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Biomedical subjects

Il Keun Kwon

Publications and source records attributed to Il Keun Kwon.

12 recordsLinked to original sources

In situ visualization of paclitaxel distribution and release by coherent anti-Stokes Raman scattering microscopy.

Visualization of three-dimensional distribution of drug molecules and subsequent changes during the release process is critical for understanding drug delivery mechanisms as well as designing tailor-made release profiles. This study utilized coherent anti-Stokes Raman scattering (CARS) imaging to examine paclitaxel distribution in various polymer films with lateral resolution of 0.3 microm and depth resolution of 0.9 microm. Raman bands in the CH stretch vibration and fingerprint regions were used to distinguish paclitaxel from the polymers. The detection sensitivity was measured to be 29 mM by imaging paclitaxel molecules dissolved in N,N-dimethylformamide solution. Release of paclitaxel from a polymer matrix was monitored at an acquisition speed of 1 frame/s. Our results show that CARS microscopy can be used effectively for in situ imaging of native drug molecules in a delivery system.

Microscopy↗

Structural features and mechanical properties of in situ-bonded meshes of segmented polyurethane electrospun from mixed solvents.

The relationships between the structural features and mechanical properties of electrospun segmented polyurethane (SPU) meshes and electrospinning parameters such as formulation (e.g., polymer concentration and solvent mixing ratio) and operation parameters (e.g., applied voltage, air gap, and flow rate) were studied with the use of a mixed-solvent system of tetrahydrofuran (THF) and N,N-dimethylacrylamide (DMF). After the relationships between the structure of electrospun SPU and the operation parameters under a fixed SPU concentration of single THF solution were established, SPU was electrospun from the mixed solvent of THF and DMF with different mixing ratios [DMF content: 5, 10, and 30% (v/v)]. Scanning electron microscopy showed that an increase in DMF ratio significantly enhances the degree of bonding between SPU fibers at contact sites and decreases the diameter of fibers formed. The porosimetric characterization showed the following: (1) The porosity of the electrospun SPU meshes decreased with an increase of DMF ratio. (2) The pore size distribution exhibited three representative peaks of different void sizes (i.e., approximately 5, 20, and 70 microm). (3) The proportion of the 20-microm void markedly decreased with an increase in DMF ratio. A tensile test on the meshes showed that an increase in DMF ratio induces an increase in elasticity of the mesh. Such a regulation of the structural features and mechanical properties of electrospun SPU meshes using a mixed-solvent system with low- and high-boiling-point solvents may be useful in the engineering of SPU-fiber based matrices or scaffolds.

Acrylamides↗

Mechano-active scaffold design based on microporous poly(L-lactide-co-epsilon-caprolactone) for articular cartilage tissue engineering: dependence of porosity on compression force-applied mechanical behaviors.

An essential component of functional articular cartilage tissue engineering is a mechano-active scaffold, which responds to applied compression stress and causes little permanent deformation. As the first paper of a series on mechano-active scaffold-based cartilage tissue engineering, this study focused on mechanical responses to various modes of loading of compression forces and subsequent selection of mechano-active scaffolds from the biomechanical viewpoint. Scaffolds made of elastomeric microporous poly(L-lactide-co-epsilon-caprolactone) (PLCL) with open-cell structured pores (300 approximately 500 microm) and with different porosities ranging from 71 to 86% were used. The PLCL sponges and rabbit articular cartilage tissue were subjected to compression/unloading tests (0.1 and 0.005 Hz) at 5 kPa, and stress relaxation tests at 10, 30, and 50% strain. The measurements of the maximum strain under loading and residual strain under unloading for compression tests and the maximum stress and equilibrium stress in the stress relaxation test showed that the lower the porosity, the closer the mechanical properties are to those of native cartilage tissue. Among the PLCL sponges, the sponge with 71% porosity appears to be a suitable cartilage scaffold.

Animals↗

Novel bactericidal surface: Catechin-loaded surface-erodible polymer prevents biofilm formation.

