In vitro degradation and bioactivity of composite poly-l-lactic (PLLA)/bioactive glass (BG) scaffolds: comparison of 45S5 and 1393BG compositions

The objective of this study was to compare the effect of two bioglass (BG) compositions 45S5 and 1393 in poly-l-lactic composite scaffolds in terms of morphology, mechanical properties, biodegradation, water uptake and bioactivity. The scaffolds were produced via thermally induced phase separation starting from a ternary polymer solution (polymer/solvent/non-solvent). Furthermore, different BG to polymer ratios have been selected (1, 2.5, 5% wt/wt) to evaluate the effect of the amount of filler on the composite structure. Results show that the addition of 1393BG does not affect the scaffold morphology, whereas the 45S5BG at the highest amount tends to appreciably modify the scaffold architecture interacting with the phase separation process. Bioactivity tests confirmed the formation of a hydroxycarbonateapatite-layer in both types of BGs (detected via scanning electron microscopy, X-ray diffractometry and Fourier Transform Infrared Spectroscopy). Overall, the results showed that 1393BG composition affects the experimental preparation protocol to a minimal extent thus allowing a better control of the scaffold\ue2\u80\u99s morphology compared to 45S5BG

3D cultures of rat astrocytes and brain capillary endothelial cells on Poly-L-lactic acid scaffolds

Tissue engineering is an emerging multidisciplinary field that aims at reproducing in vitro and/or in vivo tissues with morphological and functional features similar to the biological tissue of the human body. In this communication we report setting of three-dimensional structures able to mimic the extracellular matrix of the nervous system: we prepared Poly-L-Lactic Acid (PLLA) porous scaffolds via thermally induced phase separation (TIPS), and investigated the parameters that influence porosity, average pore size and degree of interconnection, i.e. polymer concentration, temperature and time of process. Astrocytes and brain capillary endothelial cells (BCECs) were cultured on these three-dimensional structures and tested for their ability to grow and survive on PLLA scaffolds. We analyzed in parallel the cell growth in 2D and 3D culture systems and observed the differences in cell morphology by fluorescence analysis: three-dimensional scaffolds have the ability to guide cell growth, provide support, encourage cell adhesion and proliferation. Astrocytes and BCECs adapted well to these porous matrices, not only remaining on the surface, but also penetrating inside the scaffolds. This 3D cell culture system could be further enriched to host two or three different brain cell types, in order to set an in vitro model of blood brain barrier, that may be useful for drug delivery studies, and for the formulation of new therapeutic strategies, to be used for the treatment of neurological diseases

Engineering approaches in siRNA delivery

siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors\ue2\u80\u99 production processes and siRNAs vectors\ue2\u80\u99 release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors\ue2\u80\u99 fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications