Functionally tailored materials for medical devices : development of a biocompatible shape memory alloy

Medical devices are constructs created to aid patients who suffer from medical problems, such as health problems regarding arteries in the heart, to patients who have been born with congenital absence, or have become an amputee through disease or trauma. Material selection plays an important role when developing these forms of medical devices, as the materials are required to have the mechanical properties to allow the device to operate with its intended function but also be biocompatible to be used in conjunction with human physiology. Through a literature review, this thesis explores materials and their associated mechanics currently used in medical devices and details other possible materials which could be used that could significantly improve the ability of the device. The review will give particular scope to intelligent materials which could be incorporated into medical devices which could potentially allow the device to grow. This thesis will concentrate on alloy configurations to develop an intelligent material called a shape memory alloy. A shape memory alloy is an alloy type which can „remember‟ and return to original shapes when deformed. Through the use of element composition and development procedures used to create the alloy, the alloy could be manipulated to potentially simulate growth by remembering its original grown form when deformed into a smaller collapsed form. A biocompatible shape memory alloy, Ti-7.5Nb-4Mo-1Sn, has been shown to have shape memory alloy properties (superelasticity and shape memory effect) at low temperatures, around room temperature (20-25°C) and is deemed a suitable starting alloy to re-create and adapt by changing the elemental composition - in particular the more beta stabilising elements Nb and Mo - and development protocols used which will change the alloys phase transformation temperatures so the alloys could change crystal structure showing shape memory effect at human body temperature (37°C) which would allow it to grow by expanding when used in conjunction with a medical devices. The results of the thesis show that Nb has the greatest effect on changing the alloys transformation temperatures, with more Nb amounts moving the temperatures into the 30°C range. Mo is shown to make the alloys more superelastic and also move the transformation temperature and the Sn is shown to make the alloy stronger which is required for use in medical devices that are used with human physiology

A peptide derived from α-fetoprotein prevents the growth of estrogen-dependent human breast cancers sensitive and resistant to tamoxifen

An 8-mer peptide (EMTOVNOG) derived from α-fetoprotein was compared with tamoxifen for activity against growth of human breast cancer xenografts implanted in immune-deficient mice. Both peptide and tamoxifen prevented growth of estrogen-receptor-positive MCF-7 and T47D human breast cancer xenografts. A subline of MCF-7, made resistant to tamoxifen by a 6-month exposure to this drug in culture, was found to be resistant to tamoxifen in vivo. Peptide completely prevented the xenograft growth of this tamoxifen-resistant subline of MCF-7. Neither peptide nor tamoxifen was effective in slowing the xenograft growth of the estrogen-receptor-negative MDA-MB-231 human breast cancer. A worrisome side effect of tamoxifen is its hypertrophic effect on the uterus. In this study, tamoxifen was shown to stimulate the growth of the immature mouse uterus in vivo, and the peptide significantly inhibited tamoxifen's uterotrophic effect. The mechanism of action of peptide is different from that of tamoxifen in that the peptide does not interfere with the binding of [(3)H]estradiol to the estrogen receptor. In conclusion, α-fetoprotein-derived peptide appears to be a novel agent that interferes with the growth of tamoxifen-sensitive as well as tamoxifen-resistant estrogen-receptor-positive human breast cancers; it inhibits the uterotrophic side effect of tamoxifen and, thus, it may be useful in combination with or in place of tamoxifen for treatment of estrogen-receptor-positive human breast cancers