ABSTRACT: Our previous studies showed that a mechano-active scaffold made of poly(L-lactide-co-epsilon-caprolactone) (PLCL) exhibited a high potential to realize the formation of a functional, engineered cartilage in vitro. This animal study therefore was designed to investigate the feasibility of repairing on osteochondral defect with the use of bone marrow-derived mesenchymal stem cells (BMSCs) incorporated with a PLCL scaffold. Rabbit BMSCs, isolated and subsequently cultured in monolayer, were seeded into a porous PLCL scaffold sponge following an implantation onto a full-thickness osteochondral defect (diameter of 4.5 mm, depth of 5 mm) that was artificially created on the medial femoral condyles at a high load-bearing site on a rabbit's knee joint. Time-dependent healing of the defect was evaluated by macroscopic, histological examinations at both 3- and 6-month-implantations, respectively. A PLCL sponge incorporated with BMSCs exhibited sufficient structural support, resulting in new osteochondral tissue regeneration: a physiologically well-integrated subchondral bone formation, a hyaline cartilage-like morphology containing chondrocytes surrounded by abundant cartilaginous matrices. In addition, quantitative biochemical assays also demonstrated high potential for the synthesis of sulfated glycosaminoglycan and collagen, both of which are biomolecules essential to extracelluar matrix in normal cartilage tissue. In contrast, defects filled with cell-free PLCL scaffold or left empty showed a very limited potential for regeneration. Our findings suggest that a composite of PLCL-based sponge scaffold and BMSCs promote the repair of osteochondral defects at high load-bearing sites in adult rabbits.
Journal of Biomedical Materials Research Part B Applied Biomaterials 03/2010; 94(1):80-8. · 2.15 Impact Factor
ABSTRACT: We investigated the mechanisms of shear stress (SS)-induced activation of cytochrome P450 (CYP) 1A1 and cell cycle arrest with regard to the role of the aryl hydrocarbon receptor (AhR), since AhR mediates the expression of CYP1A1 induced by polycyclic aromatic hydrocarbons (PAHs) and is thought to be involved in the regulation of cell growth and differentiation.
Human umbilical vein endothelial cells (ECs) were exposed to laminar SS and thereafter collected to evaluate the expression, activity, and transcription of CYP1A1 and the expression of AhR and cell cycle-related proteins. A physiological level of laminar SS (15 dynes/cm(2)) markedly increased the expression level and enzymatic activity of CYP1A1. SS stimulated CYP1A1 promoter activity without influencing mRNA stability. Loss of two functional xenobiotic response elements (XREs) in the 5'-flanking region of the CYP1A1 gene suppressed the SS-induced transcription of CYP1A1. Laminar SS stimulated the expression and nuclear translocation of AhR. alpha-Naphthoflavone, an AhR antagonist, and a small interfering RNA (siRNA) for AhR significantly suppressed SS-induced CYP1A1 expression. The siRNA also abolished SS-induced cell cycle arrest, the expression of the cyclin-dependent kinase inhibitor p21(Cip1), and dephosphorylation of retinoblastoma protein.
Laminar SS stimulated the transcription of CYP1A1 through the activation of AhR in a way that is similar to the effects of PAHs. AhR was also involved in cell cycle arrest induced by SS. Our results suggest that sustained activation of AhR exposed to blood flow plays an important role in the regulation of EC functions.
Cardiovascular Research 04/2008; 77(4):809-18. · 6.06 Impact Factor
ABSTRACT: The temporal response of young rabbit chondrocyte metabolism (including biosynthesis of extracellular matrix macromolecules such as collagen and aggrecan, both of which are essential components of normal cartilage tissue, and their messenger ribonucleic acid (mRNA) expression) in microporous elastomeric scaffolds made of poly(L-lactide-co-epsilon-caprolactone) subjected to different compressive regimes (loading frequency, loading duration per cycle, loading period, and continuous or intermittent compression) were studied over a 6-day culture period at 10% of compressive strain. A continuous dynamic compression improved the production of sulfated glycosaminoglycan (S-GAG), most of which was released into the culture medium upon loading. High mRNA expression of type II collagen was exhibited at a frequency of 0.1 Hz. Little frequency dependency was observed for aggrecan. An intermittent loading (24-h cycle of loading and unloading) or short loading and unloading duration per cycle-compression regime maintained high levels of mRNA expression. This strongly suggests that well-controlled mechanical conditioning regimes may control the gene expression of key metabolic substances relevant to functional cartilage tissue while the degree of release of these substances into the culture medium is minimized.
Tissue Engineering 02/2007; 13(1):29-40. · 4.02 Impact Factor
ABSTRACT: A new approach for simulating quantum transport in nanoscale
semiconductor devices is presented. The method is based on the
self-consistent solution of the Poisson and Wigner equations within a
device. The spherical harmonic approach is used to transform the Wigner
equation into a tractable expression. The results provide the
distribution function and its averages throughout the device. The method
has been applied to a MOSFET and a BJT. Inclusion of quantum effects
reduces carrier concentrations near potential energy barriers, leading
to reduced terminal current
Simulation of Semiconductor Processes and Devices, 2000. SISPAD 2000. 2000 International Conference on; 02/2000
ABSTRACT: As device dimensions shrink toward 0.1 μm, gate oxides are
becoming so thin that MOSFET gate leakage current and oxide degradation
are becoming limiting issues. We provide a more rigorous way to
calculate gate leakage current. To achieve this we build upon the
Spherical Harmonic Method of modeling, which deterministically solves
the Boltzmann equation for an entire device. The method gives the
distribution function and is 1000 times faster than MC. Once the
distribution function is calculated, the tunneling probability is
derived from the first principle WKB method. The barrier lowering effect
is accounted for by the method of image charges. We calculate gate
leakage current as a function of DC bias. The thermionic and tunneling
components are compared at different DC bias points. The dependence of
gate leakage current on gate oxide thickness is simulated
Simulation of Semiconductor Processes and Devices, 1999. SISPAD '99. 1999 International Conference on; 02/1999
ABSTRACT: Recent advances in the Spherical Harmonic Boltzmann method of device modeling are presented. A new surface scattering model and improved numerical interpolation schemes have been developed. The method is shown to be capable of calibrating an entire deep submicron process to provide I–V characteristics and substrate current self-consistently. Substrate currents agree with experiment over a complete process without any fitting parameters. Applications to a 50 nm MOSFET predict well-behaved device operation. The method requires approximately ten minutes to self-consistently calculate a MOSFET bias point and provide the device distribution function. The spherical harmonic method has been extended to account for quantum mechanical effects by applying it to the Wigner equation. We treat the Wigner equation as a quantum correction to the Boltzmann equation thereby making the spherical harmonic approach a natural method of solution.
Superlattices and Microstructures.