A comparison of both DENSE and feature tracking techniques with tagging for the cardiovascular magnetic resonance assessment of myocardial strain.

BACKGROUND: Myocardial strain is increasingly recognized as an important assessment for myocardial function. In addition, it also improves outcome prediction. However, there is lack of standardization in strain evaluation by cardiovascular magnetic resonance (CMR). In this study we compared strain values using multiple techniques and multiple vendor products. METHODS: Prospectively recruited patients with cardiomyopathy of diverse etiology (N = 77) and healthy controls (N = 10) underwent CMR on a 1.5 T scanner. Tagging, displacement encoding with stimulated echoes (DENSE) and balanced stead state free precession cine imaging were acquired on all subjects. A single matched mid left ventricular (LV) short axis plane was used for the comparisons of peak circumferential (Ecc) and radial strain (Err) and a 4-chamber view for longitudinal strain (Ell). Tagging images were analyzed using harmonic phase (HARP) and displacement encoding with stimulated echoes (DENSE) images using a proprietary program. Feature tracking (FT) was evaluated using 3 commercially available software from Tomtec Imaging Systems, Cardiac Image Modeller (CIM), and Circle Cardiovascular Imaging. Tagging data were used as reference. Statistic analyses were performed using paired t-test, intraclass correlation coefficient (ICC), Bland Altman limits of agreement and coefficient of variations. RESULTS: Average LV ejection fraction was 50% (range 32 to 62%). Regional LV wall motion abnormalities were present in 48% of the analyzed planes. The average Ecc was - 13 ± 4%, - 13 ± 4%, - 16 ± 6%, - 10 ± 3% and - 14 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively, with the best agreement seen in DENSE and Circle with tagging. The Err was highly varied with poor agreement across the techniques, 32 ± 24%, 40 ± 28%, 47 ± 26%, 64 ± 33% and 23 ± 9% for tagging, DENSE, Tomtec, CIM and Circle, respectively. The average Ell was - 14 ± 4%, - 8 ± 3%, - 13 ± 5%, - 11 ± 3% and - 12 ± 4% for tagging, DENSE, Tomtec, CIM and Circle, respectively with the best agreement seen in Tomtec and Circle with tagging. In the intra- and inter-observer agreement analysis the reproducibility of each technique was good except for Err by HARP. CONCLUSIONS: Small but important differences are evident in Ecc and Ell comparisons among vendors while large differences are seen in Err assessment. Our findings suggest that CMR strain values are technique and vendor dependent. Hence, it is essential to develop reference standard from each technique and analytical product for clinical use, and to sequentially compare patient data using the same software.

Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta.

Adventitial fibroblasts (AFs) can be activated by angiotensin II (Ang II) and exert pro-fibrotic and pro-inflammatory effects in vascular remodeling. Protease-activated receptor (PAR) 1 and 2 play a significant role in fibrogenic and inflammatory diseases. The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling. We found that direct activation of PAR1 and PAR2 with PAR1-AP and PAR2-AP led to AF activation, including proliferation and differentiation of AFs, extracellular matrix synthesis, as well as production of pro-fibrotic cytokine TGF-ß and pro-inflammatory cytokines IL-6 and MCP-1. Furthermore, PAR1 and PAR2 mediated Ang II-induced AF activation, since both PAR1 and PAR2 antagonists inhibited Ang II-induced proliferation, migration, differentiation, extracellular matrix synthesis and production of pro-fibrotic and pro-inflammatory cytokines in AFs. Finally, mechanistic study showed that Ang II, via Ang II type I receptor (AT1R), upregulated both PAR1 and PAR2 expression, and transactivated PAR1 and PAR2, as denoted by internalization of both proteins. In conclusion, our results suggest that PAR1 and PAR2 play a critical role in Ang II-induced AF activation, and this may contribute to adventitia-related pathological changes.

Poly(ethylene glycol)-modified PAMAM-Fe3O4-doxorubicin triads with the potential for improved therapeutic efficacy: generation-dependent increased drug loading and retention at neutral pH and increased release at acidic pH.

