• Macromolecular Research
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• v.11 no.4
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• pp.207-223
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• 2003

For last five years, we are developing the novel local drug delivery devices using biodegradable polymers, especially polylactide (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) due to its relatively good biocompatibility, easily controlled biodegradability, good processability and only FDA approved synthetic degradable polymers. The relationship between various kinds of drug [water soluble small molecule drugs: gentamicin sulfate (GS), fentanyl citrate (FC), BCNU, azidothymidine (AZT), pamidronate (ADP), $1,25(OH)_2$ vitamin $D_3$, water insoluble small molecule drugs: fentanyl, ipriflavone (IP) and nifedipine, and water soluble large peptide molecule drug: nerve growth factor (NGF), and Japanese encephalitis virus (JEV)], different types of geometrical devices [microspheres (MSs), microcapsule, nanoparticle, wafers, pellet, beads, multiple-layered beads, implants, fiber, scaffolds, and films], and pharmacological activity are proposed and discussed for the application of pharmaceutics and tissue engineering. Also, local drug delivery devices proposed in this work are introduced in view of preparation method, drug release behavior, biocompatibility, pharmacological effect, and animal studies. In conclusion, we can control the drug release profiles varying with the preparation, formulation and geometrical parameters. Moreover, any types of drug were successfully applicable to achieve linear sustained release from short period ($1{\sim}3$ days) to long period (over 2 months). It is very important to design a suitable formulation for the wanting period of bioactive molecules loaded in biodegradable polymers for the local delivery of drug. The drug release is affected by many factors such as hydrophilicity of drug, electric charge of drug, drug loading amount, polymer molecular weight, the monomer composition, the size of implants, the applied fabrication techniques, and so on. It is well known that the commercialization of new drug needs a lot of cost of money (average: over 10 million US dollar per one drug) and time (average: above 9 years) whereas the development of DDS and high effective generic drug might be need relatively low investment with a short time period. Also, one core technology of DDS can be applicable to many drugs for the market needs. From these reasons, the DDS research on potent generic drugs might be suitable for less risk and high return.

• Korean Journal of Materials Research
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• v.20 no.6
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• pp.331-337
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• 2010

A highly porous Biphasic Calcium Phosphate (BCP) scaffold was fabricated by the sponge replica method with a microwave sintering technique. The BCP scaffold had interconnected pores ranging from $80\;{\mu}m$ to $1000\;{\mu}m$, which were similar to natural cancellous bone. To enhance the mechanical properties of the porous scaffold, infiltration of polycaprolactone (PCL) was employed. The microstructure of the BCP scaffold was optimized using various volume percentages of polymethylmethacrylate (PMMA) for the infiltration process. PCL successfully infiltrated into the hollow space of the strut formed after the removal of the polymer sponge throughout the degassing and high pressure steps. The microstructure and material properties of the BCP scaffold (i.e., pore size, morphology of infiltrated and coated PCL, compressive strength, and porosity) were evaluated. When a 30 vol% of PMMA was used, the PCL-BCP scaffold showed the highest compressive strength. The compressive strength values of the BCP and PCL-BCP scaffolds were approximately 1.3 and 2MPa, respectively. After the PCL infiltration process, the porosity of the PCL-BCP scaffold decreased slightly to 86%, whereas that of the BCP scaffold was 86%. The number of pores in the $10\;{\mu}m$ to $20\;{\mu}m$ rage, which represent the pore channel inside of the strut, significantly decreased. The in-vitro study confirmed that the PCL-infiltrated BCP scaffold showed comparable cell viability without any cytotoxic behavior.

• Macromolecular Research
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• v.17 no.12
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• pp.1025-1031
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• 2009

Several kinds of biodegradable hydrogels were prepared via in situ photopolymerization of Pluronic F127/poly($\varepsilon$-caprolactone) macromer and acrylic acid (AA) comonomer in aqueous medium. The swelling kinetics measurements showed that the resultant hydrogels exhibited both thermo- and pH-sensitive behaviors, and that this stimuli-responsiveness underwent a fast reversible process. With increasing pH of the local buffer solutions, the pH sensitivity of the hydrogels was increased, while the temperature sensitivity was decreased. In vitro hydrolytic degradation in the buffer solution (pH 7.4, $37^{\circ}C$), the degradation rate of the hydrogels was greatly improved due to the introduction of the AA comonomer. The in vitro release profiles of bovine serum albumin (BSA) in-situ embedded into the hydrogels were also investigated: the release mechanism of BSA based on the Peppas equation was followed Case II diffusion. Such biodegradable dual-sensitive hydrogel materials may have more advantages as a potentially interesting platform for smart drug delivery carriers and tissue engineering scaffolds.

