Abstract: In bone tissue engineering, porous scaffolds served as the temporary matrix are often
subjected to mechanical stress when implanted in the body. Based on this fact, the goal of this study
was to examine the effects of mechanical loading on the in vitro degradation characteristics and
kinetics of porous scaffolds in a custom-designed loading system. Porous Poly(L-lactic
acid)/β-Tricalcium Phosphate (PLLA/β-TCP) composite scaffolds fabricated by using solution
casting/compression molding/particulate leaching technique (SCP) were subjected to degradation in
simulated body fluid (SBF) at 37°C for up to 6 weeks under the conditions: with and without static
compressive loading, respectively. The results indicated that the increase of the porosity and
decrease of the compressive strength under static compressive loading were slower than that of
non-loading case, and so did the mass loss rate. It might be due to that the loading retarded the
penetration, absorption and transfer of simulated body fluid. These data provide an important step
towards understanding mechanical loading factors contributing to degradation.
Abstract: Biomaterials Center is composed of five groups and collaborate each other to examine
interdisciplinary fields of biomaterials. In the ceramics-based biomaterials research, we have been
developing three novel bone regeneration materials, i.e., high-porosity hydroxyapatite (HAp)
ceramics with high-strength, guided bone regeneration (GBR) membranes and bone-like
nanocomposite composed of HAp and collagen. The GBR membrane composed of β-tricalcium
phosphate and biodegradable copolymer of lactide, glycolide and ε-caprolactone has thermoplastic,
pH auto-adjustment and enough mechanical property to protect an invasion of surrounding tissues.
With the membrane, bone defect up to 20 × 10 × 10 mm3 in length in mandibles and segmental
bone defect up to 20 mm in length in tibiae of beagles are regenerated without any additional bone
fillers or cell transplantations. The bone-like nanocomposite is synthesized by a co-precipitation of
HAp and collagen via their self-organization. The dense composite has a half to quarter mechanical
strength (40 MPa) to cortical bone and the porous one demonstrates sponge-like viscoelasticity.
The composites implanted into bone are incorporated into bone remodeling metabolism like as
autogenous bone graft, i.e., they are resorbed by osteolasts followed by osteogenesis by osteoblasts.
Abstract: In this study, muscle-derived stem cell (MDSC)/Pluronics/polycaprolactone (PCL)
microparticle hybrid mixture was prepared as a potential injectable urethral bulking agent for the
treatment of urinary incontinence. The MDSCs were isolated from the gastrocnemius muscles of
SD rats by a modified preplate method and characterized through FACS analysis using various
primary antibodies (CD34, Sca-1, CD45 and desmin). The hybrid mixture was prepared by the
mixing of PCL microparticles (diameter, 100~200 μm) and MDSCs-containing thermo-sensitive
Pluronic (F127/F68 mixture) solution (4.5/5.5, w/v). The hybrid mixture was easily injected
through 18G needle into the body and stably remained in the applied site without initial volume
decrease, owing to a well-packed structure of PCL particles exhibited in the hybrid mixture. It was
observed that the MDSCs were stably grown in the hybrid mixture without severe inflammation and
immune reaction. From the results, we recognized that the hybrid mixture can be a good candidate
as an injectable bulking agent for the treatment of urinary incontinence, due to their good
injectability, volume retention and biocompatibility.
Abstract: Chitosan cylindrical scaffolds with gradually increasing pore size along the longitudinal
direction were fabricated by a novel centrifugation method to investigate pore size effect on cell
interactions. The scaffold was fabricated by the centrifugation of a cylindrical mold containing fibril-like
chitosans. The pore size ranges of the scaffold could be controlled by adjusting the centrifugal speed: the
scaffold with gradually increasing pore size (from ~80 #m to ~400 #m) and porosity (from ~82 % to
~93 %) along the cylindrical axis was obtained by applying the centrifugal speed, 3,000 rpm. The scaffold
sections were examined for their in vitro cell interactions using different kinds of cells (fibroblasts,
chondrocytes, and osteoblasts) in terms of scaffold pore sizes. It was observed that different kinds of cells
were shown to have different pore size ranges in the scaffold for effective cell growth. The chitosan
scaffold section with ~400 #m pore size showed better cell growth for chondrocytes and osteoblasts,
while the scaffold section with ~190 #m pore size was better for fibroblast growth. The pore size gradient
scaffolds fabricated by the centrifugation method can be a good tool for the systematic studies of the
interactions between cells or tissues and scaffolds with different pore size.
Abstract: Porous polydioxanone (PDO)/polyvinyl alcohol (PVA) scaffolds were fabricated by
blending PDO with a small amount of PVA to improve the hydrophilicity and cell/tissue
compatibility of the scaffolds for tissue engineering applications. PDO/PVA scaffolds with different
PVA compositions up to 10 wt% were fabricated by a melt-molding particulate-leaching method
(non-solvent method). The prepared scaffolds exhibited highly porous, uniform open-cellular pore
structures. The PDO/PVA scaffolds with PVA compositions more than 5 % were easily wetted in
cell culture medium. The hydrophilized PDO/PVA (5 wt%) scaffold showed better cell adhesion
and growth than the control hydrophobic PDO scaffold. The PDO/PVA (5 wt%) scaffold also
showed faster tissue infiltration into the scaffold than the PDO scaffold. It seems that 5 wt%
addition of PVA to PDO to fabricate PDO/PVA scaffolds is enough for improving the
hydrophilicity and cell/tissue compatibility of the scaffolds.