We developed a novel bactericidal surface based on a catechin-loaded surface-erodible polymer. (-)-Epigallocatechin-3-gallate (EGCg), which is the main constituent of tea catechins, showed a dose-dependent inhibitory effect on Escherichia coli biofilm formation and a dose-dependent enhanced destructive effect on biofilm. EGCg-immobilized surfaces were prepared by photopolymerization of liquid biodegradable polyesters. The releasing rate was enhanced with an increase in surface-erosion rate of photocured polymers. Polymers with high releasing capacity dose-dependently reduced biofilm formation on the surfaces. The confocal laser scanning microscopic and scanning electron microscopic observations revealed that EGCg induced biofilm-destructing activities, which include bacterial membrane damage, degradation of exopolysaccharides, and detachment of colonized cells. From these results, potential advantages of the clinical use of catechin-loaded polymer-coated implants or catheters are discussed in terms of a reduced occurrence of biomaterial-centered infections without substantial toxicity or adverse effects.

Anti-Infective Agents↗

Mechanical responses of a compliant electrospun poly(L-lactide-co-epsilon-caprolactone) small-diameter vascular graft.

To design a "mechano-active" small-diameter artificial vascular graft, a tubular scaffold made of elastomeric poly(L-lactide-co-epsilon-caprolactone) fabrics at different wall thicknesses was fabricated using an electrospinning (ELSP) technique. The wall thickness of the fabricated tube (inner diameter; approximately 2.3-2.5 mm and wall thickness; 50-340 microm) increased proportionally with ELSP time. The wall thickness dependence of mechanical responses including intraluminal pressure-induced inflation was determined under static and dynamic flow conditions. From the compliance-related parameters (stiffness parameter and diameter compliance) measured under static condition, the smaller the wall thickness, the more compliant the tube. Under dynamic flow condition (1 Hz, maximal/minimal pressure of 90 mmHg/45 mmHg) produced by a custom-designed arterial circulatory system, strain, defined as the relative increase in diameter per pulse, increased with the decrease in wall thickness, which approached that of a native artery. Thus, a mechano-active scaffold that pulsates synchronously by responding to pulsatile flow was prepared using elastomeric PLCL as a base material and an ELSP technique.

Animals↗

Photo-iniferter-based thermoresponsive block copolymers composed of poly(ethylene glycol) and poly(N-isopropylacrylamide) and chondrocyte immobilization.

A series of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM)-poly(ethylene glycol) (PEG) block copolymers with various PNIPAM contents and copolymer architectures, such as linear, four-armed and eight-armed configurations, were prepared by iniferter-based photopolymerization of dithiocarbamylated PEGs (DC-PEGs) under ultraviolet (UV)-light irradiation. The increase in monomer/DC-PEG feed ratio resulted in an increase in both the molecular weight and PNIPAM content of copolymers. The measurement of the optical transmittances of aqueous solutions of PNIPAM-PEG block copolymers determined the lower critical solution temperatures (LCSTs) of block copolymers, which ranged from 31.3 to 34.0 degrees C. LCST decreased with increasing block length of PNIPAM and with the formation of a branched architecture. Rabbit chondrocytes were immobilized and cultured in a three-dimensional (3D) gel composed of PNIPAM-PEG block copolymer at 37 degrees C. Gels prepared from copolymers with higher PNIPAM contents at higher concentrations appeared to exhibit a minimal decrease in both cell number and cell viability during a 7-day culture. Cell viability dependencies on material and formulation parameters and the potential use of PNIPAM-PEG block copolymers as an in situ formable scaffold for an engineered cartilage tissue were discussed.

Acrylic Resins↗

Mechano-active scaffold design of small-diameter artificial graft made of electrospun segmented polyurethane fabrics.

To fabricate a "mechano-active" tubular scaffold of nonwoven mesh-type small-diameter artificial graft made of the synthetic durable elastomer, segmented polyurethane, the fabrication technique of electrospinning on a mandrel under a high rotation speed and transverse movement was used. Emphasis was placed on how the rotation speed of the mandrel and the fusion or welding states of fibers at contact points affect the compliance (ease of intraluminal pressure-dependent circumferential inflation) and Young's modulus determined by uniaxial stretching in the longitudinal and circumferential directions. The results showed that a high rotation speed is attributed to exhibit isotropic mechanical properties in the entire range of applied strain but reduces the compliance, and a high fusion state, which is produced using a mixed solvent with a high content of high-boiling-point solvent, reduces the compliance but is expected to exhibit high durability in a continuously loaded pulsatile stress field in an arterial circulatory system.