Polyamidoamine (PAMAM) dendrimer-coated magnetic nanoparticles are a promising drug-delivery system that can enhance the therapeutic effects of chemotherapy drugs, such as doxorubicin (DOX), with minimized side effects. This work explores the optimization of the potential therapeutic efficiency of PAMAM-Fe3O4-DOX triads. Different generations (G3, G5, and G6) of PAMAMs were synthesized and modified with poly(ethylene glycol) (PEG) and then used to encapsulate glutamic acid-modified Fe3O4 nanoparticles. The Fe3O4-dendrimer carriers (Fe3O4-DGx where x = the generation 3, 5, or 6 of dendrimers) were electrostatically conjugated with drug DOX. The loading and releasing efficiencies of DOX increased with the PAMAM generation from 3 to 6. The loading efficiencies of DOX molecules were 87, 93, and 96% for generations 3, 5, and 6, respectively. At pH 5, the DOX release efficiencies within 24 h were approximately 60, 68, and 80% for generations 3, 5, and 6, respectively. At pH 7.4, the DOX releasing efficiency was as low as ∼ 15%. Compared to the negative control, the PAMAM-Fe3O4-DOX triads showed only mild toxicity against human cervical adenocarcinoma cell line HeLa at pH 7.4, which indicated that DOX can be fairly benignly carried and sparingly released until PAMAM-Fe3O4-DOX is taken up into the cell.

Low paraoxonase 1 arylesterase activity and high von Willebrand factor levels are associated with severe coronary atherosclerosis in patients with non-diabetic stable coronary artery disease.

BACKGROUND: Paraoxonase 1 (PON1) activity and von Willebrand factor (VWF) release are associated with lesion initiation in atherosclerosis. Diabetes can complicate coronary artery disease (CAD) due to the production of advanced glycation end products. This study evaluated PON1 activity and VWF levels in non-post-acute coronary syndrome, stable CAD (SCAD) patients without diabetes. MATERIAL/METHODS: Non-diabetic SCAD patients and patients experiencing acute stress periods were selected (n=130). Forty-seven cases with normal coronary angiography and 50 healthy individuals served as controls. The non-diabetic SCAD group was then stratified into single-vessel lesions, multiple-vessel lesions, and mild or severe luminal stenosis according to the number and the degree of luminal stenoses. Serum PON1 paraoxonase and arylesterase activities, and plasma VWF levels were measured, as well as serum total cholesterol, total triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A1. PON1 arylesterase activity was detected with an ordinary chemistry system using a novel phenylacetate derivative. RESULTS: Both PON1 paraoxonase and arylesterase were lower in the non-diabetic SCAD group, but VWF levels were higher (versus controls, all P<0.001). PON1 paraoxonase activity (OR=0.991), PON1 arylesterase activity (OR=0.981), and VWF (OR 2.854) influenced SCAD in multiple logistic regression. Decreased PON1 arylesterase activity and increased VWF levels were associated with severe atherosclerosis in non-diabetic SCAD patients. We also observed a slight negative correlation between VWF and PON1 paraoxonase/arylesterase. CONCLUSIONS: PON1 and VWF are detectable markers that may predict the severity of stenoses, ideally facilitating a non-diabetic SCAD diagnosis before the sudden onset of life-threatening symptoms.

A chemical coating strategy for assembling a boron-doped diamond anode towards electrocatalytic degradation of late landfill leachate.

The high efficiency electrocatalytic degradation of late landfill leachate is still not an easy task due to the complexity and variability of organic pollutants. A chemical coating strategy for assembling a boron-doped diamond anode (BDD) towards electrocatalytic degradation of late landfill leachate was adopted and studied. The results shows the high removal rates of organic carbon (TOC) and ammonia nitrogen (NH3-N) after electrochemical oxidation for 5 h can reach 99% and 100%. Further, the organic migration and transformation depends on current density, A/V value, initial pH, electrochemical degradation time, and composition of the stock solution. Specifically, alkaline conditions can increase both TOC and NH3-N removal rates, which is reflected in the NH3-N removal rate of 100% when the pH is 8.5 after only 5 h. The types of organic matter decreased from 63 species to 24 species in 5 h, in which the removal of fulvic acids is superior to that of soluble biometabolites. Amides/olefins and phenolic alcohols are all degraded and converted into other substances or decomposed into CO2 and H2O by BDD, accompanied by the continuous decomposition of alcohol-phenols into alkanes. In all, this study provides a core reference on electrocatalytic degradation of late landfill leachate.

