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Biomedical subjects

Hae-Won Kim

Publications and source records attributed to Hae-Won Kim.

At least 19 recordsLinked to original sources

Bioactive glass nanofiber-collagen nanocomposite as a novel bone regeneration matrix.

Nanoscale organized organic-inorganic nanocomposite systems have great potential in the development of biomaterials with advanced properties. Herein, we developed a novel nanocomposite biomaterial consisting of bioactive glass nanofiber (BGNF) and collagen reconstituted fibrous matrix for bone regenerative medicine. A sol-gel derived glass with a bioactive composition (58SiO(2). 38CaO.4P(2)O(5)) was electrospun to a nanoscale fiber with an average diameter of approximately 320 nm. The BGNF was subsequently hybridized with type I collagen, which is the main organic constituent of bone matrix. The BGNF and self-assembled collagen sol were combined in aqueous solution, and then crosslinked to produce a BGNF-collagen nanocomposite, in the form of either a thin membrane or a macroporous scaffold, by adopting appropriate processing conditions. The BGNF was observed to be distributed uniformly within the collagen reconstituted nanofibrous matrix. The nanocomposite matrices induced rapid formation of bone-like apatite minerals on their surfaces when incubated in a simulated body fluid, exhibiting excellent bioactivity in vitro. Osteoblastic cells showed favorable growth on the BGNF-collagen nanocomposite. In particular, the alkaline phosphatase activity of the cells on the nanocomposite was significantly higher than that on the collagen. This novel BGNF-collagen nanocomposite is believed to have significant potential in bone regeneration and tissue engineering applications.

Biocompatible Materials↗

Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly(lactic acid) for bone regeneration.

Development of fibrous matrices of bioceramic-biopolymer nanocomposite offers great potential in the field of bone regeneration and tissue engineering. However, in order to produce electrospun fibers with homogeneous structure, it is essential for the ceramic powder to be fine and to remain stable in suspension. Herein, we developed a novel method whereby the bioceramic hydroxyapatite (HA) was kept in suspension in biopolymer poly(lactic acid) (PLA). The strategy was to introduce a surfactant hydroxysteric acid (HSA) between the hydrophilic HA powder and the hydrophobic chloroform-dissolved PLA. The HA nanopowder was dispersed effectively in HSA and mixed homogeneously with PLA. Continuous and uniform fibers were generated successfully with diameters of approximately 1-2 microm, and featured a well-developed nanocomposite structure of HA nanopowder-dispersed PLA. Initial cellular assays showed excellent cell attachment and proliferation and also enhanced expression of alkaline phosphatase at 7 days of culturing. The HA-PLA nanocomposite fibers may be potentially useful in tissue engineering applications, particularly as three-dimensional substrates for bone growth.

Bone Regeneration↗

Initial responses of human osteoblasts to sol-gel modified titanium with hydroxyapatite and titania composition.

Sol-gel thin films of hydroxyapatite (HA) and titania (TiO(2)) have received a great deal of attention in the area of bioactive surface modification of titanium (Ti) implants. Sol-gel coatings were developed on Ti substrates of pure HA and TiO(2) and two composite forms, HA+10% TiO(2) and HA+20% TiO(2), and the biological properties of the coatings were evaluated. All the coating layers exhibited thin and homogeneous structures and phase-pure compositions (either HA or TiO(2)). Primary human osteoblast cells showed good attachment, spreading and proliferation on all the sol-gel coated surfaces, with enhanced cell numbers on all the coated surfaces relative to uncoated Ti control at day 1, as observed by MTT assay and scanning electron microscopy. Cell attachment rates were also enhanced on the pure HA coating relative to control Ti. The pure HA and HA+10% TiO(2) composite coating furthermore enhanced proliferation of osteoblasts at 4 days. Moreover, the gene expression level of several osteogenic markers including bone sialoprotein and osteopontin, as measured by RT-PCR at 24h, was shown to vary according to coating composition. These findings suggest that human primary bone cells show marked and rapid early functional changes in response to HA and TiO(2) sol-gel coatings on Ti.

