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

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.

Biomaterials in the development and future of vascular grafts.

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

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.

Purpose: To produce biodurable small diameter microporous vascular grafts with self-sealing properties for vascular access, for peripheral vascular and potentially for coronary artery bypass. The prosthesis should retain compliance and pulsatile flow in situ using a unique modus operandi permitting wall compression which accommodates changes in volume.Method: We have utilised efficient low temperature coagulation technology to develop a unique range of small diameter microporous vascular grafts using ChronoFlex, a biodurable polycarbonate urethane.Results: Grafts have been subjected to a range of in vitro and in vivo testing, demonstrating excellent physical and mechanical characteristics, self-sealing, maintenance of compliance and pulsatile flow in situ and patency up to twenty-two weeks.

Development of a microporous compliant small bore vascular graft.

Degradative cracking, more commonly known as "environmental stress cracking" (ESC) has been observed in many implanted polyetherurethane elastomers. This phenomenon has been attributed to biochemical and cellular interactions at the surface of the implanted material causing polymer chain cleavage. This may result in surface fissuring followed by the deep cracking associated with considerable biodegradation of the polymer, resulting in loss of mechanical strength and the formation of aneurysms in an in vivo situation. These cracking effects are believed to be due to mechanical stress combined with the oxidising actions of macrophages and giant cells, as surface cracking has been observed to occur directly under adherent macrophages on a polyetherurethane implant. These cells form part of the body's immune response which uses enzymes and reactive oxygen species (O2, O2-, and HO. and H2O2) to degrade foreign material. We describe a modification of an in vitro test method developed by Zaho et al. [1] using glass wool and a Hydrogen Peroxide/Cobalt (II) Chloride (H2O2/CoCl2) mixture to replicate the oxidising effects of macrophages in vivo. The modifications were made to establish a routine testing system for resistance to biodegradation which could be used to screen a range of polymers designed for use in microporous vascular grafts. The grafts are pre-stressed by a method devised by Stokes et al. [2] where each graft is stretched to a predetermined elongation over a mandrel and the strain is fixed by tying PTFE tape around each end of the mandrel.

Resistance to Biodegradative Stress Cracking in Microporous Vascular Access Grafts

A comprehensive bio-material investigation of the chemical and thermal stability of a new poly urethane MyoLinK used in the manufacture of cardiovascular grafts to oxidative and hydrolytic stress

Robert J. Carson

Papers

The Mechanical Behavior of Vascular Grafts: A Review

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

Development of a microporous compliant small bore vascular graft.

Resistance to Biodegradative Stress Cracking in Microporous Vascular Access Grafts

A comprehensive bio-material investigation of the chemical and thermal stability of a new poly urethane MyoLinK used in the manufacture of cardiovascular grafts to oxidative and hydrolytic stress