Microbially mediated sulfur oxidation coupled with arsenate reduction within oligotrophic mining-impacted habitats.

Arsenate reduction is a major cause of As release from soils which threatens more than 200 million people worldwide. While heterotrophic As(V) reduction has been investigated extensively, the mechanism of chemolithotrophic As(V) reduction is less studied. Since As is frequently found as sulfidic minerals in the environment, microbial mediated sulfur oxidation coupled to As(V) reduction (SOAsR), a chemolithotrophic process, may be more favorable in oligotrophic mining-impacted sites (e.g., As-contaminated mine tailings). While SOAsR is thermodynamically favorable, knowledge regarding this biogeochemical process is still limited. The current study suggested that SOAsR was a more prevalent process compared to heterotrophic As(V) reduction in oligotrophic sites, such as mine tailings. The water-soluble reduced sulfur concentration was predicted as one of the major geochemical parameters that substantially impacted SOAsR potentials. A combination of DNA-SIP and metagenome binning revealed members of the genera Sulfuricella, Ramlibacter, and Sulfuritalea as sulfur oxidizing As(V)-reducing bacteria (SOAsRB) in mine tailings. Genome mining further expanded the list of potential SOAsRBs to diverse phylogenetic lineages such as members associated with Burkholderiaceae and Rhodocyclaceae. Metagenome analysis using multiple tailing samples across southern China confirmed that the putative SOAsRB were the dominant As(V) reducers in these sites. Together, the current findings expand our knowledge regarding the chemolithotrophic As(V) reduction process, which may be harnessed to facilitate future remediation practices in mine tailings.

The relationships between cholesterol crystals, NLRP3 inflammasome, and coronary atherosclerotic plaque vulnerability in acute coronary syndrome: An optical coherence tomography study.

Background: Cholesterol crystals (CCs) in lesions are the hallmark of advanced atherosclerotic plaque. Previous studies have demonstrated that CCs could activate NLRP3 inflammasome, which played an important role in atherosclerotic lesion progression. However, the relationship between CCs, NLRP3 inflammasome pathway, and plaque vulnerability in patients with ACS is still not elucidated. Methods: Two hundred sixty-nine consecutive acute coronary syndrome (ACS) patients with 269 culprit lesions were included in this study. CCs and other plaque characteristics within the culprit lesion segment were evaluated by optical coherence tomography (OCT) before percutaneous coronary intervention (PCI). The NLRP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and the serum levels of interleukin (IL)-1ß, IL-18, and other biological indices were measured. Results: Cholesterol crystals were observed in 105 (39%) patients with 105 culprit lesions. There were no significant differences in baseline clinical characteristics between the patients with CCs (CCs group, n = 105) and the patients without CCs (non-CCs group, n = 164) within the culprit lesion segment except for lipoprotein(a) [Lp(a)]. The CCs group had a higher level of NLRP3 mRNA expression in PBMCs and higher levels of serum cytokine IL-1ß and IL-18. OCT showed that the CCs group had longer lesion length, more severe diameter stenosis, and less minimum luminal area (MLA) than the non-CCs group (all p < 0.05). The frequency of thin-cap fibroatheroma (TCFA), thrombus, accumulation of macrophages, plaque rupture, micro-channel, calcification, spotty calcification, and layered plaque was higher in the CCs group than in the non-CCs groups (all p < 0.05). Multivariate logistic analysis revealed that the level of NLRP3 expression (OR = 10.204), IL-1ß levels (OR = 3.523), IL-18 levels (OR = 1.006), TCFA (OR = 3.593), layered plaque (OR = 5.287), MLA (OR = 1.475), macrophage accumulation (OR = 2.881), and micro-channel (OR = 3.185) were independently associated with CCs. Conclusion: Acute coronary syndrome patients with CCs in culprit lesions had a higher expression of NLRP3, IL-1ß, and IL-18, and had more vulnerable plaque characteristics than patients without CCs. CCs might have interacted with NLRP3 inflammasome activation in patients with ACS, which could contribute to plaque vulnerability in culprit lesions.