Cell Proliferation↗

Nanofiber generation of hydroxyapatite and fluor-hydroxyapatite bioceramics.

In this study, we produced hydroxyapatite (HA) and fluor-hydroxyapatite (FHA) bioceramics as a novel geometrical form, the nanoscale fiber, for the biomedical applications. Based on the sol-gel precursors of the apatites, an electrospinning technique was introduced to generate nanoscale fibers. The diameter of the fibers was exploited in the range of a few micrometers to hundreds of nanometers (1.55 microm-240 nm) by means of adjusting the concentration of the sols. Through the fluoridation of apatite, the solubility of the fiber was tailored and the fluorine ions were well released from the FHA. The HA and FHA nanofibers produced in this study are considered to find potential applications in the biomaterials and tissue engineering fields.

Biocompatible Materials↗

Hydroxyapatite (HA) bone scaffolds with controlled macrochannel pores.

Hydroxyapatite (HA) macrochanneled porous scaffolds, with a controlled pore structure, were fabricated via a combination of the extrusion and lamination processes. The scaffold was architectured by aligning and laminating the extruded HA and carbon filaments. The macrochannel pores were formed by removing the carbon filaments after thermal treatments (binder removal and sintering). The porosity of the scaffolds was varied between 48 and 73% with a controlled pore size of approximately 450 microm, by adjusting the fractions of HA and carbon filaments. As the porosity was increased from 48 to 73%, the compressive strength decreased from 11.5 to 3.2 MPa. However, the osteoblast-like cell responses on the scaffold, such as the proliferation rate and alkaline phosphatase (ALP) activity, were significantly enhanced as the porosity was increased.

Alkaline Phosphatase↗

Nanofiber of ultra-structured aluminum and zirconium oxide hybrid.

An internally ultrastructured Al- and Zr-oxide hybrid was developed into a nanofiber. As a precursor for the generation of nanofiber, a hybridized sol was prepared using the Pechini-type sol-gel process, whereby the Al- and Zr-metallic ions were to be efficiently distributed and stabilized within the polymeric network. The hybridized sol was subsequently electrospun and heat treated to a nanofiber with diameters of tens to hundreds of nanometers. The internal structure of the nanofiber was organized at the molecular level, with the Al- and Zr-oxide regions being interspaced at distances of less than ten nanometers. This ultrastructured Al- and Zr-oxide hybrid nanofiber is considered to be potentially applicable in numerous fields.

Aluminum Oxide↗

Hydroxyapatite-TiO2 hybrid coating on Ti implants.

A hydroxyapatite (HA)-titania (TiO(2)) hybrid coating is developed to improve the biocompatibility of titanium (Ti) implants. The HA predeposited layer on Ti via electron beam (e-beam) evaporation is subsequently treated by micro-arc oxidation (MAO) to produce an HA-TiO(2) hybrid layer on Ti. The e-beam-deposited HA layer has a thickness of approximately 1 microm and was highly dense prior to MAO. By means of MAO treatment, a rough and porous TiO(2) layer is formed beneath the HA layer with a simultaneous local dissolution of the HA layer. Due to the HA precoating, high concentrations of Ca and P are preserved on the coating surface. The osteoblast-like cells on the hybrid coating layer grow and spread favorably. The cell proliferation rate on the hybrid coatings is not much different from that on pure Ti or simple MAO-treated Ti. However, the alkaline phosphatase (ALP) activity of the cells is significantly higher (p < 0.05) on the HA-TiO(2) hybrid coatings than on either the pure Ti or the simple MAO-treated specimen, suggesting that the cellular activity on the hybrid coatings is improved.

Cell Line↗

Fibrillar assembly and stability of collagen coating on titanium for improved osteoblast responses.