Abstract: Electrospinning is a fabrication process that can produce highly porous nano-scale fiber-based
matrices using an electrostatically driven jet of polymer solution. This method represents an attractive
approach for polymeric biomaterial processing which provides the membrane structure that may retain
mechanical strengths, flexibility, and high surface area. In this study, we prepared a guided bone
regeneration (GBR) membrane with selective permeability, hydrophilicity, good mechanical strength and
adhesiveness with bone using polycaprolactone (PCL) and Tween 80 by the electrospinning method. The
prepared PCL and PCL/Tween 80 electrospun sheets were characterized via morphology observation,
mechanical property, water absorbability, and model nutrient permeability. It was observed that the
PCL/Tween 80 (3 wt%) electrospun sheet have an effective permeation of nutrients as well as the good
mechanical strength to maintain a secluded space for the bone regeneration. From the results, the
hydrophilized PCL/Tween 80 (3 wt%) electrospun sheet seem to be a good candidate as a GBR
Abstract: Biodegradable porous poly(L-lactic acid) (PLLA) scaffolds were prepared using gas
foaming method. The PLLA scaffolds with a hydrophobic surface were subjected to Ar plasma
treatment and in situ acrylic acid (AA) grafting to obtain hydrophilic PLLA scaffold (PLLA-PAA).
Cell-adhesive RGD peptide was then immobilized onto the AA-grafted PLLA (PLLA-PAA-RGD).
Once rabbit bone marrow-derived mesenchymal stem cells (BM-MSC) were isolated, MSCs were
seeded into PLLA control, PLLA-PAA, and PLLA-PAA-RGD scaffold and cultured for up to 4
weeks in chondrogenic medium with the addition of 10 ng/ml transforming growth factor (TGF)-β1.
Surface analysis of AA-grafted PLLA identified significant alterations of surface characteristics,
including reduced contact angle and different atomic compositions. From WST-1 assay at 4 weeks,
cells were found more proliferative in PLLA-PAA than the others. Upon the histological analysis of
Safranin O staining, chondrogenic differentiation of MSCs appeared to be progressed more actively
in PLLA-PAA. The effect of RGD immobilization on MSC differentiation was barely notable.
Abstract: Pluronic F127 has received increasing attention over many years as drug delivery
systems, biomaterials, and hydrogels for tissue engineering. In this study, we synthesized
temperature-sensitive and cell-adhesive triblock F127 copolymers, in which Arg-Gly-Asp (RGD)
peptide ligand was grafted to Pluronic F127-4-methacryloxyethyl trimellitic anhydride (4-META)
to obtain F127-META-RGD. The chemical structures of the F127-META-RGD block copolymers
were confirmed by FTIR, 1H and 13C NMR, and GPC. The resultant F127-META-RGD showed
very similar thermosensitive behaviors to F127 and F127-META. The critical micelle temperature
(CMT) of the F127 copolymers decreased in the order of F127 < F127-META <
F127-META-RGD, whereas the particle size followed an opposite trend. Interactions between the
F127 copolymers and adipose-derived stem cells (ASC) were evaluated in terms of cell adhesion
and proliferation on the hydrogel. These thermosensitive RGD-grafted Pluronic hydrogels that
display the enhanced cell adhesiveness, are expected to be useful as a functional injectable scaffold
for tissue engineering.
Abstract: In prior work we have shown that titanium oxide (Ti-O) thin films have good blood
compatibility. However, as well as being hemocompatible, biomaterials used in contact with blood
should be cell compatible also. In the work described here, Ti-O films were synthesized using
unbalanced magnetron sputtering (UBMS) and were modified by immobilizing laminin on the film
surface for improving human umbilical vein endothelial cell (HUVEC) adhesion and growth.
Scanning electron microscopy (SEM), Fourier Transform Infrared spectroscopy (FTIR) and
contact-angle measurements were used to investigate the surface characteristics of the Ti-O films
and the modified Ti-O films. The results suggest that Laminin can be biochemically immobilized on
the Ti-O film surface. The modified layer of Laminin can improve the hydrophilicity and wettability
of Ti-O films. In vitro HUVEC investigations reveal that Laminin immobilized on the film surface
greatly enhances cell adhesion and growth on Ti-O films.
Abstract: Macrophages play a critical role in inflammatory response to implanted biomaterials and
formation of restenosis. Macrophage adhesion may lead to macrophage activation and smooth
muscle cell proliferation. Titanium oxide films on stainless steel are potential biomaterials for
application to vascular stents. They have different influences on smooth muscle cell proliferation in
in vivo tests, which could be the main reason for restenosis, but the mechanism is not clear. In this
study we show that titanium oxide films can reduce inflammatory reaction with macrophages.
Unstimulated macrophages release small amounts of chemical substance such as NO and give slight
effect on smooth muscle cell proliferation.