Serum albumin level and abnormal corrected QT interval in patients with coronary artery disease and chronic kidney disease.

BACKGROUND: Lower concentrations of serum albumin appear to be associated with an increased risk of all-cause and cardiovascular mortality, coronary heart disease, heart failure and stroke. However, little is known about the relationship between serum albumin level and prolonged QT interval. AIM: To investigate whether lower serum albumin is associated with prolonged QT interval by recording 12-lead electrocardiography in patients with coronary artery disease and chronic kidney disease. METHODS: This study included 1383 consecutive patients with coronary artery disease and chronic kidney disease (841 with acute coronary syndrome and 542 with elective percutaneous coronary intervention patients) who were enrolled in a disease management programme. Twelve-lead electrocardiography was recorded in each subject. We assessed the relationship between albumin levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation. RESULTS: Patients with abnormal QTc interval had lower serum albumin levels than those with normal and borderline QTc intervals. Statistically significant negative associations were observed between serum albumin levels and QTc interval (ß = -0.211, P < 0.0001). Using multivariate and trend analyses, a lower concentration of serum albumin was independently associated with QTc prolongation in both the patients with acute coronary syndrome and elective percutaneous coronary intervention patients. CONCLUSION: Concentrations of serum albumin were significantly lower in the patients with an abnormal QTc interval and were associated with QTc prolongation. Further studies are needed to clarify whether lower serum albumin plays a role in the pathogenesis of QTc prolongation.

Ubiquitous Emergency Medical Service System Based on Wireless Biosensors, Traffic Information, and Wireless Communication Technologies: Development and Evaluation.

This study presents a new ubiquitous emergency medical service system (UEMS) that consists of a ubiquitous tele-diagnosis interface and a traffic guiding subsystem. The UEMS addresses unresolved issues of emergency medical services by managing the sensor wires for eliminating inconvenience for both patients and paramedics in an ambulance, providing ubiquitous accessibility of patients' biosignals in remote areas where the ambulance cannot arrive directly, and offering availability of real-time traffic information which can make the ambulance reach the destination within the shortest time. In the proposed system, patient's biosignals and real-time video, acquired by wireless biosensors and a webcam, can be simultaneously transmitted to an emergency room for pre-hospital treatment via WiMax/3.5 G networks. Performances of WiMax and 3.5 G, in terms of initialization time, data rate, and average end-to-end delay are evaluated and compared. A driver can choose the route of the shortest time among the suggested routes by Google Maps after inspecting the current traffic conditions based on real-time CCTV camera streams and traffic information. The destination address can be inputted vocally for easiness and safety in driving. A series of field test results validates the feasibility of the proposed system for application in real-life scenarios.

Evaluation of a rapid quantitative determination method of PSA concentration with gold immunochromatographic strips.

BACKGROUND: Prostate cancer remains the most common cancer in men. Qualitative or semi-quantitative immunochromatographic measurements of prostate specific antigen (PSA) have been shown to be simple, noninvasive and feasible. The aim of this study was to evaluate an optimized gold immunochromatographic strip device for the detection of PSA, in which the results can be analysed using a Chromogenic Rapid Test Reader to quantitatively assess the test results. METHODS: This reader measures the reflectance of the signal line via a charge-coupled device camera. For quantitative analysis, PSA concentration was computed via a calibration equation. Capillary blood samples from 305 men were evaluated, and two independent observers interpreted the test results after 12 min. Blood samples were also collected and tested with a conventional quantitative assay. RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of the PSA rapid quantitative test system were 100, 96.6, 89.5, 100, and 97.4 %, respectively. Reproducibility of the test was 99.2, and interobserver variation was 8 % with a false positive rate of 3.4 %. The correlation coefficient between the ordinary quantitative assay and the rapid quantitative test was 0.960. CONCLUSIONS: The PSA rapid quantitative test system provided results quickly and was easy to use, so that tests using this system can be easily performed at outpatient clinics or elsewhere. This system may also be useful for initial cancer screening and for point-of-care testing, because results can be obtained within 12 min and at a cost lower than that of conventional quantitative assays.

Mechanical characterization of human umbilical arteries by thick-walled models: Enhanced vascular compliance by removing an abluminal lining.

