Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - Bi-Stretch-4-Biomed (BIaxial STRETCHing of PLLA-WS2 nanocomposites FOR thinner and stronger BIOMEDical scaffolds)

Teaser

Toward the goal of guiding blood vessels to regenerate into a healthy state after heart disease, our team is creating new materials with the combination of strength, biocompatibility and bioresorption that could revolutionize treatment of coronary heart disease.If successful...

Summary

Toward the goal of guiding blood vessels to regenerate into a healthy state after heart disease, our team is creating new materials with the combination of strength, biocompatibility and bioresorption that could revolutionize treatment of coronary heart disease.
If successful, our research can improve the quality of life of patients, affected by coronary heart disease, who today receive metal stents to hold a clogged artery in an open state. Metal stents allows the patients’ heart to receive nutrients, but at the same time cause chronic chest pain because the rigid metal does not allow the artery to pulse or dilate.  Our research aims to provide the materials needed to restore health rather than simply mitigating symptoms.  That is the idea of a scaffold: a temporary device that guides tissue regeneration and then is resorbed by the body to eliminate long-term complications.
Our objectives are 1) to develop new compositions that combine biocompatible inorganic nanomaterials for strength with polymers that have demonstrated success in transient implants, 2) to understand the way the structure in the new materials responds to processes that are used to form the bioresorbable vascular scaffold (BVS), and 3) to guide the unified design of materials and processes to enable thinner scaffolds that are easier for surgeons to implant and provide better outcomes for patients.

Work performed

\"Toward the objective of creating stronger BVS materials by combining nanofillers with poly(L-lactide) (PLLA), experiments at Caltech with ENEA staff evaluated biocompatibility in vitro with two important types of cells relevant to vasculature (endothelial cells that line blood vessel walls and smooth muscle cells). When tungsten disulfide nanotubes are incorporated into PLLA, the material remains well tolerated. This is true in \"\"direct contact\"\" experiments and in experiments that expose cells to medium that has leached constituents of the nanocomposite. These represent significant steps in the preclinical evaluation of biocompatibility. Also toward the objective of creating stronger BVS, ENEA-Caltech collaboration through reciprocal secondments showed that the addition of WS2 nanotubes does accelerate nucleation of crystallization in PLLA and the resulting interactions make the material stronger and more ductile.

Progress toward the objective of understanding the processing-structure-property relationships of new BVS materials has focused on developing methods, initially using PLLA alone as our foundation. All four institutions have contributed significantly. The ENEA-Caltech collaboration created an apparatus that imposes elongation in \"\"tube expansion,\"\" corresponding to an essential step in producing BVS. The instrument is the first of its kind and brings innovative measurement capabilities to see structure development in situ during stretch blow moulding. Exciting results were obtained when the instrument was used for the first time for real-time synchrotron X-ray measurements: deformation proceeds in distinct steps, first dominated by the glassy character of the pre-formed tube and the later stage that is marked by a sudden appearance of oriented crystals. Warwick has established the ability to extrude samples in the form of sheets that are used in the biaxial stretching apparatus at Queens in biaxial extensional measurements. Strong effects of temperature and elongation rate are observed and provide essential input for parameters of the constitutive model that is needed for the next objective.


Led by Queens and Warwick, we are developing computational tools to predict the macroscopic mechanical properties of PLLA-WS2 (constitutive models being developed by Menary at Queen’s) from the molecular and nanoscopic scale (multiscale modelling by Figiel at Warwick). So far our constitutive modelling captures the behavior of PLLA during stretch blow molding and will proceed to incorporate the features due to WS2 nanotubes. Similarly, the multiscale modeling has made progress in two paths: modeling the PLLA alone and modeling the interaction of nanotubes with semicrystalline polymers starting with carbon nanotube in polyethylene terephthalate, for which data is already available to validate the model. Ultimately the two types of models will be linked: the underlying molecular and nanoscopic mechanisms (validated by in situ x-ray measurements) will provide the parameters for a predictive constitutive model (validated by biaxial elongation measurements).
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Final results

Coronary Heart Disease (CHD) is a severe illness that is responsible for 40% of all deaths worldwide. It claims more lives each year than all communicable maternal, neonatal and nutritional disorders combined. More than 2 million people per year die of CHD only in Europe and USA.

Bioresorbable Vascular Scaffolds (BVS) are a revolutionary treatment of CHD respect to metal stents because they are bioresorbed by the body after restoring healthy state of coronary artery eliminating long-term side effects such as late stent thrombosis. Nevertheless, thickness and radio-opacity are two critical aspects that limit the use of the actual BVS. New materials that enable thinner devices with enhanced contrast during the scaffold implantation are strongly demanded by the physicians to mitigate the risks associated with the implantation procedure. Doctors feel high responsibility when inserting a device that is too thick and not visible under X-rays guidance into the tiny, delicate arteries of their patients.

Our Marie Curie RISE team, composed of engineers, chemists, physicists and materials scientists from the EU and USA research centers, is taking these inputs from physicians to improve the current medical devices of PLLA polymer scaffolds used to treat CHD. Our experimental and modelling research activities will enable rational design of materials and processes that give thinner scaffolds that will be much easier to implant. PLLA reinforced by WS2 nanotubes will be as strong as the actual devices but in a thinner profile. The nanotubes could also improve radio-opacity of the scaffolds, which will further facilitate the implant of the scaffold.

Ultimately, we are dedicated to benefit society by giving doctors new materials to treat a wider range of patients and improve clinical outcomes.

Website & more info

More info: http://www.bi-stretch-4-biomed.com.