• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.673-697
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• 2018

BACKGROUND: Cartilage tissue engineering (CTE) aims to obtain a structure mimicking native cartilage tissue through the combination of relevant cells, three-dimensional scaffolds, and extraneous signals. Implantation of 'matured' constructs is thus expected to provide solution for treating large injury of articular cartilage. Type I collagen is widely used as scaffolds for CTE products undergoing clinical trial, owing to its ubiquitous biocompatibility and vast clinical approval. However, the long-term performance of pure type I collagen scaffolds would suffer from its limited chondrogenic capacity and inferior mechanical properties. This paper aims to provide insights necessary for advancing type I collagen scaffolds in the CTE applications. METHODS: Initially, the interactions of type I/II collagen with CTE-relevant cells [i.e., articular chondrocytes (ACs) and mesenchymal stem cells (MSCs)] are discussed. Next, the physical features and chemical composition of the scaffolds crucial to support chondrogenic activities of AC and MSC are highlighted. Attempts to optimize the collagen scaffolds by blending with natural/synthetic polymers are described. Hybrid strategy in which collagen and structural polymers are combined in non-blending manner is detailed. RESULTS: Type I collagen is sufficient to support cellular activities of ACs and MSCs; however it shows limited chondrogenic performance than type II collagen. Nonetheless, type I collagen is the clinically feasible option since type II collagen shows arthritogenic potency. Physical features of scaffolds such as internal structure, pore size, stiffness, etc. are shown to be crucial in influencing the differentiation fate and secreting extracellular matrixes from ACs and MSCs. Collagen can be blended with native or synthetic polymer to improve the mechanical and bioactivities of final composites. However, the versatility of blending strategy is limited due to denaturation of type I collagen at harsh processing condition. Hybrid strategy is successful in maximizing bioactivity of collagen scaffolds and mechanical robustness of structural polymer. CONCLUSION: Considering the previous improvements of physical and compositional properties of collagen scaffolds and recent manufacturing developments of structural polymer, it is concluded that hybrid strategy is a promising approach to advance further collagen-based scaffolds in CTE.

• Journal of Biomedical Engineering Research
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• v.38 no.5
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• pp.248-255
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• 2017

Polyurethane/polyethylene glycol(PU/PEG) hybrid scaffolds with various concentrations of PEG (0 to 50wt%) were prepared by electrospinning to evaluate the mechanical properties and the biocompatibility of the PU/PEG blend scaffolds. The 12wt% PU/PEG polymers were studied due to the absence of beads. The ultimate tensile strength of 12wt% PU was $8.2{\pm}0.5MPa$. The strength increased to $9.2{\pm}0.7MPa$ when 10% PEG was added to PU. However, the dry and the wet strength of PU/PEG scaffolds began to decrease dramatically when the PEG content was more than 10wt%. No cytotoxicity was observed for all the PU/PEG scaffolds investigated, indicating that the PU/PEG hybrid scaffolds are clinically safe and effective to small-diameter vascular grafts. In addition, the L-929 cells attached and proliferated well on the PU/PEG hybrid scaffolds.

• Proceedings of the Materials Research Society of Korea Conference
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• 2009.11a
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• pp.12.1-12.1
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• 2009

Nano-hydroxyapatite (N-HAp)has shown the pivotal role in producing bone-regenerative materials since it has similarity to natural bone minerals in terms of size, morphology, and the composition. Currently, the combination of biopolymers and N-HAp is recognizedas an attractive approach in generating hybrid scaffolds for bone tissueengineering. Surface engineering is an important issue since it determines whether cells can effectively adhere and proliferate on porous scaffolds. We aim to develop a synthetic approach to porous 3D scaffolds by immobilizing N-HAp on pore surfaces. The discrete nano-level anchoring of N-HAp on the scaffold pore surface is achieved using surface-repellent stable colloidal N-HAp with surface phosphate functionality. This rational surface engineering enables surface-anchored N-HAp to express its overall intrinsic bioactivity,since N-HAp is not phase-mixed with the polymers. The porous polymer scaffolds with surface-immobilized N-HAp provide more favorable environments thanconventional bulk phase-mixed polymer/N-HAp scaffolds in terms of cellular interaction and growth. In vitro biological evaluation using alkalinephosphatase activity assay supports that immobilized N-HAp on pore surfaces of polymer scaffolds contributed to the more enhanced in vitro osteogenicpotential. Besides, the scaffolds with surface-exposed N-HAp provide favorable environments for enhanced in vivo bone tissue growth, estimated by characteristic biomarkers of bone formation such as collagen. The results suggest that newly developed hybrid scaffolds with surface-immobilized N-HApmay serve as a useful 3D substrate with pore surfaces featuring excellent bonetissue-regenerative properties. Acknowledgement. This research was supported by a grant (code #: 2009K000430) from 'Center for Nanostructured Materials Technology' under '21st Century Frontier R&D Programs' of the Ministry of Education, Science and Technology, Korea.