The decellularized human umbilical artery (HUA) is considered as a promising option for small-diameter, tissue-engineered vascular grafts (TEVGs). Our previous study showed that the HUA bears a thin, watertight lining on its outermost abluminal surface. Removal of this abluminal lining layer improves efficacy of the perfusion-assisted decellularization of the HUA and increases its compliance. As stress across the wall is believed to affect growth and remodeling of the TEVG, it is imperative to mechanically characterize the HUA using thick-walled models. Combining inflation experiments and computational methods, we investigate the mechanical properties of the HUA before and after the abluminal lining removal to examine the HUA's wall mechanics. The inflation tests of five HUAs were performed to obtain the mechanical and geometrical response of the vessel wall before and after the lining layer removal. Using nonlinear hyperelastic models, the same responses are obtained computationally using the thick-walled models. The experimental data are incorporated into the computational models to estimate the mechanical and orientation parameters of the fibers and isotropic matrix of different layers in the HUAs. The parameter fitting of both thick-walled models (before and after the abluminal lining removal) results in most of the R-squared values for measuring the goodness of fitting to be over 0.90 for all samples. The compliance of the HUA increases from a mean value of 2.60% per 100 mmHg before the removal of the lining to a mean value of 4.21% per 100 mmHg after the removal. The results reveal that, although the abluminal lining is thin, it is stiff and capable of supporting majority of the high luminal pressure, and that the inner layer is far less stressed than the abluminal lining. Computational simulations also show that removal of the abluminal lining increases the circumferential wall stress by up to 280 kPa under the in vivo luminal pressure. The integrated computational and experimental approaches provide more accurate estimates of the material behaviors of HUAs employed in grafts and, in turn, the study enhances our understanding of interactions between the graft and the native vessel on vascular growth and remodeling.

A comparison of epithelial cells, fibroblasts, and osteoblasts in dental implant titanium topographies.

The major challenge for dental implants is achieving optimal esthetic appearance and a concept to fulfill this criterion is evaluated. The key to an esthetically pleasing appearance lies in the properly manage the soft tissue profile around dental implants. A novel implant restoration technique on the surface was proposed as a way to augment both soft- and hard-tissue profiles at potential implant sites. Different levels of roughness can be attained by sandblasting and acid etching, and a tetracalcium phosphate was used to supply the ions. In particular, the early stage attaching and repopulating abilities of bone cell osteoblasts (MC3T3-E1), fibroblasts (NIH 3T3), and epithelial cells (XB-2) were evaluated. The results showed that XB-2 cell adhesive qualities of a smooth surface were better than those of the roughened surfaces, the proliferative properties were reversed. The effects of roughness on the characteristics of 3T3 cells were opposite to the result for XB-2 cells. E1 proliferative ability did not differ with any statistical significance. These results suggest that a rougher surface which provided calcium and phosphate ions have the ability to enhance the proliferation of osteoblast and the inhibition of fibroblast growth that enhance implant success ratios.

Incorporation of Glutamic Acid or Amino-Protected Glutamic Acid into Poly(Glycerol Sebacate): Synthesis and Characterization.

Poly(glycerol sebacate) (PGS), a soft, tough elastomer with excellent biocompatibility, has been exploited successfully in many tissue engineering applications. Although tunable to some extent, the rapid in vivo degradation kinetics of PGS is not compatible with the healing rate of some tissues. The incorporation of L-glutamic acid into a PGS network with an aim to retard the degradation rate of PGS through the formation of peptide bonds was conducted in this study. A series of poly(glycerol sebacate glutamate) (PGSE) containing various molar ratios of sebacic acid/L-glutamic acid were synthesized. Two kinds of amino-protected glutamic acids, Boc-L-glutamic acid and Z-L-glutamic acid were used to prepare controls that consist of no peptide bonds, denoted as PGSE-B and PGSE-Z, respectively. The prepolymers were characterized using 1H-NMR spectroscopy. Cured elastomers were characterized using FT-IR, DSC, TGA, mechanical testing, and contact angle measurement. In vitro enzymatic degradation of PGSE over a period of 28 days was investigated. FT-IR spectroscopy confirmed the formation of peptide bonds. The glass transition temperature for the elastomer was found to increase as the ratio of sebacic acid/glutamic acid was increased to four. The decomposition temperature of the elastomer decreased as the amount of glutamic acid was increased. PGSE exhibited less stiffness and larger elongation at break as the ratio of sebacic acid/glutamic acid was decreased. Notably, PGSE-Z was stiffer and had smaller elongation at break than PGSE and PGSE-B at the same molar ratio of monomers. The results of in vitro enzymatic degradation demonstrated that PGSE has a lower degradation rate than does PGS, whereas PGSE-B and PGSE-Z degrade at a greater rate than does PGS. SEM images suggest that the degradation of these crosslinked elastomers is due to surface erosion. The cytocompatibility of PGSE was considered acceptable although slightly lower than that of PGS. The altered mechanical properties and retarded degradation kinetics for PGSE reflect the influence of peptide bonds formed by the introduction of L-glutamic acid. PGSE displaying a lower degradation rate compared to that for PGS can be used as a scaffold material for the repair or regeneration of tissues that are featured by a low healing rate.