• KSBB Journal
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• v.22 no.4
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• pp.179-184
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• 2007

This study introduces the characteristics and some applications of repetitive polypeptides, especially to the biomaterial, tissue engineering scaffolds, drug delivery system, and DNA separation systems. Since some fibrous proteins, which consist of repeating peptide monomers, have been reported that their physical properties are changed dramatically by means of temperature alteration or pH shifting. For that reason, fibrous protein-mimetic polypeptides, which are produced by the recombinant technology, can be applied to the diverse biological fields. Repetitive polypeptides can also be used in the bioseparation area such as DNA sequencing, because they make DNA separation possible in free-solution electrophoresis by conjugating DNA fragments to them. Moreover, artificial synthesis of repetitive polypeptides helps to demonstrate the correlations between mechanical properties and structures of natural protein polymer, which have been proven that repetitive domains are affected by the sequence of the repeating domains and the number of repeating subunits. Repetitive polypeptides can be biologically synthesized using some special cloning methods, which are represented here. Recursive directional ligation (RDL) and controlled cloning method (CCM) have been proposed as excellent cloning methods in that we can control the number of repetition in the multimerization of polypeptides and the components of repetitive polypeptides by either method.

• Macromolecular Research
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• v.12 no.4
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• pp.367-373
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• 2004

We have developed a rigorous heat treatment method to improve the biocompatibility of chitosan as a tissue-engineered scaffold. The chitosan scaffold was prepared by the controlled freezing and lyophilizing method using dilute acetic acid and then it was heat-treated at 110$^{\circ}C$ in vacuo for 1-3 days. To explore changes in the physicochemical properties of the heat-treated scaffold, we analyzed the degree of deacetylation by colloid titration with poly(vinyl potassium sulfate) and the structural changes were analyzed by scanning electron microscopy, Fourier transform infrared (FT-IR) spectroscopy, wide-angle X-ray diffractometry (WAXD), and lysozyme susceptibility. The degree of deacetylation of chitosan scaffolds decreased significantly from 85 to 30% as the heat treatment time increased. FT-IR spectroscopic and WAXD data indicated the formation of amide bonds between the amino groups of chitosan and acetic acids carbonyl group, and of interchain hydrogen bonding between the carbonyl groups in the C-6 residues of chitosan and the N-acetyl groups. Our rigorous heat treatment method causes the scaffold to become more susceptible to lysozyme treatment. We performed further examinations of the changes in the biocompatibility of the chitosan scaffold after rigorous heat treatment by measuring the initial cell binding capacity and cell growth rate. Human dermal fibroblasts (HDFs) adhere and spread more effectively to the heat-treated chitosan than to the untreated sample. When the cell growth of the HDFs on the film or the scaffold was analyzed by an MTT assay, we found that rigorous heat treatment stimulated cell growth by 1.5∼1.95-fold relative to that of the untreated chitosan. We conclude that the rigorous dry heat treatment process increases the biocompatibility of the chitosan scaffold by decreasing the degree of deacetylation and by increasing cell attachment and growth.

• Macromolecular Research
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• v.17 no.9
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• pp.703-708
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• 2009

Silk fibroin scaffolds were examined as a biomaterial option for tissue-engineered cartilage-like tissue. In tissue engineering for cartilage repair using a scaffold, initial chondrocyte-material interactions are important for the following cell behaviors. In this study, the surface of nanofibrous silk fibroin (NSF) meshes was modified by a microwave-induced argon plasma treatment in order to improve the cytocompatibility of the meshes used as cartilaginous grafts. In addition, the effects of a plasma treatment on the cellular behavior of chondrocytes on NSF were examined. The plasma treatment resulted in an increase in the hydrophilicity of NSF meshes suggesting that the cytocompatibility of the mesh might be improved. Furthermore, the human articular chondrocytes showed higher viability on the surface-modified NSF meshes. These results suggest that the surface modification of NSF meshes by plasma can enhance the cellular behavior of chondrocytes and may be used in tissue engineering.

