Leonardo E. Millon

Anisotropic polyvinyl alcohol-Bacterial cellulose nanocomposite for biomedical applications.

Compliance mismatch between the synthetic graft and the surrounding native tissue has been reported as a major factor in ultimate failure of the currently used cardiovascular graft replacements. Thus, developing biomaterials that display close mechanical properties as the tissue it is replacing is an important objective in biomedical devices design. Polyvinyl alcohol (PVA) is a biocompatible hydrogel with characteristics desired for biomedical applications. It can be crosslinked by a low temperature thermal cycling process. By using a novel thermal processing method under an applied strain and with the addition of a small amount of bacterial cellulose (BC) nanofibers, an anisotropic PVA-BC nanocomposite was created. The stress-strain tensile properties of porcine aorta were closely matched in both the circumferential and the axial directions by one type of anisotropic PVA-BC nanocomposite (10% PVA with 0.3% BC at 75% initial strain and cycle 2) within physiological range, with improved resistance to further stretch beyond physiological strains. The PVA-BC nanocomposite gives a broad range of mechanical properties, including anisotropy, by controlling material and processing parameters. PVA-BC nanocomposites with controlled degree of anisotropy that closely match the mechanical properties of the soft tissue it might replace, ranging from cardiovascular to other connective tissues, can be created.

Compression properties of polyvinyl alcohol--bacterial cellulose nanocomposite.

Despite the established use of total joint replacement for the treatment of advanced degeneration of articular cartilage, component loosening due to wear and osteolysis limits the lifespan of these joint prostheses. In the present study, nanocomposites consisting of poly(vinyl alcohol) (PVA) and bacterial cellulose (BC) nanofibers were investigated as possible improved cartilage replacement materials. Nanocomposites were synthesized by adding small amounts (<1%) of BC to PVA, and subjecting the mixture to thermal cycling. The mechanical properties of the resulting material were evaluated using unconfined compression testing. By the addition of BC nanofibers to the PVA matrix, a nanocomposite with a wide range of compressive mechanical properties control was obtained, with elastic modulus values similar to those reported for native articular cartilage. The nanocomposite also showed improved strain-rate dependence and adequate viscoelastic properties. The PVA-BC nanocomposite is therefore a promising biomaterial to be considered as a possible replacement material for localized articular cartilage injuries and other orthopedic applications such as intervertebral discs.

Design and simulation of a poly(vinyl alcohol)—bacterial cellulose nanocomposite mechanical aortic heart valve prosthesis

Abstract In this study, a polymeric aortic heart valve made of poly(vinyl alcohol) (PVA)—bacterial cellulose (BC) nanocomposite is simulated and designed using a hyperelastic non-linear anisotropic material model. A novel nanocomposite biomaterial combination of 15 wt % PVA and 0.5 wt % BC is developed in this study. The mechanical properties of the synthesized PVA—BC are similar to those of the porcine heart valve in both the principal directions. To design the geometry of the leaflets an advance surfacing technique is employed. A Galerkin-based non-linear finite element method is applied to analyse the mechanical behaviour of the leaflet in the closing and opening phases under physiological conditions. The model used in this study can be implemented in mechanical models for any soft tissues such as articular cartilage, tendon, and ligament.

Synthesis, characterization and in vitro cell compatibility study of a poly(amic acid) graft/cross-linked poly(vinyl alcohol) hydrogel.

Although physically cross-linked poly(vinyl alcohol) (PVA) hydrogels have tunable mechanical properties to match that of soft tissues, such as vascular tissue, their hydrophilic nature is not conducive to cell adhesion and spreading. For applications such as small diameter vascular grafts for coronary bypass both mechanical matching and hemocompatibility are important. Poly(amic acid) (PAA), derived from ethylene diamine tetraacetic dianhydride, is a cell-compatible polymer. It was grafted/cross-linked onto physically cross-linked PVA to provide cell compatibility. Functionalization was achieved via a one-step esterification reaction using 1,3-dicyclohexylcarbodiimide as the coupling agent and 4-dimethylaminopyridine as the catalyst. The success of the grafting reaction was verified using Fourier transform infrared spectroscopy, solid-state nuclear magnetic resonance spectroscopy and X-ray photoelectron spectroscopy. The mechanical properties of the starting PVA hydrogel were largely preserved after the grafting reaction within the physiological strain range of vascular tissue. In vitro cell culture studies using primary porcine endothelial cells confirmed cell compatibility of the PAA graft PVA hydrogel, making it an attractive candidate for small diameter vascular graft development.

Characterization of anisotropic poly(vinyl alcohol) hydrogel by small- and ultra-small-angle neutron scattering

Poly(vinyl alcohol) (PVA) hydrogels are formed from PVA solution when physical cross-links form during freeze/thaw cycling. By applying a stress during the freeze/thaw process, PVA hydrogels with anisotropic mechanical properties are produced. We have used small- and ultra-small-angle neutron scattering to study the structure at length scales of 2 nm to 10 mum. By supplementing the neutron data with data from atomic force microscopy, we have probed a large range of length scales within which structural changes responsible for bulk anisotropy occur. We model the gel as interconnected PVA blobs of size 20-50 nm arranged in fractal aggregates extending to micrometers or tens of micrometers. Bulk mechanical anisotropy appears to be due to the alignment of blobs and connections between blobs. This information is essential for tailoring mechanical properties for applications where anisotropy is desirable such as to match the properties of natural tissue in coronary grafts and to control diffusive properties in active wound dressings.

Exploring cell compatibility of a fibronectin-functionalized physically crosslinked poly(vinyl alcohol) hydrogel.

Physically crosslinked poly(vinyl alcohol) (PVA) hydrogels prepared using a low-temperature thermally cycled process have tunable mechanical properties that fall within the range of soft tissues, including cardiovascular tissue. An approach to render it hemocompatible is by endothelization, but its hydrophilic nature is not conducive to cell adhesion and spreading. We investigated the functionalization reaction of this class of PVA hydrogel with fibronectin (FN) for adhesion and spreading of primary porcine radial artery cells and vascular endothelial cells. These are cells relevant to small-diameter vascular graft development. FN functionalization was achieved using a multistep reaction, but the activation step involving carbonyl diimidazole normally required for chemically crosslinked PVA was found to be unnecessary. The reaction resulted in an increase in the elastic modulus of the PVA hydrogel but is still well within the range of cardiovascular tissue. Confocal microscopy confirmed the adhesion and spreading of both cell types on the PVA-FN surfaces, whereas cells failed to adhere to the PVA control. This is a first step toward an alternative for the realization of a synthetic replacement small-diameter vascular graft.