Perivascular adipose tissue-derived complement 3 is required for adventitial fibroblast functions and adventitial remodeling in deoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVE: To examine the role of perivascular adipose tissue (PVAT)-derived factors in the regulation of adventitial fibroblast (AF) function in vitro and in vivo. METHODS AND RESULTS: PVAT is an active component of blood vessels. Bioactive substances released from PVAT play regulatory roles in vascular function. However, their effects on vascular AFs remain unclear. PVAT-conditioned medium stimulated AF migration using a transwell technique, and differentiation was evaluated by α-smooth muscle-actin induction. We identified the secretome of PVAT by liquid chromatography-tandem mass spectrometry. One of the major secretory proteins in PVAT is complement 3 (C3). The C3 antagonist and neutralizing antibody attenuated PVAT-conditioned medium-induced AF migration and differentiation. Similar to PVAT-conditioned medium, C3 recombinant protein stimulated AF migration and differentiation. We demonstrated that the effects of PVAT-derived C3 were mediated by the c-Jun N-terminal kinase pathway. Moreover, we found morphological changes in perivascular adipocytes and increased expression of C3 in PVAT that was tightly associated with adventitial thickening and myofibroblast clustering around PVAT in deoxycorticosterone acetate-salt hypertensive rats. CONCLUSIONS: PVAT-derived C3 stimulated AF migration and differentiation via the c-Jun N-terminal kinase pathway. PVAT-derived C3 may contribute to adventitial remodeling in a deoxycorticosterone acetate-salt hypertensive model.

Ce regulated surface properties of Mn/SAPO-34 for improved NH3-SCR at low temperature.

Ce modified MnO x /SAPO-34 was prepared and investigated for low-temperature selective catalytic reduction of NO x with ammonia (NH3-SCR). The 0.3Ce-Mn/SAPO-34 catalyst had nearly 95% NO conversion at 200-350 °C at a space velocity of 10 000 h-1. Microporous SAPO-34 as the support provided the catalyst with increased hydrothermal stability. XPS and H2-TPR results proved that the Mn4+ and Oα content increased after incorporation of Ce, this promoted the conversion of NO at low temperature via a 'fast SCR' route. NH3-TPD measurements combined oxidation experiments of NO, NH3 indicated the reduction of both the surface acidity and the amount of acid sites, which effectively decreased the NH3 oxditaion to NO or N2O at elevated temperature and promoted the catalytic selectivity for nitrogen. A redox cycle between manganese oxide and Ce was assumed for the active oxygen transfer and facilitated the catalyst durability.

Overexpression of CXCR1/CXCR2 on mesenchymal stromal cells may be an effective treatment for acute myocardial infarction.

Bone marrow (BM)-derived mesenchymal stromal cells (MSC) participate in myocardial repair following myocardial infarction (MI). However, their reparative capability is limited, partly because of poor homing abilities. MI is associated with an inflammatory reaction. Interleukin-8 (IL-8) appears to have a fundamental role in regulating neutrophil localization in ischemic tissues through binding CXCR1/CXCR2 receptors, which show major expression on neutrophils. We hypothesize that the application of IL-8 will enhance the recruitment of overexpressing CXCR1/CXCR2 MSC to sites of degenerated tissue of myocardium, decreasing the ischemic region and improving cardiac function.

Proteinase­activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury.

Previous studies have established that proteinase­â€‹activated receptor 2 (PAR2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferase­mediated dUTP nick end­labeling staining. Annexin V/propidium iodide staining, and expression of Bcl­2 and cleaved PARP were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injury­simulating MI/RI. Phosphorylated ERK1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR2 knockdown clearly prevented phosphorylation of ERK1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RI­associated apoptosis by inhibiting phosphorylation of ERK1/2 and JNK. Therefore, targeted PAR2 silencing may be a potential therapeutic approach for alleviation of MI/RI.

Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue.

