treatment of fibroblast growth factor-2 (FGF2) in the fibrin gel. The hADSCs enhanced islet viability after transplantation by secreting various growth factors that can protect islets from hypoxic damage. Afterward, hADSCs could maintain islet viability by recruiting new microvasculature nearby the transplanted islets via overexpression of vascular endothelial growth factor (VEGF). The hADSCs did not directly differentiate into endothelial cells (no detection of biomarkers of human endothelial cells), but showed evidence of differentiation toward insulin-secreting cells (detection of human insulin). Mice receiving islet transplantation alone did not become normoglycemic. Collectively, co-transplantation of fibrin gel with islets and hADSCs will expand the indications for islet transplant therapy and the potential clinical application of cell-based therapy. © 2013 Elsevier Ltd.

Park S.,Seoul National University | Bhang S.H.,Seoul National University | La W.-G.,Seoul National University | Seo J.,Seoul National University | And 3 more authors.
Biomaterials | Year: 2012

We developed hyaluronic acid (HA)-based multilayer films capturing polymeric nanocarriers (NCs) for drug delivery. The electrostatic interactions between positively charged linear polyethylene imines (LPEI) and negatively charged HAs are the main driving forces to form multilayers based on the layer-by-layer (LbL) deposition. NCs were easily incorporated within the multilayer film due to intra- and/or inter-hydrogen bonding among HA chains. The amount of NCs captured by the HA chains was varied by the ratio between HAs and NCs as well as the length (i.e., molecular weight) and absolute number density of HAs in solution. Biocompatibility of the NC-capturing HA multilayer films was tested with the human dermal fibroblast (HDF) culture. In addition, the controlled release of paclitaxel (PTX) from the HA multilayer films successfully led to the apoptosis of human aortic smooth muscle cells (hSMC) in vitro, implying that the NC-capturing HA multilayer films would be quite useful as drug-eluting stent systems to prevent the restenosis after surgery. © 2012 Elsevier Ltd.

Park S.,Seoul National University | Park J.,Seoul National University | Jo I.,Seoul National University | Cho S.-P.,Seoul National University | And 9 more authors.
Biomaterials | Year: 2015

Carbon nanotubes (CNTs) have shown great potential in biomedical fields. However, invivo applications of CNTs for regenerative medicine have been hampered by difficulties associated with the fabrication of three-dimensional (3D) scaffolds of CNTs due to CNTs' nano-scale nature. In this study, we devised a new method for biosynthesis of CNT-based 3D scaffold by in situ hybridizing CNTs with bacterial cellulose (BC), which has a structure ideal for tissue-engineering scaffolds. This was achieved simply by culturing Gluconacetobacter xylinus, BC-synthesizing bacteria, in medium containing CNTs. However, pristine CNTs aggregated in medium, which hampers homogeneous hybridization of CNTs with BC scaffolds, and the binding energy between hydrophobic pristine CNTs and hydrophilic BC was too small for the hybridization to occur. To overcome these problems, an amphiphilic comb-like polymer (APCLP) was adsorbed on CNTs. Unlike CNT-coated BC scaffolds (CNT-BC-Imm) formed by immersing 3D BC scaffolds in CNT solution, the APCLP-adsorbed CNT-BC hybrid scaffold (CNT-BC-Syn) showed homogeneously distributed CNTs throughout the 3D microporous structure of BC. Importantly, in contrast to CNT-BC-Imm scaffolds, CNT-BC-Syn scaffolds showed excellent osteoconductivity and osteoinductivity that led to high bone regeneration efficacy. This strategy may open a new avenue for development of 3D biofunctional scaffolds for regenerative medicine. © 2015 Elsevier Ltd.

Bhang S.H.,Sungkyunkwan University | Han J.,Seoul National University | Jang H.-K.,Seoul National University | Noh M.-K.,Seoul National University | And 7 more authors.
Biomaterials | Year: 2015

At high concentrations, manganese (Mn) promotes cellular neurodevelopment but causes toxicity. Here, we report that Mn ion at high concentrations can be delivered to pheochromocytoma 12 (PC12) cells using gold nanoparticles (AuNPs) to enhance cellular neurodevelopment without toxicity. Mn2+ release from AuNPs was designed to be pH-responsive so that low pH condition of the cell endosomes can trigger in situ release of Mn2+ from AuNPs after cellular uptake of Mn-incorporated AuNPs (MnAuNPs). Due to the differences in reduction potentials of Mn and Au, only Mn ionized and released while Au remained intact when MnAuNPs were uptaken by cells. Compared to PC12 cells treated with a high concentration of free Mn2+, PC12 cells treated with an equal concentration of MnAuNPs resulted in significantly enhanced cellular neurodevelopment with decreased apoptosis and necrosis. Treatment with a high concentration of free Mn2+ led to an abrupt consumption of a large amount of ATP for the intracellular transport of Mn2+ through the ion channel of the cell membrane and to mitochondrial damage caused by the high intracellular concentration of Mn2+, both of which resulted in cell necrosis and apoptosis. In contrast, MnAuNP-treated cells consumed much smaller amount of ATP for the intracellular transport of MnAuNPs by endocytosis and showed pH-triggered in situ release of Mn2+ from the MnAuNPs in the endosomes of the cells, both of which prevented the cell death caused by ATP depletion and mitochondrial damage. To our knowledge, this is the first report on the use of AuNPs as a vehicle for pH-responsive, intracellular delivery of metal ion, which may open a new window for drug delivery and clinical therapy. © 2015 Elsevier Ltd.

Bhang S.H.,Seoul National University | Kwon S.-H.,Seoul National University | Lee S.,Seoul National University | Kim G.C.,Kyung Hee University | And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Since pheochromocytoma 12 (PC12) cells have the ability of neuronal differentiation upon nerve growth factor (NGF) treatment, they are a good model for studying the neuronal differentiation. Establishing a strong adhesion of PC12 cells to the culture substrate may increase neuronal differentiation, and the use of L-3,4-dihydroxyphenylalanine (L-DOPA), which is responsible for the adhesive property of mussel adhesive proteins (MAPs), is a feasible strategy for such strong adhesion. We hypothesized that a polydopamine-modified surface can promote PC12 cell adhesion and subsequent neuronal differentiation. We examined whether polydopamine-modified surface promotes PC12 cell adhesion, and further evaluated the neuronal differentiation of these cells. The polydopamine modification enhanced the cell adhesion and viability, and also promoted the neuronal differentiation of NGF-stimulated PC12 cells, as evidenced by the elongation of neurites and expression of neuronal differentiation markers, by increasing the activation of NGF/Trk-Rho GTPase signal pathway. Our findings will help develop an improved strategy for functionalizing biomaterial substrates for less-adhesive cells including neural cells. © 2012 Elsevier Inc.

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