• Macromolecular Research
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• v.16 no.6
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• pp.517-523
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• 2008

A RGD (Arg-Gly-Asp) conjugated chitosan hydrogel was used as a cell-supporting scaffold for articular cartilage regeneration. Thermosensitive chitosan-Pluronic (CP) has potential biomedical applications on account of its biocompatibility and injectability. A RGD-conjugated CP (RGD-CP) copolymer was prepared by coupling the carboxyl group in the peptide with the residual amine group in the CP copolymer. The chemical structure of RGD-CP was characterized by $^1H$ NMR and FT IR. The concentration of conjugated RGD was quantified by amino acid analysis (AAA) and rheology of the RGD-CP hydrogel was investigated. The amount of bound RGD was $0.135{\mu}g$ per 1 mg of CP copolymer. The viscoelastic parameters of RGD-CP hydrogel showed thermo-sensitivity and suitable mechanical strength at body temperature for cell scaffolds (a> 100 kPa storage modulus). The viability of the bovine chondrocyte and the amount of synthesized glycosaminoglycans (GAGs) on the RGD-CP hydrogels were evaluated together with the alginate hydrogels as a control over a 14 day period. Both results showed that the RGD-CP hydrogel was superior to the alginate hydrogel. These results show that conjugating RGD to CP hydro gels improves cell viability and proliferation, including extra cellular matrix (ECM) expression. Therefore, RGD conjugated CP hydrogels are quite suitable for a chondrocyte culture and have potential applications to the tissue engineering of articular cartilage tissue.

• Polymer(Korea)
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• v.39 no.3
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• pp.418-425
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• 2015

Polycaprolactone (PCL) and biphasic calcium phosphate (BCP) have been considered as useful materials for orthopedic devices and osseous implants because of their biocompatibility and bone-forming activity. However, PCL-based scaffolds have hydrophobic surfaces reducing initial cell adhesion or proliferation. To overcome the limitation, we fabricated surface-modified PCL/BCP nanofibers using gamma-irradiation for bone tissue engineering. PCL/BCP nanofibers were prepared by electrospinning and then we supplemented hydrophilicity by introducing acrylic acid (AAc) through gamma-irradiation. We confirmed the surface of nanofibers by SEM, and then the initial viability of MG63 was significantly increased on the AAc grafted nanofibers, and alkaline phosphatase activity($1.239{\pm}0.226nmole/{\mu}g/min$) improved on the modified nanofibers than that on the non-modified nanofibers($0.590{\pm}0.286nmole/{\mu}g/min$). Therefore, AAc-grafted nanofibers may be a good tool for bone tissue engineering applications.

• Journal of Periodontal and Implant Science
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• v.31 no.1
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• pp.1-23
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• 2001

Chitosan is biodegradable natural polymer that has been demonstrated its ability to improve wound healing, and calcium metaphosphate(CMP) is a unique class of phosphate minerals having a polymeric structure. In this study, chitosan/CMP and platelet derived growth factor(PDGF-BB) loaded chitosan/CMP sponges were developed, and the effect of the sponges on bone regeneration and their possibility as scaffolds for bone formation by three-dimensional osteoblast culture were examined. PDGF-BB loaded chitosan/CMP sponges were prepared by freeze-drying of a mixture of chitosan solution and CMP powder, and soaking in a PDGF-BB solution. Fabricated sponge retained its 3-dimensional porous structure with $100-200\;{\mu}m$ pores. The release kinetics of PDGF-BB loaded onto the sponge were measured in vitro with $^{125}I-labeled$ PDGF-BB. In order to examine their possibility as scaffolds for bone formation, fetal rat calvarial osteoblastic cells were isolated, cultured, and seeded into the sponges. The cell-sponge constructs were cultured for 28 days. Cell proliferation, alkaline phosphatase activity were measured at 1, 7, 14 and 28 days, and histologic examination was performed. In order to examine the effect on the healing of bone defect, the sponges were implanted into rat calvarial defects. Rats were sacrificed 2 and 4 weeks after implantation and histologic and histomorphometrical examination were performed. An effective therapeutic concentration of PDGF-BB following a high initial burst release was maintained throughout the examination period. PDGF-BB loaded chitosan/CMP sponges supported the proliferation of seeded osteoblastic cells as well as their differentiation as indicated by high alkaline phosphatase activities. Histologic findings indicated that seeded osteoblastic cells well attached to sponge matrices and proliferated in a multi-layer fashion. In the experiments of implantation in rat calvarial defects, histologic and histomorphometric examination revealed that chitosan/CMP sponge promoted osseous healing as compared to controls. PDGF-BB loaded chitosan/CMP sponge further echanced bone regeneration. These results suggested that PDGF-BB loaded chitosan/CMP sponge was a feasable scaffolding material to grow osteoblast in a three-dimentional structure for transplantation into a site for bone regeneration.