Cesare Errico

Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice

Diabetic skin ulcers are difficult to heal spontaneously due to the reduced levels and activity of endogenous growth factors. Recombinant human vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are known to stimulate cell proliferation and accelerate wound healing. Direct delivery of VEGF and bFGF at the wound site in a sustained and controllable way without loss of bioactivity would enhance their biological effects. The aim of this study was to develop a poly(ether)urethane-polydimethylsiloxane/fibrin-based scaffold containing poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with VEGF and bFGF (scaffold/GF-loaded NPs) and to evaluate its wound healing properties in genetically diabetic mice (db/db). The scaffold application on full-thickness dorsal skin wounds significantly accelerated wound closure at day 15 compared to scaffolds without growth factors (control scaffold) or containing unloaded PLGA nanoparticles (scaffold/unloaded NPs). However, the closure rate was similar to that observed in mice treated with scaffolds containing free VEGF and bFGF (scaffold/GFs). Both scaffolds containing growth factors induced complete re-epithelialization, with enhanced granulation tissue formation/maturity and collagen deposition compared to the other groups, as revealed by histological analysis. The ability of the scaffold/GF-loaded NPs to promote wound healing in a diabetic mouse model suggests its potential use as a dressing in patients with diabetic foot ulcers.

Micro/nanostructured polymeric systems for biomedical and pharmaceutical applications

This review provides an outline of the polymeric micro/nanostructured advanced systems that are suited for the controlled and targeted administration of, specifically, nonconventional drugs. The contribution of new trends in drug-delivery technology is focused on two major parts, dealing with brief surveys of: the biodegradable/bioerodible polymeric systems used in the formulation of micro/nanoparticles and techniques used in the preparation of micro/nanoparticles for their biomedical application in cancer treatment specifically, in inflammation pathologies, as oxygen carriers (blood substitutes) and in tissue-engineering practice. A small discussion of the future perspectives of the described systems is also given.

Novel electrospun polyurethane/gelatin composite meshes for vascular grafts

Novel polymeric micro-nanostructure meshes as blood vessels substitute have been developed and investigated as a potential solution to the lack of functional synthetic small diameter vascular prosthesis. A commercial elastomeric polyurethane (Tecoflex® EG-80A) and a natural biopolymer (gelatin) were successfully co-electrospun from different spinnerets on a rotating mandrel to obtain composite meshes benefiting from the mechanical characteristics of the polyurethane and the natural biopolymer cytocompatibility. Morphological analysis showed a uniform integration of micrometric (Tecoflex®) and nanometric (gelatin) fibers. Exposure of the composite meshes to vapors of aqueous glutaraldehyde solution was carried out, to stabilize the gelatin fibers in an aqueous environment. Uniaxial tensile testing in wet conditions demonstrated that the analyzed Tecoflex®–Gelatin specimens possessed higher extensibility and lower elastic modulus than conventional synthetic grafts, providing a closer matching to native vessels. Biological evaluation highlighted that, as compared with meshes spun from Tecoflex® alone, the electrospun composite constructs enhanced endothelial cells adhesion and proliferation, both in terms of cell number and morphology. Results suggest that composite Tecoflex®–Gelatin meshes could be promising alternatives to conventional vascular grafts, deserving of further studies on both their mechanical behaviour and smooth muscle cell compatibility.

Poly(hydroxyalkanoates)-Based Polymeric Nanoparticles for Drug Delivery

Poly (hydroxyalkanoates) (PHAs) have recently attracted a great deal of academic and industrial interest for their biodegradability and biocompatibility making them suitable for environmental and biomedical applications. Poly(3-hydroxybutyrate-) (PHB-) and Poly(DL-lactide-co-glycolide) (PLGA-) based nanoparticles were prepared using the dialysis method as yet unreported for the preparation of nanoparticles based on PHB. Processing conditions were varied in order to evaluate their influence on morphology, drug encapsulation, and size of nanoparticles. The relevant results obtained give a theoretical understanding of the phenomenon occurring during colloidal formation. The adopted procedure allows for a relatively small diameter and homogeneity in size distribution of the PHB nanoparticles to be obtained compared to other methods like the one based on solvent evaporation which leads to particles on microscale. The biocompatibility of PHB and relative nanoparticles was investigated and both exhibited very good cytocompatibility.

Dual-Scale Polymeric Constructs as Scaffolds for Tissue Engineering

This research activity was aimed at the development of dual-scale scaffolds consisting of three-dimensional constructs of aligned poly(ε-caprolactone) (PCL) microfilaments and electrospun poly(lactic-co-glycolic acid) (PLGA) fibers. PCL constructs composed by layers of parallel microsized filaments (0/90° lay-down pattern), with a diameter of around 365 μm and interfilament distance of around 191 μm, were produced using a melt extrusion-based additive manufacturing technique. PLGA electrospun fibers with a diameter of around 1 μm were collected on top of the PCL constructs with different thicknesses, showing a certain degree of alignment. Cell culture experiments employing the MC3T3 murine preosteoblast cell line showed good cell viability and adhesion on the dual-scale scaffolds. In particular, the influence of electrospun fibers on cell morphology and behavior was evident, as well as in creating a structural bridging for cell colonization in the interfilament gap.

Retinyl palmitate–loaded poly(lactide-co-glycolide) nanoparticles for the topical treatment of skin diseases

Nanoparticles were prepared with poly(lactide-co-glycolide), Pluronic F127, and phospholipids and loaded with retinyl palmitate. Morphology and physicochemical properties of these nanoparticles were determined by atomic force microscopy, light scattering, and zeta potential. The elasticity and deformability of the nanoparticles were correlated to Tg values measured by differential scanning calorimetry. The in vitro cytotoxicity and genotoxicity of the nanosystems were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell membrane asymmetry, and Ames tests with BALB/3T3 mouse embryo fibroblasts and HaCaT human keratinocytes cell lines. The reactive oxygen species levels and cytokine production in response to the exposure of cells to these nanoparticles were investigated, as well as the penetration in human skin culture.

A Novel Method for the Preparation of Retinoic Acid-Loaded Nanoparticles

The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. Nanoparticles with an average diameter size of 70 nm and good morphology were prepared. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells, which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity of RA was not affected by the encapsulation and purification processes.