Collagen, as a major constituent of human connective tissues, has been regarded as one of the most important biomaterials. As a coating moiety on Ti hard-tissue implants, the collagen has recently attracted a great deal of attention. This article reports the effects of fibrillar assembly and crosslinking of collagen on its chemical stability and the subsequent osteoblastic responses. The fibrillar self-assembly of collagen was carried out by incubating acid-dissolved collagen in an ionic-buffered medium at 37 degrees C. The degree of assembly was varied with the incubation time and monitored by the turbidity change. The differently assembled collagen was coated on the Ti and crosslinked with a carbodiimide derivative. The partially assembled collagen contained fibrils with varying diameters as well as nonfibrillar aggregates. On the other hand, the fully assembled collagen showed the complete formation of fibrils with uniform diameters of approximately 100-200 nm with periodic stain patterns within the fibrils, which are typical of native collagen fibers. Through this fibrillar assembly, the collagen coating had significantly improved chemical stability in both the saline and collagenase media. The subsequent crosslinking step also improved the stability of the collagen coating, particularly in the unassembled collagen. The fibrillar assembly and the crosslinking of collagen significantly influenced the osteoblastic cell responses. Without the assembly, the collagen layer on Ti adversely affected the cell attachment and proliferation. However, those cellular responses were improved significantly when the collagen was assembled to fibrils and the assembly degree was increased. After crosslinking the collagen coating, these cellular responses were significantly enhanced in the case of the unassembled collagen but were not altered much in the assembled collagen. Based on these observations, it is suggested that the fibrillar assembly and the crosslinking of collagen require careful considerations in the collagen administration as a coating moiety.

Cell Line↗

On the feasibility of phosphate glass and hydroxyapatite engineered coating on titanium.

In this report, bioactive calcium phosphate (CaP) coatings were produced on titanium (Ti) by using phosphate-based glass (P-glass) and hydroxyapatite (HA), and their feasibility for hard tissue applications was addressed in vitro. P-glass and HA composite slurries were coated on Ti under mild heat treatment conditions to form a porous thick layer, and then the micropores were filled in with an HA sol-gel precursor to produce a dense layer. The resultant coating product was composed of HA and calcium phosphate glass ceramics, such as tricalcium phosphate (TCP) and calcium pyrophosphate (CPP). The coating layer had a thickness of approximately 30-40 microm and adhered to the Ti substrate tightly. The adhesion strength of the coating layer on Ti was as high as 30-33 MPa. The human osteoblastic cells cultured on the coatings produced by the combined method attached and proliferated favorably. Moreover, the cells on the coatings expressed significantly higher alkaline phosphatase activity than those on pure Ti, suggesting the stimulation of the osteoblastic activity on the coatings. On the basis of these observations, the engineered CaP coating layer is considered to be potentially applicable as a hard tissue-coating system on Ti-based implants.

Durapatite↗

Sol-gel-modified titanium with hydroxyapatite thin films and effect on osteoblast-like cell responses.

Titanium (Ti) surface was coated with hydroxyapatite (HA) films via the sol-gel method. The coating properties, such as crystallinity and surface roughness, were controlled and their effects on the osteoblast-like cell responses were investigated. The film crystallinity was controlled with different heat treatment temperatures (400, 500, and 600 degrees C): Also the surface roughness was changed by using different heating rates (1 and 50 degrees C/min). The obtained sol-gel films had a dense and homogeneous structure with a thickness about 1 mum. The film heat-treated at higher temperature had enhanced crystallinity (600>500>>400 degrees C), while retaining similar surface roughness. When heat-treated rapidly (50 degrees C/min), the film became quite rough, with roughness parameters being much higher (4-6 times) than that obtained at a low heating rate (1 degrees C/min). The dissolution rate of the film decreased with increasing crystallinity (400>>500>600 degrees C), and the rougher film had slightly higher dissolution rate. The attachment, proliferation, and differentiation behaviors of human osteosarcoma HOS TE85 cells were affected by the properties of the films. On the films with higher crystallinity (heat treated over 500 degrees C), the cells attached and proliferated well and expressed alkaline phosphatase (ALP) and osteocalcin (OC) to a higher degree as compared to the poorly crystallized film (heat treated at 400 degrees C). On the rough film, the cell attachment was enhanced, but the ALP and OC expression levels were similar as compared to the smooth films.

