Multifunctional Coatings for Robotic Implanted Device.

The objective of this study was the preparation and physico-chemical, mechanical, biological, and functional characterization of a multifunctional coating for an innovative, fully implantable device. The multifunctional coating was designed to have three fundamental properties: adhesion to device, close mechanical resemblance to human soft tissues, and control of the inflammatory response and tissue repair process. This aim was fulfilled by preparing a multilayered coating based on three components: a hydrophilic primer to allow device adhesion, a poly(vinyl alcohol) hydrogel layer to provide good mechanical compliance with the human tissue, and a layer of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) fibers. The use of biopolymer fibers offered the potential for a long-term interface able to modulate the release of an anti-inflammatory drug (dexamethasone), thus contrasting acute and chronic inflammation response following device implantation. Two copolymers, poly(vinyl acetate-acrylic acid) and poly(vinyl alcohol-acrylic acid), were synthetized and characterized using thermal analysis (DSC, TGA), Fourier transform infrared spectroscopy (FT-IR chemical imaging), in vitro cell viability, and an adhesion test. The resulting hydrogels were biocompatible, biostable, mechanically compatible with soft tissues, and able to incorporate and release the drug. Finally, the multifunctional coating showed a good adhesion to titanium substrate, no in vitro cytotoxicity, and a prolonged and controlled drug release.

Inkjet printing of protein microarrays on freestanding polymeric nanofilms for spatio-selective cell culture environment.

In the last years, an increasing interest in bio-hybrid systems for what concerns the precise control of cell-material interactions has emerged. This trend leads towards the development of new nano-structured devices such as bioMEMS, tissue-engineering scaffolds, biosensors, etc. In the present study, we focused on the development of a spatio-selective cell culture environment based on the inkjet printing of bio-patterns on polymeric ultra-thin films (nanofilms) composed of poly(methylmethacrylate) (PMMA). Freestanding PMMA nanofilms having hundreds-of-nm thickness were prepared by spin-coating. Different shapes of cell adhesion promoters such as poly (L-lysine) (PLL) were micropatterned by inkjet printing. Moreover, to promote cell adhesion, the surface of PLL microarrays was modified with fibronectin via electorostatic interaction. The selective deposition of C2C12 skeletal muscle cells was confirmed and their viability was qualitatively assessed after 24 h. The combination of muscular cells with protein micropatterned freestanding nanofilm is beneficial for the implementation of new bio-hybrid system in muscular tissue engineering.

Biodegradable microparticles designed to efficiently reach and act on cystic fibrosis mucus barrier.

Cystic fibrosis (CF) is a progressive genetic disease caused by mutations in the gene that produces the CF transmembrane conductance regulator (CFTR) protein. The malfunction of the CFTR protein causes a thick buildup of mucus in the lungs that clogs the airways and traps bacteria, thus leading to infections, extensive lung damage and respiratory failure. Micro-delivery systems are currently being investigated as an efficient way to cross the viscous and complex architecture of the CF mucus. In this study, we produced synthetic and natural microparticles (MPs) based on poly(dl­lactide­co­glycolide) (PLGA) or gellan gum through tailored water/oil emulsion procedures. Morphological and physico-chemical characterizations were carried out on both classes of MPs showing particles having diameters within suitable ranges to reach the CF airways. In vitro biocompatibility tests were also performed on both MPs using a human lung cancer cell line (A549) demonstrating that treatment with MPs induces no cytotoxic effects. Both classes of MPs were loaded with a mucolytic agent (N­acetyl cysteine, NAC) and their release kinetics evaluated using high performance liquid chromatography (HPLC). The analysis pointed out that the amount of NAC released from MPs resulted in a dose-dependent increment, with a rapid release kinetic to satisfy the requirement for inducing an early mucus degradation. Finally, mucolytic action of NAC-loaded MPs was evaluated in an artificial sputum model through its rheological analysis obtaining the lowest viscosity profile after the addition of drug-loaded MPs. Taken together, gained results allowed us to select suitable MPs as potential drug targeting platforms having a mucolytic action for CF treatment.

Microneedles for Transdermal Biosensing: Current Picture and Future Direction.

A novel trend is rapidly emerging in the use of microneedles, which are a miniaturized replica of hypodermic needles with length-scales of hundreds of micrometers, aimed at the transdermal biosensing of analytes of clinical interest, e.g., glucose, biomarkers, and others. Transdermal biosensing via microneedles offers remarkable opportunities for moving biosensing technologies and biochips from research laboratories to real-field applications, and envisages easy-to-use point-of-care microdevices with pain-free, minimally invasive, and minimal-training features that are very attractive for both developed and emerging countries. In addition to this, microneedles for transdermal biosensing offer a unique possibility for the development of biochips provided with end-effectors for their interaction with the biological system under investigation. Direct and efficient collection of the biological sample to be analyzed will then become feasible in situ at the same length-scale of the other biochip components by minimally trained personnel and in a minimally invasive fashion. This would eliminate the need for blood extraction using hypodermic needles and reduce, in turn, related problems, such as patient infections, sample contaminations, analysis artifacts, etc. The aim here is to provide a thorough and critical analysis of state-of-the-art developments in this novel research trend, and to bridge the gap between microneedles and biosensors.

Influence of nanoparticle-embedded polymeric surfaces on cellular adhesion, proliferation, and differentiation.

The development of functional substrates to direct cellular organization is important for biomedical applications such as regenerative medicine and biorobotics. In this study, we prepared freestanding polymeric ultrathin films (nanofilms) consisting of poly(lactic acid) (PLA) and magnetic nanoparticles (MNPs), and evaluated the effects of their surface properties on the organization of cardiac-like rat myoblasts (H9c2). We changed surface properties of the PLA nanofilms (i.e., roughness and wettability) as a function of MNPs concentration. We found that the incorporation of MNPs into the nanofilms enhanced both proliferation and adhesion of H9c2 cells. Through the morphological assessment of the differentiated H9c2 cells, we also found that the presence of MNPs significantly increased the fusion index and the surface area of myotubes. In conclusion, the embedding of MNPs is a simple method to tailor the physicochemical properties of the polymeric nanofilms, yet it is an effective approach to enhance the cellular morphogenesis in the field of cardiac tissue engineering for regenerative medicine and biorobotics applications.