The myocardial tissue lacks significant intrinsic regenerative capability to replace the lost cells. Therefore, the heart is a major target of research within the field of tissue engineering, which aims to replace infarcted myocardium and enhance cardiac function. The primary objective of this work was to develop a biocompatible, degradable and superelastic heart patch from poly(glycerol sebacate) (PGS). PGS was synthesised at 110, 120 and 130 degrees C by polycondensation of glycerol and sebacic acid with a mole ratio of 1:1. The investigation was focused on the mechanical and biodegrading behaviours of the developed PGS. PGS materials synthesised at 110, 120 and 130 degrees C have Young's moduli of 0.056, 0.22 and 1.2 MPa, respectively, which satisfy the mechanical requirements on the materials applied for the heart patch and 3D myocardial tissue engineering construction. Degradation assessment in phosphate buffered saline and Knockout DMEM culture medium has demonstrated that the PGS has a wide range of degradability, from being degradable in a couple of weeks to being nearly inert. The matching of physical characteristics to those of the heart, the ability to fine tune degradation rates in biologically relevant media and initial data showing biocompatibility indicate that this material has promise for cardiac tissue engineering applications.

Surface functionalization of Bioglass-derived porous scaffolds.

Like standard tissue culture plates, tissue engineering scaffolds can be chemically treated to couple proteins without losing the conformation and thus biological function of the proteins; a process called surface functionalization. In this work, the surface of novel 45S5 Bioglass-derived foam-like scaffolds, which exhibit adequate mechanical stability and tailorable bioresorbability, have been modified by applying 3-aminopropyl-triethoxysilane. The efficiency and stability of the surface modification were satisfactorily and quantitatively assessed by X-ray photoemission spectroscopy. It was also found that treatment in buffered (pH 8) water solution at 80 degrees C for 4h, applied during the surface functionalization procedure, accelerated the bioreactive kinetics of the scaffolds, i.e. the transition of the relatively bioinert but mechanically competent crystalline structure of the struts to a biodegradable but mechanically weak amorphous network during immersion in simulated body fluid. Thus the aqueous heat treatment is confirmed to be an important factor that must be considered in the design of these Bioglass-derived glass-ceramic scaffolds. Possible mechanisms responsible for the accelerated bioreactivity are proposed.

45S5 Bioglass-derived glass-ceramic scaffolds for bone tissue engineering.

Three-dimensional (3D), highly porous, mechanically competent, bioactive and biodegradable scaffolds have been fabricated for the first time by the replication technique using 45S5 Bioglass powder. Under an optimum sintering condition (1000 degrees C/1h), nearly full densification of the foam struts occurred and fine crystals of Na2Ca2Si3O9 formed, which conferred the scaffolds the highest possible compressive and flexural strength for this foam structure. Important findings are that the mechanically strong crystalline phase Na2Ca2Si3O9 can transform into an amorphous calcium phosphate phase after immersion in simulated body fluid for 28 days, and that the transformation kinetics can be tailored through controlling the crystallinity of the sintered 45S5 Bioglass. Therefore, the goal of an ideal scaffold that provides good mechanical support temporarily while maintaining bioactivity, and that can biodegrade at later stages at a tailorable rate is achievable with the developed Bioglass-based scaffolds.

Long-term prescription of beta-blocker delays the progression of heart failure with preserved ejection fraction in patients with hypertension: A retrospective observational cohort study.

BACKGROUND: Hypertension complicated with left ventricular hypertrophy (LVH) and diastolic dysfunction is one of the most common risks for heart failure with preserved ejection fraction (HFpEF). This study was designed to evaluate the influences of long-term beta-blocker prescription in these patients. METHODS: This retrospective analysis included eligible patients diagnosed with hypertension, LVH (left ventricular (LV) mass index >125 g/m(2) for men and >110 g/m(2) for women) and suspected diastolic dysfunction (E/E' ratio between 8 and 15) and without clinical signs or symptoms of heart failure in our hospital medical record database (January 2005-December 2009). A total of eligible 1498 patients were enrolled, of whom 803 received beta-blocker prescription and 695 accepted non-beta-blocker therapy. RESULTS: With a median follow-up of 7.2 years, the new-onset symptomatic HFpEF occurred in 48 of 803 patients in the beta-blocker group (6.0%) and 92 of 695 patients in the non-beta-blocker group (13.2%, p < 0.001). Beta-blockers also generated more prominent improvement in diastolic function and LVH. And Cox proportional hazards model revealed that beta-blocker (hazard ratio (HR) 0.327, 95% confidence interval (CI): 0.121-0.540, p = 0.009) or angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) exposure (HR 0.422, 95% CI: 0.210-0.699, p = 0.015) was associated with a reduced risk of new onset of symptomatic HFpEF, and the elevation of LVMI (HR 1.210, 95% CI: 1.069-1.362, p = 0.040) or E/E' (HR 1.398, 95% CI: 1.306-1.541, p = 0.032) was associated with a high risk of new onset of symptomatic HFpEF. CONCLUSIONS: Long-term beta-blocker exposure was associated with protective effects in terms of the incidence of new-onset symptomatic HFpEF, LV diastolic dysfunction and LVH, which might be beneficial for the delay of HFpEF progression.