Cell Line↗

Biocompatibility of titanium implants modified by microarc oxidation and hydroxyapatite coating.

A thin hydroxyapatite (HA) layer was coated on a microarc oxidized titanium (MAO-Ti) substrate by means of the sol-gel method. The microarc oxidation (anodizing) enhanced the biocompatibility of the Ti, and the bioactivity was improved further by the sol-gel HA coating on the anodized Ti. The HA sol was aged fully to obtain a stable and phase-pure HA, and the sol concentration was varied to alter the coating thickness. Through the sol-gel HA coating, the Ca and P concentrations in the coating layer increased significantly. However, the porous morphology and roughness of the MAO-Ti was altered very little by the sol-gel treatment. The proliferation and alkaline phosphatase (ALP) activity of the osteoblast-like cells on the MAO/HA sol-gel-treated Ti were significantly higher than those on the MAO-Ti without the HA sol-gel treatment.

Absorbable Implants↗

Mechanical performance and osteoblast-like cell responses of fluorine-substituted hydroxyapatite and zirconia dense composite.

A fluorine-substituted hydroxyapatite (FHA) and zirconia (ZrO(2)) dense composite (50:50 by volume) was fabricated, and its feasibility for hard tissue applications was investigated in terms of its mechanical properties and osteoblast-like cell (MG63) responses in vitro. The incorporation of fluorine into the hydroxyapatite (HA) structure was highly effective in producing a completely dense apatite-ZrO(2) composite through a pressureless sintering route, by preventing the thermal degradation of the apatite and ZrO(2). The resultant FHA-ZrO(2) dense composite had excellent mechanical properties, such as flexural strength (310 MPa), fracture toughness (3.4 MPam(1/2)), hardness (10 GPa), and elastic modulus (160 GPa). The flexural strength and fracture toughness of the composite showed a noticeable improvement by a factor of approximately 4 with respect to the pure apatites (HA and FHA). The MG63 cellular responses to the composite were assessed in terms of the cell proliferation (cell number and [(3)H]-thymidine incorporation) and differentiation (alkaline phosphatase activity, osteocalcin, and collagen production). The cells on the FHA-ZrO(2) composite spread and grew well, and proliferated actively during the culture period. The expression of alkaline phosphatase, osteocalcin, and collagen by the cells on the composite showed a similar trend to that on the pure apatites, although slight down-regulations were observed, implying that the FHA-ZrO(2) 50:50 composite retains the osteoblastic functionality and traits of the pure HA ceramics to a high degree. This finding, in conjunction with the considerable improvements in mechanical properties, supports the extended use of this composite for hard tissue applications.

Biocompatible Materials↗

Hydroxyapatite and gelatin composite foams processed via novel freeze-drying and crosslinking for use as temporary hard tissue scaffolds.

Hydroxyapatite (HA) and gelatin composites were fabricated in a foam type via a novel freeze-drying and crosslinking technique. The morphological and mechanical properties of and in vitro cellular responses to the foams were investigated. The HA powder was added at up to 30 wt % into the gelatin solution, and the mixtures were freeze-dried and further crosslinked. The pure gelatin foam had a well-developed pore configuration with porosity and pore size of approximately 90% and 400-500 microm, respectively. With HA addition, the porosity decreased and pore shape became more irregular. The HA particulates, in sizes of about 2-5 microm, were distributed within the gelatin network homogeneously and made the framework surface rougher. All the foams had high water absorption capacities, showing typical hydrogel characteristics, even though the HA addition decreased the degree of water absorption. The HA addition made the foam much stronger and stiffer (i.e., with increasing HA amount the foams sustained higher compressive stress and had higher elastic modulus in both dry and wet states). The osteoblast-like human osteosarcoma cells spread and grew actively on all the foams. The cell proliferation rate, quantified indirectly on the cells cultured on Ti discs coated with gelatin and gelatin-HA composites using MTT assay, exhibited an up-regulation with gelatin coating compared with bare Ti substrate, but a slight decrease on the composite coatings. However, the alkaline phosphatase activities expressed by the cells cultured on composites foams as well as their coatings on Ti discs were significantly enhanced compared with those on pure gelatin foam and coating. These findings suggest that the gelatin-HA composite foams have great potential for use as hard tissue regeneration scaffolds.