• Journal of the Korean Society of Manufacturing Process Engineers
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• v.17 no.1
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• pp.108-115
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• 2018

In bone tissue engineering, polycaprolactone (PCL) is one of the most widely used biomaterials to manufacture scaffolds as a synthetic polymer with biodegradability and biocompatibility. The polymer deposition system (PDS) with four axis heads, which can dispense bio-polymers, has been used in scaffold fabrication for tissue engineering applications. A dual-head deposition technology of PDS is an effective technique to fabricate 3D scaffolds. The electrospinning technology has been widely used to fabricate porous and highly interconnected polymer fibers. Thus, PDS can fabricate nanofiber-combined hybrid scaffolds using fused deposition modeling (FDM) and electrospinning methods. This study aims to fabricate nanofiber-combined scaffolds with uniform nanofibers using PDS. The PCL nanofibers were fabricated and evaluated according to the fabrication process parameters. PCL nanofibers were successfully fabricated when the applied voltage, tip-to-collector distance, flow rate, and solution concentration were 5 kV, 1 cm, 0.1 ml/h, and 8 wt%, respectively. The cell proliferation was evaluated according to the electrospinning time. Scanning electron microscopy was used to acquire images of the cross-sectioned hybrid scaffolds. The cell proliferation test of the PCL and nanofiber-combined hybrid scaffolds was performed using a CCK-8 assay according to the electrospinning time. The result of in-vitro cell proliferation using osteosarcoma MG-63 cells shows that the hybrid scaffold has good potential for bone regeneration.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.38 no.8
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• pp.875-880
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• 2014

Recently, three-dimensional scaffolds and nanofibers are being developed for bone tissue regeneration. In this study, we fabricated a hybrid scaffold using a nano-micro precision deposition system. The fabrication process involved the application of the solid freeform fabrication (SFF) technology and electrospinning. The hybrid scaffolds were combined using micro scaffolds and nanofibers. The nanofibers were deposited on each layer of the micro scaffolding using the electrospinning process. The micro scaffolds were fabricated using the SFF technology at a temperature of $100^{\circ}C$, pressure of 650 kPa, and scan velocity of 250 mm/s. Nanofiber fabrication was conducted by means of electrospinning using the flow rate, solution concentration, distance from the tip to the collector (TCD), and voltage. The nanofibers were fabricated using a flow rate of 0.1 ml/min, voltage of 5 kV, TCD of 1 mm, and 10 wt% of solution concentration. MG-63 cells were seeded into the hybrid scaffold for the purpose of its evaluation.

• Journal of the Korean Ceramic Society
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• v.41 no.7
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• pp.497-502
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• 2004

A hybrid coextrusion and lamination process has been developed to fabricate macrochanneled bioceramic scaffolds. This process was mainly composed of three steps (i.e., coextrusion of thermoplastic compound, lamination, and thermal treatment), forming unique pore channels in dense bioceramic body. Pore channels were formed by removing carbon black material, while calcium phosphate or Tetragonal Zirconia Polycrystals (TZP) with a calcium phosphate coating layer were used as dense body. Two kinds of pore structures were fabricated; that is, the pore channels were formed in uni- or three-directional array. Such macrochanneled bioceramic scaffolds exhibited the precisely controlled pore structure (pore size, porosity, and interconnection), offering excellent mechanical properties and cellular responses.

• Macromolecular Research
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• v.15 no.5
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• pp.424-429
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• 2007

A procedure for the surface hydrolysis of an electrospun poly(${\epsilon}$-caprolactone) (PCL) fibrous scaffold was developed to enhance the adhesion and proliferation of osteoblasts. The surface hydrolysis of fibrous scaffolds was performed using NaOH treatment for the formation of carboxyl groups on the fiber surfaces. The hydrolysis process did not induce deformation of the fibers, and the fibers retained their diameter. The cell seeding density on the NaOH-treated PCL fibrous scaffolds was more pronounced than on the non-treated PCL fibers used as a control. The alkaline phosphatase activity, osteocalcin and a mineralization assay strongly supported that the surface-hydrolyzed PCL fibrous scaffolds provided more favorable environments for the proliferation and functions of osteoblasts compared to the non-treated PCL fibrous scaffolds use as a control.

