Stem cells respond to nanoscale surface features, with changes in cell growth and differentiation mediated by alterations in cell adhesion. The interaction of nanotopographical features with integrin receptors in the cells' focal adhesions alters how the cells adhere to materials surfaces, and defines cell fate through changes in both cell biochemistry and cell morphology. In this Review, we discuss how cell adhesions interact with nanotopography, and we provide insight as to how materials scientists can exploit these interactions to direct stem cell fate and to understand how the behaviour of stem cells in their niche can be controlled. We expect knowledge gained from the study of cell-nanotopography interactions to accelerate the development of next-generation stem cell culture materials and implant interfaces, and to fuel discovery of stem cell therapeutics to support regenerative therapies.

Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate

Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases.

Current advances in research and clinical applications of PLGA-based nanotechnology

Background and aim: Covered self-expandable metal stents (EMS) were recently developed to overcome tumour ingrowth in conventional EMS. However, supporting evidence for the efficacy of covered EMS is lacking. Patients and methods: We enrolled 112 patients with unresectable distal biliary malignancies. They were randomly assigned to polyurethane covered (n = 57) or original diamond stent (n = 55). Results: Stent occlusion occurred in eight patients (14%) after a mean of 304 days in the covered group, and in 21 patients (38%) after a mean of 166 days in the uncovered group. The incidence of covered EMS occlusion was significantly lower than that of uncovered EMS (p = 0.0032). The cumulative stent patency of covered stents was significantly higher than that of uncovered stents (p = 0.0066). No tumour ingrowth occurred in the covered group while it was observed in 15 patients in the uncovered group. In subgroup analysis, the cumulative patency of the covered EMS was significantly higher in pancreatic cancer (p = 0.0363) and metastatic lymph nodes (p = 0.0354). There was no significant difference in survival between the two groups. Acute cholecystitis was observed in two of the covered group and in none of the uncovered group. Mild pancreatitis occurred in five of the covered group and in one of the uncovered group. Conclusions: Covered diamond stents successfully prevented tumour ingrowth and were significantly superior to uncovered stents for the treatment of patients with distal malignant biliary obstruction. However, careful attention must be paid to complications specific to covered self-expandable metal stents, such as acute cholecystitis and pancreatitis.

/pdf/a-prospective-randomised-study-of-covered-versus-uncovered-3g32dwl77q.pdf

A prospective randomised study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction

In this review, we compare the reported values of Young's modulus (YM) obtained from indentation and tensile deformations of soft biological tissues. When the method of deformation is ignored, YM values for any given tissue typically span several orders of magnitude. If the method of deformation is considered, then a consistent and less ambiguous result emerges. On average, YM values for soft tissues are consistently lower when obtained by indentation deformations. We discuss the implications and potential impact of this finding.

http://chemotaxis.semmelweis.hu/CHTXhpg/Durotaxis/DT2/McKeeCT_TissueEng_2011.pdf

Indentation versus tensile measurements of Young's modulus for soft biological tissues.

Polymers such as Dacron((R)) and polytetrafluoroethylene (PTFE) have been used in high flow states with relative success but with limited application at lower flow states. Newer polymers with greater compliance, biomimicry, and ability to evolve into hybrid prostheses, suitable as smaller vessels, are now being introduced. In view of the advances in tissue engineering, this makes possible the creation of an ideal off-the-shelf bypass graft. We present a broad overview of the current state of prosthetic bypass grafts. (c) 2005 Wiley Periodicals. Inc.

Current status of prosthetic bypass grafts: a review.

The development of intimal hyperplasia (IH) near the anastomosis of a vascular graft to artery is directly related to changes in the wall shear rate distribution. Mismatch in compliance and diameter at the end-to-end anastomosis of a compliant artery and rigid graft cause shear rate disturbances that may induce intimal hyperplasia and ultimately graft failure. The principal strategy being developed to prevent IH is based on the design and fabrication of compliant synthetic or innovative tissue-engineered grafts with viscoelastic properties that mirror those of the human artery. The goal of this review is to discuss how mechanical properties including compliance mismatch, diameter mismatch, Young's modulus and impedance phase angle affect graft failure due to intimal hyperplasia.

The Mechanical Behavior of Vascular Grafts: A Review

Background: Compliance mismatch between native artery and prosthetic graft used for infrainguinal bypass is implicated in the aetiology of graft failure. The aim was to quantify the elastic properties of a new compliant poly(carbonate)polyurethane (CPU) vascular graft, and to compare the compliance properties of grafts made from CPU, expanded polytetrafluoroethylene (ePTFE), Dacron and human saphenous vein with that of human muscular artery.Methods: A pulsatile flow phantom was used to perfuse vessel and prosthetic graft segments at physiological pulse pressure and flow. Intraluminal pressure was measured using a Millar Mikro-tip catheter transducer and vessel wall motion was determined with duplex ultrasonography using an echo-locked wall-tracking system. Diametrical compliance and a stiffness index were then calculated for each type of conduit over mean pressures ranging from 30 to 100 mmHg by 10-mmHg increments.Results: The compliance values of CPU and artery (mean over the pressure range) were similar (mean(s.d.) 8.1(0.4) and 8.0(5.9) per cent per mmHg x 10(-2) respectively), although the elastic behaviour of artery was anisotropic unlike CPU, which was isotropic. Dacron and ePTFE grafts had lower compliance values (1.8(1.2) and 1.2(0.3)per cent per mmHg x 10(-2) respectively, averaged over the pressure range). In both these cases, compliance and stiffness differed significantly from that of artery over a mean pressure range of 30-90 mmHg. Human saphenous vein exhibited anisotropic behaviour and, although compliant at low pressure (30 mmHg), was markedly incompliant at higher pressures.Conclusion: Compliant polyurethane grafts offer a greater degree of compliance match than either ePTFE or Dacron.

Compliance properties of conduits used in vascular reconstruction.

In vivo biostability of a poly(carbonate-urea)urethane graft.

Poly(ester) urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether) urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H2O2/CoCl2, t-butyl peroxide/CoCl2 (t-but/CoCl2), and glutathione/t-butyl peroxide/CoCl2 (Glut/t-but/CoCl2); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degreesC for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl2, Glut/ t-but/CoCl2, and plasma fractions I-III. Pulse-Tec grafts exposed to the H2O2/CoCl2 mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl2 and Glut/t-but,/CoCl2 showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl2 mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)urethane grafts do. 2001 John Wiley & Sons, Inc.

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

A biocompatible, biodurable polycarbonate polyurethane with internal polysiloxane segments and devices made therefrom.

Alan Edwards

Papers

The Mechanical Behavior of Vascular Grafts: A Review

Compliance properties of conduits used in vascular reconstruction.

In vivo biostability of a poly(carbonate-urea)urethane graft.

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Hydrolytically-and proteolytically-stable polycarbonate polyurethane silicone copolymers