Animals↗

Hydroxyapatite and titania sol-gel composite coatings on titanium for hard tissue implants; mechanical and in vitro biological performance.

Hydroxyapatite (HA) composites with titania (TiO2) up to 30 mol % were coated on a titanium (Ti) substrate by a sol-gel route, and the mechanical and biological properties of the coating systems were evaluated. Using polymeric precursors, highly stable HA and TiO2 sols were prepared prior to making composite sols and coatings. Coatings were produced under a controlled spinning and heat treatment process. Pure phases of HA and TiO2 were well developed on the composites after heat treatment above 450 degrees C. The HA-TiO2 composite coating layers were homogeneous and highly dense with a thickness of about 800-900 nm. The adhesion strength of the coating layers with respect to Ti substrate increased with increasing the TiO2 addition. The highest strength obtained was as high as 56 MPa, with an improvement of about 50% when compared to pure HA (37 MPa). The osteoblast-like cells grew and spread actively on all the composite coatings. The proliferation and alkaline phosphatase (ALP) activity of the cells grown on the composite coatings were much higher than those on bare Ti, and even comparable to those on pure HA coating. Notably, the HA-20% TiO2 composite coating showed a significantly higher proliferation and ALP expression compared to bare Ti (p < 0.05). These findings suggest that the sol-gel-derived HA-TiO2 composite coatings possess excellent properties for hard tissue applications from the mechanical and biological perspective.

Alkaline Phosphatase↗

Degradation and drug release of phosphate glass/polycaprolactone biological composites for hard-tissue regeneration.

Phosphate-based glass (P-glass) and poly(epsilon-caprolactone) (PCL) composites were fabricated in a sheet form by solvent extraction and thermal pressing methods, and the antibiotic drug Vancomycin was loaded within the composites for use as a hard-tissue regenerative. The degradation and drug-release rate of the composites in vitro were tailored by modifying the glass composition: 0.45 P(2)O(5)-x CaO-(0.55-x)Na(2)O, where x=0.2, 0.3, 0.4, and 0.5. Compared to pure PCL, all the P-glass/PCL composites degraded to a higher degree, and the composite with lower-CaO glass showed a higher material loss. This was attributed mainly to the dissolution of the glass component. The glass dissolution also increased the degradation of PCL component in the composites. The Vancomycin release from the composites was strongly dependent on the glass composition. Drug release in pure PCL was initially abrupt and flattened out over a prolonged period. However, glass/PCL composites (particularly in the glass containing higher-CaO) exhibited a reduced initial burst and a higher release rate later. Preliminary cell tests on the extracts from the glass/PCL composites showed favorable cell proliferation, but the level was dependent on the ionic concentration of the extracts. The cell proliferation on the diluted extracts from the composite with higher-CaO glass was significantly higher than that on the blank culture dish. These observations confirmed that the P-glass/PCL composites are potentially applicable for use as hard-tissue regeneration and wound-healing materials because of their controlled degradation and drug-release profile as well as enhanced cell viability.

Biocompatible Materials↗

Porous scaffolds of gelatin-hydroxyapatite nanocomposites obtained by biomimetic approach: characterization and antibiotic drug release.