Injectability, Processability, Drug Loading, and Antibacterial Activity of Gentamicin-Impregnated Mesoporous Bioactive Glass Composite Calcium Phosphate Bone Cement In Vitro.

Calcium phosphate cement (CPC) is similar to bone in composition and has plasticity, while mesoporous bioactive glass (MBG) has the advantage of releasing Si, which can promote osteogenic properties and drug loading capacity. A sol-gel-prepared MBG micro-powder (mMBG) and further impregnated antibiotic gentamicin sulfate (Genta@mMBG: 2, 3, and 4 mg/mL) antibiotic were added to CPC at different weight ratios (5, 10, and 15 wt.%) to study CPC's potential clinical applications. Different ratios of mMBG/CPC composite bone cement showed good injectability and disintegration resistance, but with increasing mMBG addition, the working/setting time and compressive strength decreased. The maximum additive amount was 10 wt.% mMBG due to the working time of ~5 min, the setting time of ~10 min, and the compressive strength of ~51 MPa, indicating that it was more suitable for clinical surgical applications than the other groups. The 2Genta@mMBG group loaded with 2 mg/mL gentamicin had good antibacterial activity, and the 10 wt.% 2Genta@mMBG/CPC composite bone cement still had good antibacterial activity but reduced the initial release of Genta. 2Genta@mMBG was found to have slight cytotoxicity, so 2Genta@mMBG was composited into CPC to improve the biocompatibility and to endow CPC with more advantages for clinical application.

[Correlation between age-related hearing loss and impairment of cognition in C57BL/6J mice].

OBJECTIVE: To explore the correlation of age-related hearing loss and cognition impairment in C57BL/6J mice by observing hearing, cognitive function and synapses. METHODS: C57BL/6J and CBA/CaJ mice were divided into 3 groups. The hearing and cognitive functions of each animal was tested. And the ultrastructure of synapses was simultaneously observed for C57BL/6J mice. RESULTS: The 24-26-week-old C57BL/6J mice developed moderate hearing loss while the 42-44-week-old C57BL/6J counterparts suffered profound hearing loss. Whereas excellent hearing was maintained in 3 groups of CBA/CaJ mice within 44 weeks. During cognitive test, the performance of 42-44-week-old C57BL/6J mice was significantly worse than CBA/CaJ mice. During probe test, the number of platform crossing of 42-44-week-old C57BL/6J mice was smaller than that of CBA/CaJ mice (0.5 ± 0.6 vs 1.9 ± 1.6; P < 0.05). The 42-44-week-old C57BL/6J mice had a wider synaptic cleft and a thinner postsynaptic density than the 24-26-week-old C57BL/6J counterparts [synaptic cleft: (19.4 ± 0.5) nm vs (11.9 ± 0.7) nm; postsynaptic density: (15.2 ± 0.5) nm vs (27.8 ± 2.0) nm; both P < 0.05]. Furthermore, the degeneration of synapses in hippocampus CA3 area of C57BL/6J mice were clearly observed at 42 - 44 weeks of age, but not seen in CBA/CaJ mice. CONCLUSION: Age-related hearing loss might impact on the cognition impairment in C57BL/6J mice.

Sub-100-micron calcium-alginate microspheres: Preparation by nitrogen flow focusing, dependence of spherical shape on gas streams and a drug carrier using acetaminophen as a model drug.