Artificial Organs↗

Photo-polymerized microarchitectural constructs prepared by microstereolithography (muSL) using liquid acrylate-end-capped trimethylene carbonate-based prepolymers.

Precision microarchitectural constructs made of acrylated trimethylene carbonate (TMC)-based liquid prepolymers were photo-polymerized using a custom-designed microstereolithographic apparatus. In this study, three different photo-polymerizable liquid prepolymers were prepared by the polymerization of TMC with a low molecular weight poly(ethylene glycol) (PEG) (mol. wt. 200 or 1000); designated as PEG200 or PEG1000, respectively or trimethylolpropane (TMP) as an initiator, and subsequently end-capped with an acrylate group. As a result of layer-by-layer photo-irradiation of the prepolymer with a movable ultraviolet light pen driven by computer-aided design, a three-dimensional (3D) micropillar array, a microbank array, a microcone array, and multi-microtunnels formed on a platform plate or a glass plate were precisely fabricated. The PEG-based polymers exhibited a very low cell adhesion potential, whereas the TMP-based hydrophobic polymer exhibited high cell adhesion and proliferation potentials. The microbank array, which consisted of a plate made of the TMP-based polymer and microbanks made of the PEG200-based polymer, caused cell adhesion and proliferation only on the plate. Upon the implantation of microcone arrays under the subcutis of rats, the photo-polymerized construct made of the poorly swellable PEG200-based polymer exhibited only surface erosion and limited drug loading and releasing potentials. On the other hand, the photo-polymerized construct made of the highly swellable PEG1000-based polymer exhibited not only surface erosion but also bulk erosion and high drug loading and releasing potentials. In this paper, we discuss their potential biomedical applications.

3T3 Cells↗

Electrospun nano- to microfiber fabrics made of biodegradable copolyesters: structural characteristics, mechanical properties and cell adhesion potential.

Nano- to micro-structured biodegradable poly(L-lactide-co-epsilon-caprolactone) (PLCL) fabrics were prepared by electrospinning. Electrospun microfiber fabrics with different compositions of PLCL (mol% in feed; 70/30, 50/50, and 30/70), poly(L-lactide) (PLL) and poly(epsilon-caprolactone) (PCL) were obtained using methylene chloride (MC) as a solvent. The PLL microfiber exhibited a nanoscale-pore structure with a pore diameter of approximately 200-800 nm at the surface and subsurface regions, whereas such a surface structure was hardly observed in other polymers containing CL. The microfiber fabric made of PLCL 50/50 was elastomeric. Nanoscale-fiber fabrics with PLCL 50/50 (approx. 0.3 or 1.2 microm in diameter) were electrospun using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent. Mercury porosimetry showed that the decrease in the fiber diameter of the fabric decreased porosity, but increased fiber density and mechanical strength. Human umbilical vein endothelial cells (HUVECs) were adhered well and proliferated on the small-diameter-fiber fabrics (0.3 and 1.2 microm in diameter), both of which are dense fabrics, whereas markedly reduced cell adhesion, restricted cell spreading and no signs of proliferation were observed on the large-diameter-fiber fabric (7.0 microm in diameter). The potential biomedical application of electrospun PLCL 50/50 was discussed.

Absorbable Implants↗

Elastic biodegradable poly(glycolide-co-caprolactone) scaffold for tissue engineering.

