Francesca Gervaso

Effects of different stent designs on local hemodynamics in stented arteries

Following the deployment of a coronary stent and disruption of an atheromatous plaque, the deformation of the arterial wall and the presence of the stent struts create a new fluid dynamic field, which can cause an abnormal biological response. In this study 3D computational models were used to analyze the fluid dynamic disturbances induced by the placement of a stent inside a coronary artery. Stents models were first expanded against a simplified arterial plaque, with a solid mechanics analysis, and then subjected to a fluid flow simulation under pulsatile physiological conditions. Spatial and temporal distribution of arterial wall shear stress (WSS) was investigated after the expansion of stents of different designs and different strut thicknesses. Common oscillatory WSS behavior was detected in all stent models. Comparing stent and vessel wall surfaces, maximum WSS values (in the order of 1Pa) were located on the stent surface area. WSS spatial distribution on the vascular wall surface showed decreasing values from the center of the vessel wall portion delimited by the stent struts to the wall regions close to the struts. The hemodynamic effects induced by two different thickness values for the same stent design were investigated, too, and a reduced extension of low WSS region (<0.5Pa) was observed for the model with a thicker strut.

On the effects of different strategies in modelling balloon-expandable stenting by means of finite element method.

In recent years, computational structural analyses have emerged as important tools to investigate the mechanical response of stent placement into arterial walls. Although most coronary stents are expanded by inflating a polymeric balloon, realistic computational balloon models have been introduced only recently. In the present study, the finite element method is applied to simulate three different approaches to evaluate stent-free expansion and stent expansion inside an artery. Three different stent expansion modelling techniques were analysed by: (i) imposing a uniform pressure on the stent internal surface, (ii) a rigid cylindrical surface expanded with displacement control and (iii) modelling a polymeric deformable balloon. The computational results showed differences in the free and confined-stent expansions due to different expansion techniques. The modelling technique of the balloon seems essential to estimate the level of injury caused on arterial walls during stent expansion.

Expansion and drug elution model of a coronary stent

The present study illustrates a possible methodology to investigate drug elution from an expanded coronary stent. Models based on finite element method have been built including the presence of the atherosclerotic plaque, the artery and the coronary stent. These models take into account the mechanical effects of the stent expansion as well as the effect of drug transport from the expanded stent into the arterial wall. Results allow to quantify the stress field in the vascular wall, the tissue prolapse within the stent struts, as well as the drug concentration at any location and time inside the arterial wall, together with several related quantities as the drug dose and the drug residence times.

Assessment of tissue prolapse after balloon-expandable stenting: influence of stent cell geometry.

Restenosis is a re-narrowing or blockage of an artery at the same site where treatment, such as a balloon angioplasty or stent procedure, has already taken place. Several clinical trials have shown a significant reduction in the restenosis rates with endovascular stenting. The purpose of stenting is to maintain the arterial lumen open by a scaffolding action that provides radial support. However, stenting can cause a vascular injury during the deployment. Indeed, in-stent restenosis remains a major problem in percutaneous coronary intervention, requiring patients to undergo repeated procedures and surgery. The loading imposed by the deployment of the stent on the artery is involved in the restenosis process. Furthermore, it is well known that the stent design plays a role in the outcome of the stenting interventional procedure. This study compares the mechanical effects of the expansion of five different designs of balloon-expandable stents in a coronary artery by means of numerical models based on the finite element method. An index for the evaluation of the tissue prolapse based on the expanded configuration reached by the stent cells is proposed. The effects of the balloon inflation and deflation are included in the present study. Wall stresses and tissue prolapse of the vessel wall within the stent cells are evaluated and compared among the different stent designs. Results show that the printed area does not predict prolapse, and that the proposed index (PI) does correlate with tissue prolapse.

3D collagen cultures under well-defined dynamic strain: A novel strain device with a porous elastomeric support