• Journal of Biomedical Engineering Research
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• v.27 no.5
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• pp.224-228
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• 2006

The object of this study is to investigate the potential of dual-electrospun polymer based structure for vascular tissue engineering, especially for the medium or small sue blood vessels. Polyurethane(PU), which is known to be biocompatible in this area, was electrospun with poly(ethylene oxide) (PEO). Concentration of PU was fixed at 20wt%, while that of PEO was set from 15 to 35wt%. Morphological features were observed by SEM image and measurement of porosity and cellular responses were tested before and after extracting PEO from the hybrid scaffolds by immersing the scaffolds into distilled water. The diameter of PEO fibers were ranged from 200nm to 500nm. The lower concentration of PEO tended to show beads. The porosity of the scaffolds after extracting PEO was highly increased with higher concentration of PEO as expected. Also, higher proliferation rate of smooth muscle cells was observed at higher concentration of PEO than at the lower concentration and without PEO. As conclusions, this dual electrospinning technique combined with PU and PEO is expected to overcome the current barrier of cell penetration by providing more space for cells to proliferation.

• Macromolecular Research
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• v.10 no.3
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• pp.158-167
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• 2002

In order to endow with new bioactive functionality from small intestine submucosa (SIS) powder as natural source to poly (L-lactide) (PLA) and poly (lactide-co-glycolide) (PLGA) synthetic biodegradable polymer, porous SIS/PLA and SIS/PLGA as natural/synthetic composite scaffolds were prepared by means of the solvent casting/salt leaching methods for the possibility of the application of tissue engineered bone and cartilage. A uniform distribution of good interconnected pores from the surface to core region was observed the pore size of 40~500 ${\mu}{\textrm}{m}$ independent with SIS amount using the solvent casting/salt leaching method. Porosities, specific pore areas as well as pore size distribution also were almost same. After the fabrication of SIS/PLA hybrid scaffolds, the wetting properties was greatly enhanced resulting in more uniform cell seeding and distribution. Five groups as PGA non-woven mesh without glutaraldehyde (GA) treatment, PLA scaffold without or with GA treatment, and SIS/PLA (Code No.3 ; 1 : 12 of salt content, (0.4 : 1 of SIS content, and 144 ${\mu}{\textrm}{m}$ of median pore size) without or with GA treatment were implanted into the back of nude mouse to observe the effect of SIS on the induction of cells proliferation by hematoxylin and eosin, and von Kossa staining for 8 weeks. It was observed that the effect of SIS/PLA scaffolds with GA treatment on bone induction are stronger than PLA scaffolds, that is to say, in the order of PLA/SIS scaffolds with GA treatment > PLA/SIS scaffolds without GA treatment > PGA nonwoven > PLA scaffolds only with GA treatment = PLA scaffolds only without GA treatment for the osteoinduction activity. The possible explanations are (1) many kinds of secreted, circulating, and extracellular matrix-bound growth factors from SIS to significantly affect critical processes of tissue development and differentiation, (2) the exposure of SIS to GA resulted in significantly calcification, and (3) peri-implant fibrosis due to covalent bonding between collagen molecule by crosslinking reaction. In conclusion, it seems that SIS plays an important role for bone induction in SIS/PLA scaffolds for the application of tissue engineering area.

• Polymer(Korea)
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• v.34 no.5
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• pp.474-479
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• 2010

We developed laminated cylindrical scaffolds composed of poly(lactide-co-glycolide)(PLGA) and keratin, and investigated their potential for tissue engineering and disk regeneration. The scaffold was designed to have two parts, i.e. inner cylinder and outer disk, to mimic a natural disk. The outer disk was composed of PLGA and the inner cylinder was prepared using PLGA film or PLGA/keratin hybrid film. In this study, we investigated the effects of keratin on the growth and proliferation of annulus fibrous(AF) cells in the cylindrical scaffolds. Scaffolds containing PLGA/keratin films showed a significantly higher cell proliferation and expression of collagen I and II than the counterpart with PLGA films. Keratin containing scaffolds also exhibited an excellent mechanical strength, demonstrating that keratin influences the proliferation of annulus fibrous cells. The results provide valuable information on PLGA/keratin films for tissue engineered disk regeneration.