Biomedical subjects

Paolo A Netti

Publications and source records attributed to Paolo A Netti.

5 recordsLinked to original sources

PubMed2007

Induction of directional sprouting angiogenesis by matrix gradients.

The fate of any tissue engineering implant relies upon an adequate oxygen and nutrients supply throughout the cellular construct and, hence, by the ability of the scaffold to induce and guide vascular ingrowth. However, implant vascularization is usually an uncontrolled process that takes several weeks. In this work, we assessed the feasibility of controlling vascular sprout rate and direction within three-dimensional collagen-hyaluronic acid semi-interpenetrated networks by modulating the spatial distribution of the matricellular cues. Results indicated that increasing amount of hyaluronic acid (HA) within the matrix led to a progressive inhibition of sprouting. In HA-rich matrices, the sprout number and the propagation rate showed a 2.7- and 4-fold reduction, respectively, compared to collagen matrices. Furthermore, by creating HA gradients within the collagen network, we were able to direct and enhance the sprouting rate. This study provides an experimental platform for controlling vascularization of engineered tissues.

Animals↗

PubMed2005

The effect of matrix composition of 3D constructs on embryonic stem cell differentiation.

The use of embryonic stem (ES) cells as unlimited cell source in tissue engineering has ignited the hope of regenerating any kind of tissue in vitro. However, the role of the material in control and guidance of their development and commitment into complex and viable three-dimensional (3D) tissues is still poorly understood. In this work, we investigate the role of material composition and structure on promoting ES cells growth and differentiation, by culturing mouse ES cell-derived embryoid bodies (EBs) in various semi-interpenetrating polymer networks (SIPNs), made of collagen, fibronectin (FN) and laminin (LM). We show that both composition and strength of the supportive matrix play an important role in EBs development. High collagen concentrations inhibit EBs cavitation and hence the following EBs differentiation, by inhibiting apoptosis. The presence of FN in 3D collagen constructs strongly stimulates endothelial cell differentiation and vascularization. Conversely, LM increases the ability of ES cells to differentiate into beating cardiomyocytes. Our data suggest that matrix composition has an important role in EBs development and that it is possible to influence stem cell differentiation toward preferential pattern, by modulating the physical and biochemical properties of the scaffold.

Animals↗

PubMed2004

Preparation and physico-chemical characterisation of microporous polysaccharidic hydrogels.

A new technique to obtain microporous hydrogels was realised. It permits us to obtain a microporous structure directly on the already cross-linked hydrogel. It consists in stratifying the already cross-linked hydrogel on to a filter with known porosity and forcing the CO2 bubbles, derived from the addition of HCl to a porogen salt (NaHCO3), to cross through the filter first and then the matrix. By changing the porosity of the filter, it was possible to modulate the porous morphology of the hydrogels. The polysaccharides selected were hyaluronane, alginate, and carboxymethylcellulose. The influence of the porous morphology on the physico-chemical properties of the gel has been evaluated by FT-IR, FRAP, calorimetric, water uptake, and rheological analysis.

Biocompatible Materials↗

PubMed2003

A model for temporal heterogeneities of tumor blood flow.

Tumor blood flow (TBF) plays a fundamental role in tumor growth and treatment, and is characterized by spatial and temporal heterogeneities. Here we show that the interstitial fluid pressure (IFP), which is higher in tumoral tissue than in normal tissue, coupled with the tumor microvascular pressure (MVP) and the higher permeability of tumoral vessels, can explain the sustained oscillatory behavior of TBF, observed in vivo.

Animals↗

PubMed2003

Solid stress generated by spheroid growth estimated using a linear poroelasticity model.

The unchecked growth of a solid tumor produces solid stress, causing deformation of the surrounding tissue. This stress can result in clinical complications, especially in confined environments such as the brain, and may also be responsible for pathophysiological anomalies such as the collapse of blood and lymphatic vessels. High stress levels may also inhibit further cell division within tumors. Unfortunately, little is known about the dynamics of stress accumulation in tumors or its effects on cell biology. We present a mathematical model for tumor growth in a confined, elastic environment such as living tissue. The model, developed from theories of thermal expansion using the current configuration of the material element, allows the stresses within the growing tumor and the surrounding medium to be calculated. The experimental observation that confining environments limit the growth of tumor spheroids to less than the limit imposed by nutrient diffusion is incorporated into the model using a stress dependent rate for tumor growth. The model is validated against experiments for MU89 tumor spheroid growth in Type VII agarose gel. Using the mathematical model and the experimental evidence we show that the tumor cell size is reduced by solid stress inside the tumor spheroid. This leads to the interesting possibility that cell size could be a direct indicator of solid stress level inside the tumors in clinical setting.

Animals↗