The field of mechanobiology has grown tremendously in the past few decades, and it is now well accepted that dynamic stresses and strains can impact cell and tissue organization, cell–cell and cell–matrix communication, matrix remodeling, cell proliferation and apoptosis, cell migration, and many other cell behaviors in both physiological and pathophysiological situations. Natural reconstituted matrices like collagen and fibrin are often used for three‐dimensional (3D) mechanobiology studies because they naturally form fibrous architectures and are rich in cell adhesion sites; however, they are physically weak and typically contain >99% water, making it difficult to apply dynamic stresses to them in a truly 3D context. Here we present a composite matrix and strain device that can support natural matrices within a macroporous elastic structure of polyurethane. We characterize this system both in terms of its mechanical behavior and its ability to support the growth and in vivo‐like behaviors of primary human lung fibroblasts cultured in collagen. The porous polyurethane was created with highly interconnected pores in the hundreds of µm size scale, so that while it did not affect cell behavior in the collagen gel within the pores, it could control the overall elastic behavior of the entire tissue culture system. In this way, a well‐defined dynamic strain could be imposed on the 3D collagen and cells within the collagen for several days (with elastic recoil driven by the polyurethane) without the typical matrix contraction by fibroblasts when cultured in 3D collagen gels. We show lung fibroblast‐to‐myofibroblast differentiation under 30%, 0.1 Hz dynamic strain to validate the model and demonstrate its usefulness for a wide range of tissue engineering applications. Biotechnol. Bioeng. 2009;103: 217–225.

Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix.

Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6 μm, a specific surface area of 40 m(2)/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16 nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200 μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15 days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales.

Computational fluid dynamics in a model of the total cavopulmonary connection reconstructed using magnetic resonance images.

The recent developments in imaging techniques have created new opportunities to give an accurate description of the three-dimensional morphology of vessels. Such three-dimensional reconstruction of anatomical structures from medical images has achieved importance in several applications, such as the reconstruction of human bones, spine portions, and vascular districts.

Design and characterization of microcapsules-integrated collagen matrixes as multifunctional three-dimensional scaffolds for soft tissue engineering.

Three-dimensional (3D) porous scaffolds based on collagen are promising candidates for soft tissue engineering applications. The addition of stimuli-responsive carriers (nano- and microparticles) in the current approaches to tissue reconstruction and repair brings about novel challenges in the design and conception of carrier-integrated polymer scaffolds. In this study, a facile method was developed to functionalize 3D collagen porous scaffolds with biodegradable multilayer microcapsules. The effects of the capsule charge as well as the influence of the functionalization methods on the binding efficiency to the scaffolds were studied. It was found that the binding of cationic microcapsules was higher than that of anionic ones, and application of vacuum during scaffolds functionalization significantly hindered the attachment of the microcapsules to the collagen matrix. The physical properties of microcapsules-integrated scaffolds were compared to pristine scaffolds. The modified scaffolds showed swelling ratios, weight losses and mechanical properties similar to those of unmodified scaffolds. Finally, in vitro diffusional tests proved that the collagen scaffolds could stably retain the microcapsules over long incubation time in Tris-HCl buffer at 37°C without undergoing morphological changes, thus confirming their suitability for tissue engineering applications. The obtained results indicate that by tuning the charge of the microcapsules and by varying the fabrication conditions, collagen scaffolds patterned with high or low number of microcapsules can be obtained, and that the microcapsules-integrated scaffolds fully retain their original physical properties.

Bio-Hybrid Scaffolds for Bone Tissue Engineering: Nano-Hydroxyapatite/Chitosan Composites

Natural bone ECM is a hierarchical nanocomposite made of an inorganic phase deposited within an organic matrix. In order to mimic the bone highly organized hybrid structure and functionality, strategies that allow assembling ceramic and polymer phase can be applied. To this aim, we investigated an insitu growth method able to nucleate a nanoHydroxyapatite (nHAp) phase into and around the interconnected porous structure of chitosan sponges. By increasing the calcium and phosphate concentration in the meta-stable solution used for the nHAp nucleation, the inorganic phase raised proportionally, in the range 10%-30% wt. In order to be compared with nHAp loaded scaffolds, pure chitosan samples have been produced by cross-linking biopolymer with arginine. Moreover, nHAp loaded samples, containing the 20 % wt of inorganic phase have been prepared by simply mixing low crystalline nHAp powders with the chitosan gel. The in situ nucleation method highlighted evident advantages in terms of nanophase distribution and mechanical performances with respect to a merely mixing procedure.

3D printing of hydroxyapatite polymer-based composites for bone tissue engineering

Abstract Skeletal defects reconstruction, using custom-made substitutes, represents a valid solution to replacing lost and damaged anatomical bone structures, renew their original function, and at the same time, restore the original aesthetic aspect. Rapid prototyping (RP) techniques allow the construction of complex physical models based on 3D clinical images. However, RP machines usually work with synthetic polymers; therefore, producing custom-made scaffolds using a biocompatible material directly by RP is an exciting challenge. The aim of the present work is to investigate the potentiality of 3D printing as a manufacturing method to produce an osteogenic hydroxyapatite-polylactic acid bone graft substitute.