Cyclic mechanical strain has been demonstrated to enhance the development and function of engineered smooth muscle (SM) tissues, and it would be necessary for the development of the elastic scaffolds if one wishes to engineer SM tissues under cyclic mechanical loading. This study reports on the development of an elastic scaffold fabricated from a biodegradable polymer. Biodegradable poly(glycolide-co-caprolactone) (PGCL) copolymer was synthesized from glycolide and epsilon-caprolactone in the presence of stannous octoate as catalyst. The copolymer was characterized by (1)H-NMR, gel permeation chromatography and differential scanning calorimetry. Scaffolds for tissue engineering applications were fabricated from PGCL copolymer using the solvent-casting and particle-leaching technique. The PGCL scaffolds produced in this fashion had open pore structures (average pore size = 250 microm) without the usual nonporous skin layer on external surfaces. Mechanical testing revealed that PGCL scaffolds were far more elastic than poly(lactic-co-glycolic acid) (PLGA) scaffolds fabricated using the same method. Tensile mechanical tests indicated that PGCL scaffolds could withstand an extension of 250% without cracking, which was much higher than withstood by PLGA scaffolds (10-15%). In addition, PGCL scaffolds achieved recoveries exceeding 96% at applied extensions of up to 230%, whereas PLGA scaffolds failed (cracked) at an applied strain of 20%. Dynamic mechanical tests showed that the permanent deformation of the PGCL scaffolds in a dry condition produced was less than 4% of the applied strain, when an elongation of 20% at a frequency of 1 Hz (1 cycle per second) was applied for 6 days. Moreover, PGCL scaffolds in a buffer solution also had permanent deformations less than 5% of the applied strain when an elongation of 10% at a frequency of 1 Hz was applied for 2 days. The usefulness of the PGCL scaffolds was demonstrated by engineering SM tissues in vivo. This study shows that the elastic PGCL scaffolds produced in this study could be used to engineer SM-containing tissues (e.g. blood vessels and bladders) in mechanically dynamic environments.

Absorbable Implants↗

Photocurable biodegradable liquid copolymers: synthesis of acrylate-end-capped trimethylene carbonate-based prepolymers, photocuring, and hydrolysis.

Various photocurable liquid biodegradable trimethylene carbonate (TMC)-based (co)oligomers were prepared by ring-opening (co)polymerization of TMC with or without L-lactide (LL) using low molecular weight poly(ethylene glycol) (PEG) (mol wt 200, 600, or 1000) or trimethylolpropane (TMP) as an initiator. Resultant (co)oligomers were pastes, viscous liquids, or liquids at room temperature, depending on the monomer composition and monomer/initiator ratio. Liquid (co)oligomers were subsequently end-capped with acrylate groups. Upon visible-light irradiation in the presence of camphorquinone as a radical generator, rapid liquid-to-solid transformation occurred to produce photocured solid. The photocuring yield increased with photoirradiation time, photointensity, and camphorquinone concentration. The photocured polymers derived from low molecular weight PEG (PEG200) and TMP exhibited much reduced hydrolysis potential compared with PEG1000-derived polymers in terms of weight loss, water uptake, and swelling depth. Force-distance curve measurements by nanoindentation using atomic force microscopy clearly showed that Young's moduli of the photocured polymer films decreased with increasing hydrolysis time. Their potential biomedical applications are discussed.

Acrylates↗

Co-electrospun nanofiber fabrics of poly(L-lactide-co-epsilon-caprolactone) with type I collagen or heparin.

Functionally designed elastomeric nanofiber fabrics made of the equimolar copolyester, poly(L-lactide-co-epsilon-caprolactone) (PLCL), with type I collagen or the tri-n-butylamine salt of heparin (heparin-TBA) were co-electrospun using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent. The co-electrospun fabrics (mixing ratio: 0, 5, 10, 30, 50, 70, and 100 wt % of collagen to PLCL) consisted of nanoscale fibers with a mean diameter ranging from approximately 120 to 520 nm. An increase in collagen content in the solution resulted in a decrease in the mean diameter of fibers. Transmission electron microscopy (TEM) showed that collagen in a co-electrospun fiber was phase-separated to form a dispersed phase, which was localized in the interior and peripheral region in the continuous matrix phase of fibers. The tensile strength was decreased with increasing collagen content. Human umbilical vein endothelial cells (HUVECs) were highly elongated and well spread on the fibrous surfaces of fabrics made of PLCL with 5 wt % or 10 wt % collagen. Heparin-TBA (mixing ratio: 1, 5, and 10 wt % to PLCL), soluble in HFIP, was co-electrospun with PLCL to form a fabric. TEM observation showed that heparin-TBA formed as a dispersed phase in a PLCL nanofiber. The releasing rate, released amount, and surface content of heparin-TBA were increased with increasing heparin-TBA content in co-electrospun fabrics. The potential biomedical application of co-electrospun PLCL with type I collagen or heparin-TBA was discussed.

Cells, Cultured↗