We developed a miniature gas-liquid coaxial flow device using glass capillaries, aiming to produce sub-100-µm Ca-alginate microspheres. Depending on collecting distance and the flow rates of nitrogen gas and alginate solution, however, Ca-alginate microparticles of different shapes were obtained. Spherical, monodisperse microparticles (microspheres) could only be obtained at certain gas flow rates and within a corresponding range of collecting distance. The result suggests that, for particles of this size, the gas flow rate and collecting distance are crucial for the formation of the spherical shape. We evaluated, as an example of its applications, the microsphere as a drug carrier using acetaminophen as a model drug. Large (~150 µm) and small (~70 µm) drug-loaded microspheres were prepared using two respective devices. Specifically, the drug-loaded microspheres were complexed with chitosan of different molecular weights. The dependence of in vitro drug release on the microsphere size and the chitosan molecular weight was examined. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Alginic acid sodium salt (PubChem CID: 5102882); Chitosan (PubChem CID: 71853); Calcium chloride (PubChem CID: 5284359); Sodium chloride (PubChem CID: 5234); Acetaminophen (PubChem CID: 1983); Polydimethylsiloxane (PubChem CID: 24771); n-Octadecyltrimethoxysilane (PubChem CID: 76486).

Synthesis, Characterization, and Electrospinning of a Functionalizable, Polycaprolactone-Based Polyurethane for Soft Tissue Engineering.

We synthesized a biodegradable, elastomeric, and functionalizable polyurethane (PU) that can be electrospun for use as a scaffold in soft tissue engineering. The PU was synthesized from polycaprolactone diol, hexamethylene diisocyanate, and dimethylolpropionic acid (DMPA) chain extender using two-step polymerization and designated as PU-DMPA. A control PU using 1,4-butanediol (1,4-BDO) as a chain extender was synthesized similarly and designated as PU-BDO. The chemical structure of the two PUs was verified by FT-IR and 1H-NMR. The PU-DMPA had a lower molecular weight than the PU-BDO (~16,700 Da vs. ~78,600 Da). The melting enthalpy of the PU-DMPA was greater than that of the PU-BDO. Both the PUs exhibited elastomeric behaviors with a comparable elongation at break (λ=L/L0= 13.2). The PU-DMPA had a higher initial modulus (19.8 MPa vs. 8.7 MPa) and a lower linear modulus (0.7 MPa vs. 1.2 MPa) and ultimate strength (9.5 MPa vs. 13.8 MPa) than the PU-BDO. The PU-DMPA had better hydrophilicity than the PU-BDO. Both the PUs displayed no cytotoxicity, although the adhesion of human umbilical artery smooth muscle cells on the PU-DMPA surface was better. Bead free electrospun PU-DMPA membranes with a narrow fiber diameter distribution were successfully fabricated. As a demonstration of its functionalizability, gelatin was conjugated to the electrospun PU-DMPA membrane using carbodiimide chemistry. Moreover, hyaluronic acid was immobilized on the amino-functionalized PU-DMPA. In conclusion, the PU-DMPA has the potential to be used as a scaffold material for soft tissue engineering.

Polypeptide Composition and Topology Affect Hydrogelation of Star-Shaped Poly(L-lysine)-Based Amphiphilic Copolypeptides.

In this research, we studied the effect of polypeptide composition and topology on the hydrogelation of star-shaped block copolypeptides based on hydrophilic, coil poly(L-lysine)20 (s-PLL20) tethered with a hydrophobic, sheet-like polypeptide segment, which is poly(L-phenylalanine) (PPhe), poly(L-leucine) (PLeu), poly(L-valine) (PVal) or poly(L-alanine) (PAla) with a degree of polymerization (DP) about 5. We found that the PPhe, PLeu, and PVal segments are good hydrogelators to promote hydrogelation. The hydrogelation and hydrogel mechanical properties depend on the arm number and hydrophobic polypeptide segment, which are dictated by the amphiphilic balance between polypeptide blocks and the hydrophobic interactions/hydrogen bonding exerted by the hydrophobic polypeptide segment. The star-shaped topology could facilitate their hydrogelation due to the branching chains serving as multiple interacting depots between hydrophobic polypeptide segments. The 6-armed diblock copolypeptides have better hydrogelation ability than 3-armed ones and s-PLL-b-PPhe exhibits better hydrogelation ability than s-PLL-b-PVal and s-PLL-b-PLeu due to the additional cation-π and π-π interactions. This study highlights that polypeptide composition and topology could be additional parameters to manipulate polypeptide hydrogelation.

Removal of an abluminal lining improves decellularization of human umbilical arteries.