Gelatin-hydroxyapatite (HA) nanocomposite porous scaffolds were fabricated biomimetically, and their feasibility as a drug-delivery carrier for tissue-regeneration and wound-healing treatments was addressed. The composite sols were prepared by the precipitation of HA up to 30 wt % within a gelatin solution with the use of calcium and phosphate precursors, and the porous scaffold was obtained by casting the sols and further freeze drying. The obtained bodies were crosslinked with carbodiimide derivatives to retain chemical and thermal integrity. The apatite precipitates were observed to be a poorly crystallized carbonate-substituted HA. The nanocomposite scaffolds had porosities of approximately 89-92% and exhibited a bimodal pore distribution, that is, the macropores (approximately 300-500 microm) of the framework structure, and micropores (approximately 0.5-1 microm) formed on the framework surface. Transmission electron microscopy (TEM) observation revealed the precipitation of highly elongated HA nanocrystals on the gelatin network. The well-developed porous structure and organized nanocomposite configurations were in marked contrast to the directly mixed gelatin-HA powder conventional composites. For drug-release tests, tetracycline, an antibiotic drug, was entrapped within the scaffold, and the drug-release profile was examined with processing parameters, such as HA amount in gelatin, crosslinking degree, and initial drug addition. The drug entrapment decreased with increasing HA amount, but increased with increasing crosslinking degree and initial drug addition. The crosslinking of the gelatin was the prerequisite to sustaining and controlling the drug releases. Compared to pure gelatin, the gelatin-HA nanocomposites had lower drug releases, because of their lower water uptake and degradation. All the nanocomposite scaffolds released drugs in proportion to the initial drug addition, suggesting their capacity to deliver drugs in a controlled manner. Based on the findings of the well-developed morphological feature and controlled drug-release profile, the gelatin-HA nanocomposite porous scaffolds are suggested to be potentially useful for hard-tissue regeneration.

Anti-Bacterial Agents↗

Fluoride coatings on orthodontic wire for controlled release of fluorine ion.

The purpose of this study was to develop a new method of releasing fluorine in a controlled manner for applications in the field of orthodontic Ti-based wire, namely the coating of fluorides on Ti. Thin films of two fluoride compounds, CaF(2) and MgF(2), were coated on Ti via the electron-beam evaporation method. The fluorine was released rapidly from the as-deposited MgF(2) coating within a short period(,) and then the release rate slowed down. When the MgF(2) coating was heat treated, this initial burst effect was decreased, but a significant amount of cracks were generated. On the other hand, in the case of the as-deposited CaF(2) coating, fluorine was released linearly for the entire period, without an initial burst. In the heat-treated CaF(2) coatings the trend was similarly observed. The linear fluorine release from the CaF(2) coatings, even in the as-deposited state, was attributed to the high degree of crystallinity of the coatings. A preliminary cell test showed favorable cell viability on both the fluoride coatings. Given their sustained and controlled fluorine release, these fluoride coatings, particularly CaF(2), are suggested to be potentially useful in the field of orthodontic Ti-based wire.

Cell Line, Tumor↗

Microsphere of apatite-gelatin nanocomposite as bone regenerative filler.

In this study, we developed novel microspheres comprised of an apatite-gelatin nanocomposite. This microsphere formulation is considered to be useful as a bone regenerative filler, either directly or combined with polymeric matrices. Using the water-in-oil emulsion technique, the apatite-gelatin viscous nanocomposite solution was successfully formulated into microspheres with an average diameter of approximately 110 microm. The microspheres were composed of apatite nanocrystallines precipitated within the gelatin matrix, revealing a typical nanocomposite internal structure. This nanocomposite structure contrasted markedly with that of the conventional composite microspheres which were obtained by directly mixing gelatin with apatite powder. Initial cellular assays showed that the microspheres maintained the adhesion and proliferation of the osteoblastic cells, suggesting the usefulness of the apatite-gelatin nanocomposite microspheres in the bone regeneration field.

Apatites↗