[Application of SIR model in forecasting and analyzing for SARS].

An SIR epidemic model is applied on the research of SARS. Parameters in the model are estimated and forecasted by two methods. Time-varying estimated parameters are also compared for Beijing and Hong Kong SARS epidemic situations.

Novel elastomeric fibrous networks produced from poly(xylitol sebacate)2:5 by core/shell electrospinning: fabrication and mechanical properties.

Fabrication of nonlinear elastic materials that resemble biological tissues remains a challenge in biomaterials research. Here, a new fabrication protocol to produce elastomeric fibrous scaffolds was established, using the core/shell electrospinning technique. A prepolymer of poly(xylitol sebacate) with a 2:5mol ratio of xylitol:sebacic acid (PXS2:5) was first formulated, then co-electrospun with polyvinyl alcohol (PVA - 95,000Mw). After cross-linking of core polymer PXS2:5, the PVA shells were rinsed off in water, leaving a porous elastomeric network of PXS2:5 fibres. Under aqueous conditions, the PXS2:5 fibrous scaffolds exhibited stable, nonlinear J-shaped stress-strain curves, with large average rupture elongation (76%) and Young׳s modulus (~1.0MPa), which were in the range of muscle tissue. Rupture elongation of PXS2:5 was also much higher when electrospun, compared to 2D solid sheets (45%). In direct contact with cell monolayers under physiological conditions, PXS2:5 scaffolds were as biocompatible as those made of poly-l-lactic acid (PLLA), with improvements over culture medium alone. In conclusion, the newly developed porous PXS2:5 scaffolds show tissue-like mechanical properties and excellent biocompatibility, making them very promising for bioengineering of soft tissues and organs.

Enzymatic and oxidative degradation of poly(polyol sebacate).

Poly(glycerol sebacate) (PGS) and poly(xylitol sebacate) (PXS) are biodegradable elastomers with tremendous potential in soft tissue engineering. This study was aimed at exploring the enzymatic degradation mechanisms of these polyesters, using biochemical conditions similar to those occurring in vivo. To this end, PGS and PXS (crosslinked at 130 for 2 or 7 (PGS)/12 days (PXS)) were incubated in vitro under physiological conditions in tissue culture media supplemented with either a biodegrading enzyme (esterase), an oxidant species (FeSO4/H2O2 with 0.11 molar ratio of Fe(2+/)H2O2), an oxidant generating enzyme (xanthine oxidase and xanthine) or combinations of these (FeSO4/H2O2 and esterase, or (v) xanthine oxidase/xanthine and esterase), based on their independent effects on polymer degradation. Testing was performed over 35 days of continuous incubation, during which mechanical properties, mass loss, biomaterial thickness and pH value of the culture medium were determined. Degradation kinetics of both PGS and PXS samples were primarily determined by the degree of crosslink density. Esterase and FeSO4/H2O2 accelerated the degradation of both polymers, by promoting hydrolysis and free-radical degradation, although this action was not affected by the presence of xanthine oxidase and xanthine. Degradation of PGS and PXS is primarily mediated by the action of esterase, with free-radical oxidation playing a secondary role, suggesting that both could synergistically affect the biodegradability of biomaterial implants, under more complex biological conditions.

Bone tissue engineering scaffolding: computer-aided scaffolding techniques.

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 µm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several µm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.