The decellularization of long segments of tubular tissues such as blood vessels may be improved by perfusing decellularization solution into their lumen. Particularly, transmural flow that may be introduced by the perfusion, if any, is beneficial to removing immunogenic cellular components in the vessel wall. When human umbilical arteries (HUAs) were perfused at a transmural pressure, however, very little transmural flow was observed. We hypothesized that a watertight lining at the abluminal surface of HUAs hampered the transmural flow and tested the hypothesis by subjecting the abluminal surface to enzyme digestion. Specifically, a highly viscous collagenase solution was applied onto the surface, thereby restricting the digestion to the surface. The localized digestion resulted in a water-permeable vessel without damaging the vessel wall. The presence of the abluminal lining and its successful removal were also supported by evidence from SEM, TEM, and mechanical testing. The collagenase-treated HUAs were decellularized with 1% sodium dodecyl sulfate (SDS) solution under either rotary agitation, simple perfusion, or pressurized perfusion. Regardless of decellularization conditions, the decellularization of HUAs was significantly enhanced after the abluminal lining removal. Particularly, complete removal of DNA was accomplished in 24 h by pressurized perfusion of the SDS solution. We conclude that the removal of the abluminal lining can improve the perfusion-assisted decellularization.

Antibacterial polypeptide/heparin composite hydrogels carrying growth factor for wound healing.

We report an efficient growth factor delivering system based on polypeptide/heparin composite hydrogels for wound healing application. Linear and star-shaped poly(l-lysine) (l-PLL and s-PLL) were chosen due to not only their cationic characteristics, facilitating the efficient complexation of negatively charged heparin, but also the ease to tune the physical and mechanical properties of as-prepared hydrogels simply by varying polypeptide topology and chain length. The results showed that polymer topology can be an additional parameter to tune hydrogel properties. Our experimental data showed that these composite hydrogels exhibited low hemolytic activity and good cell compatibility as well as excellent antibacterial activity, making them ideal as wound dressing materials. Unlike other heparin-based hydrogels, these composite hydrogels with heparin densely deposited on the surface can increase the stabilization and concentration of growth factor, which can facilitate the healing process as confirmed by our in vivo animal model. We believe that these PLL/heparin composite hydrogels are promising wound dressing materials and may have potential applications in other biomedical fields.

Transforming growth factor-beta signaling in hypertensive remodeling of porcine aorta.

A porcine aortic coarctation model was used to examine regulation of gene expression in early hypertensive vascular remodeling. Aortic segments were collected proximal (high pressure) and distal (low pressure) to the coarctation after 2 wk of sustained hypertension (mean arterial pressure>150 mmHg). Porcine 10K oligoarrays used for gene expression profiling of the two regions of aorta revealed downregulation of cytoskeletal and upregulation of extracellular region genes relative to the whole genome. A genomic database search for transforming growth factor-beta (TGF-beta) control elements showed that 19% of the genes that changed expression due to hypertension contained putative TGF-beta control elements. Real-time RT-PCR and microarray analysis showed no change in expression of TGF-beta1, TGF-beta2, TGF-beta3, or bone morphogenetic proteins-2 and -4, yet immunohistochemical staining for phosphorylated SMAD2, an indicator of TGF-beta signaling, and for phosphorylated SMAD1/5/8, an indicator of signaling through the bone morphogenetic proteins, showed the highest percentage of positively stained cells in the proximal aortic segments of occluded animals. For TGF-beta signaling, this increase was significantly different than for sham-operated controls. Western blot analysis showed no difference in total TGF-beta1 protein levels with respect to treatment or aortic segment. Immunohistochemistry showed that the protein levels of latency-associated peptide was decreased in proximal segments of occluded animals. Collectively, these results suggest that activation of TGF-beta, but not altered expression, may be a major mechanism regulating early hypertensive vascular remodeling.

Use of Aligned Microscale Sacrificial Fibers in Creating Biomimetic, Anisotropic Poly(glycerol sebacate) Scaffolds.

Poly(glycerol sebacate) (PGS) is a biocompatible, biodegradable elastomer that has been shown promise as a scaffolding material for tissue engineering; it is still challenging, however, to produce anisotropic scaffolds by using a thermoset polymer, such as PGS. Previously, we have used aligned sacrificial poly(vinyl alcohol) (PVA) fibers to help produce an anisotropic PGS membrane; a composite membrane, formed by embedding aligned PVA fibers in PGS prepolymer, was subjected to curing and subsequent PVA removal, resulting in aligned grooves and cylindrical pores on the surface of and within the membrane, respectively. PVA, however, appeared to react with PGS during its curing, altering the mechanical characteristics of PGS. In this study, aligned sacrificial fibers made of polylactide (PLA) were used instead. Specifically, PLA was blend-electrospun with polyethylene oxide to increase the sacrificial fiber diameter, which in turn increased the size of the grooves and cylindrical pores. The resultant PGS membrane was shown to be in vitro cyto-compatible and mechanically anisotropic. The membrane's Young's modulus was 1-2 MPa, similar to many soft tissues. In particular, the microscale grooves on the membrane surface were found to be capable of directing cell alignment. Finally, based on the same approach, we fabricated a biomimetic, anisotropic, PGS tubular scaffold. The compliance of the tubular scaffold was comparable to native arteries and in the range of 2% to 8% per 100 mmHg, depending on the orientations of the sacrificial fibers. The anisotropic PGS tubular scaffolds can potentially be used in vascular tissue engineering.

Preparation of aligned poly(glycerol sebacate) fibrous membranes for anisotropic tissue engineering.

The use of fibrous scaffolds for tissue repair or regeneration is advantageous for its microstructure similar to that of the native ECM. Aligned fibrous scaffold, in particular, can be used to manipulate cell alignment and hence the microstructure of the resultant tissue. In our previous study, nanofibers consisting of solely poly(glycerol sebacate) (PGS) have been successfully fabricated using core-shell coaxial electrospinning followed by curing and subsequent shell removal. When we tried to fabricate aligned PGS fibrous membranes by collecting the electrospun fibers on a rapidly rotating drum, however, loss of fibrous structure was observed upon curing. This might be due to the broken fibers that were collected under tension; the core PGS prepolymer that melts at high temperature could leak from the broken ends during curing. In this study, attempts were made to reduce the possibility of the fiber breakage. At each stage of preparation, fiber morphology was examined by SEM and fiber compositions were verified by Fourier transform infrared spectroscopy and differential scanning calorimetry. Mechanical properties of the aligned PGS fibrous membrane were evaluated by uniaxial tensile testing both in parallel and perpendicular to the principal fiber direction. SEM images showed that fibrous morphology was better preserved upon the adjustment of the shell composition and the rotational speed of the collector drum. The final PGS fibers remained to be aligned although the alignment was less strong than that of as-spun core-shell fibers. The aligned PGS fibrous membrane exhibited anisotropic mechanical properties with Young's modulus in parallel and perpendicular to the principal fiber direction being 0.98 ±â€¯0.04 MPa and 0.52 ±â€¯0.02 MPa, respectively. The aligned PGS fibrous membrane was capable of guiding the orientation of cultured cells and therefore has the potential to be used to fabricate structurally anisotropic tissue-engineered constructs.

Combination of inductive effect of lipopolysaccharide and in situ mechanical conditioning for forming an autologous vascular graft in vivo.

Autologous vascular grafts have the advantages of better biocompatibility and prognosis. However, previous studies that implanted bare polymer tubes in animals to grow autologous tubular tissues were limited by their poor yield rates and stability. To enhance the yield rate of the tubular tissue, we employed a design with the addition of overlaid autologous whole blood scaffold containing lipopolysaccharides (LPS). Furthermore, we applied in vivo dynamic mechanical stimuli through cyclically inflatable silicone tube to improve the mechanical properties of the harvested tissues. The effectiveness of the modification was examined by implanting the tubes in the peritoneal cavity of rats. A group without mechanical stimuli served as the controls. After 24 days of culture including 16 days of cyclic mechanical stimuli, we harvested the tubular tissue forming on the silicone tube for analysis or further autologous interposition vascular grafting. In comparison with those without cyclic dynamic stimuli, tubular tissues with this treatment during in vivo culture had stronger mechanical properties, better smooth muscle differentiation, and more collagen and elastin expression by the end of incubation period in the peritoneal cavity. The grafts remained patent after 4 months of implantation and showed the presence of endothelial and smooth muscle cells. This model shows a new prospect for vascular tissue engineering.

Time courses of growth and remodeling of porcine aortic media during hypertension: a quantitative immunohistochemical examination.

Arteries undergo marked structural and functional changes in human and experimental hypertension that generally involve smooth muscle cell (SMC) hypertrophy/hyperplasia as well as abnormal extracellular matrix turnover. In this study we examined time courses of changes in SMC activity and matrix protein content in a novel mini-pig aortic coarctation model. Cell proliferation was evaluated by immunostaining of Ki-67, apoptosis was assessed by TUNEL, and phenotypic changes were monitored by immunostaining three SMC contractile markers (caldesmon, calponin, and smoothelin). Changes in medial collagen and elastin were examined by picrosirius red and Verhoeff-van Gieson staining, respectively. LabVIEW-based image analysis routines were developed to objectively and efficiently quantify the (immuno)histochemical results. We found that significant cell proliferation and matrix production occurred in the early stages of this coarctation model and then declined gradually; the SMCs also tended to exhibit a less contractile phenotype following these cellular and extracellular changes. Specifically, different aspects of the phenotypic changes associated with hypertension occurred at different rates: cell proliferation and collagen production occurred early and peaked by 2 weeks, whereas changes in contractile protein expression continued to decrease over the entire 8-week study period. Temporal changes found in this study emphasize the importance of simultaneously tracing time courses of SMC growth and differentiation as well as matrix protein production and content. SMCs are multifunctional, and caution must be used to not overdefine phenotype. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

Comparison of Mechanical Stability of Elastic Titanium, Nickel-Titanium, and Stainless Steel Nails Used in the Fixation of Diaphyseal Long Bone Fractures.

Elastic nails made of the nickel-titanium shape memory alloy (Nitinol) have been reported to control bone modeling in animal studies. However, the mechanical stability of the Nitinol nail in the fixation of long bone fractures remains unclear. This study compared mechanical stability among nails made of three materials, namely Nitinol, titanium, and stainless steel, in the fixation of long bone fractures. These three materials had identical shapes (arc length: π/2 and radius: 260 mm). A cylindrical sawbone with a 10-mm gap and fixed with two C-shaped elastic nails was used to examine the stability of the nails. A finite element (FE) model was developed based on the sawbone model. The end cap for elastic nails was not used in the sawbone test but was considered based on a constraint equation in FE simulation. The results of stability tests appeared to depend on the presence or absence of the end cap. In the sawbone test, the titanium nail yielded a higher ultimate force against the applied load than did the stainless steel and Nitinol nails before the gap completely closed; the difference in linear stiffness between the nails was nonsignificant. In FE simulation, the titanium nail produced smaller gap shortening than did stainless steel and Nitinol nails without the end cap; the difference in gap shortening between the nails was minor with the end cap. The titanium elastic nail should be a better choice in managing diaphyseal long bone fractures when the end cap is not used. For Nitinol and stainless steel nails, the end cap should be used to stop the nail from dropping out and to stabilize the fractured bone.

Fibroblast-seeded collagen gels in response to dynamic equibiaxial mechanical stimuli: A biomechanical study.

The remodeling of fibroblast-seeded collagen gels in response to dynamic mechanical stimuli was investigated by using a newly developed biaxial culture system capable of cyclically stretching planar soft tissues. Fibroblast-seeded collagen gels were subjected to three distinct dynamic mechanical conditions for six days: Cyclic Equibiaxial Stretching at two constant strain magnitudes (CES-7% and CES-20%), and Cyclic Equibiaxial Stretching with incrementally Increasing stain magnitude (ICES, 7% → 15% → 20% each for two days). The frequency of cyclic stretching was set at 1 Hz. At the end of culture, mechanical properties of the gels were examined by biaxial mechanical testing and checked again upon the removal of seeded cells. Collagen microstructure within the gels was illustrated by multiphoton microscopy. The mRNA levels of collagen type I and type III and fibronectin in the cells were examined by reverse transcription PCR. The protein expression of α-smooth muscle actin was detected by immunohistochemistry. We found that the gels cultured under cyclic stretching were stiffer than those cultured under static stretching. Particularly, the stiffness appeared to be significantly enhanced when the ICES was employed. The enhancement of mechanical properties by cyclic stretching appeared to persist upon cell removal, suggesting an irreversible remodeling of extracellular matrix. Second harmonic generation images showed that collagen fibers became thicker and more compact in the gels cultured under cyclic stretching, which may explain the mechanical findings. The mRNA expression of collagen type I in the cells of the ICES was significantly greater than that of the other groups except for the CES-20%. This study suggests that when cyclic stretching is to be used in engineering soft tissues, incrementally increasing strain magnitude may prove useful in the development of the tissue.