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Parkinson's disease (PD) is a progressive neurodegenerative disease with no satisfactory therapy options. Similar to other neurodegenerative conditions, such as Alzheimer's and Huntington's diseases, oxidative stress plays a key factor in the neurodegeneration process. To counteract the uncontrolled increase of reactive oxygen species (ROS) and oxidative stress-dependent cell death, several preclinical and clinical tests exploit natural-derived organic antioxidants, such as polyphenols. Despite some promising results, free antioxidants show scarce brain accumulation and may exhaust their scavenging activity before reaching the brain. In this work, we developed an antioxidant therapeutic nanoplatform consisting of nano-sized functionalized liposomes loaded with selected polyphenol-rich vegetal extracts with high blood-brain barrier crossing capabilities. The antioxidant extracts were obtained from the grape seeds and skins as a byproduct of wine production (i.e., pomace), following a sustainable circular approach with reduced environmental impact. The antioxidant nanoplatform was successfully tested in a relevant in vitro model of PD, where it completely rescued the ROS levels, prevented the aggregation of α-synuclein fibrils, and restored cell viability, paving the way for preclinical translation of the approach.

Parkinson's disease (PD) is a progressive neurodegenerative disease with no satisfactory therapy options. Similar to other neurodegenerative conditions, such as Alzheimer's and Huntington's diseases, oxidative stress plays a key factor in the neurodegeneration process. To counteract the uncontrolled increase of reactive oxygen species (ROS) and oxidative stress-dependent cell death, several preclinical and clinical tests exploit natural-derived organic antioxidants, such as polyphenols. Despite some promising results, free antioxidants show scarce brain accumulation and may exhaust their scavenging activity before reaching the brain. In this work, we developed an antioxidant therapeutic nanoplatform consisting of nano-sized functionalized liposomes loaded with selected polyphenol-rich vegetal extracts with high blood-brain barrier crossing capabilities. The antioxidant extracts were obtained from the grape seeds and skins as a byproduct of wine production (

FULL CONFERENCE PAPER "Two-step MEMS microfabrication via 3D direct laser lithography", Proceeding of Advanced Fabrication Technologies for Micro/Nano Optics and Photonics XIV; 116960J (2021) (Event: SPIE OPTO, 2021, Online Only) DOI: 10.1117/12.2579213 ABSTRACT: Micro/nano electro-mechanical systems (MEMS/NEMS) are constantly attracting an increasing attention for their relevant technological applications in fields ranging from biology, medicine, ecology, energy to industry. Most of the performances of micro-nanostructured devices rely on both the design and the intrinsic properties of the constituent materials that are processed at such dimensional scale. For this reason, spatial precision, resolution and reproducibility are crucial factors in the micro-fabrication procedure. 3D direct laser lithography (DLL), based on multiphoton absorption, allows to realize outstanding three-dimensional structures with nanoscale features. This technique has recently emerged as a powerful tool for fabricating 3D micro-patterned surfaces for optics, photonics, as well as for bioinspired cell culture scaffold. We propose a method for a two-step fabrication of micro/nanostructured multicomponent systems to be employed as transductors, by means of the integration of 3D DLL and shadowing effects in metal deposition. A z-axis accelerometer is the proof-of-concept for the validation of the proposed transductor. The former is composed of a cantilever patterned with conductive paths which act as a strain gauge. Mechanical stimulation deforms the cantilever and, accordingly, varies its conductive properties. The fabrication of the conductive components is performed using the vacuum evaporation of gold, a traditional microfabrication technique, and exploiting the shadowing effect due to peculiar microstructures on the cantilever, The authors acknowledge funding from the European Horizon 2020 Research and Innovation Programme under Grant Agreement No 899349 (5D NanoPrinting).

Tetrapyrroles are the basis of essential physiological functions in most living organisms. These compounds represent the basic scaffold of porphyrins, chlorophylls, and bacteriochlorophylls, among others. Chlorophyll derivatives, obtained by the natural or artificial degradation of chlorophylls, present unique properties, holding great potential in the scientific and medical fields. Indeed, they can act as cancer-preventing agents, antimutagens, apoptosis inducers, efficient antioxidants, as well as antimicrobial and immunomodulatory molecules. Moreover, thanks to their peculiar optical properties, they can be exploited as photosensitizers for photodynamic therapy and as vision enhancers. Most of these molecules, however, are highly hydrophobic and poorly soluble in biological fluids, and may display undesired toxicity due to accumulation in healthy tissues. The advent of nanomedicine has prompted the development of nanoparticles acting as carriers for chlorophyll derivatives, facilitating their targeted administration with demonstrated applicability in diagnosis and therapy. In this review, the chemical and physical properties of chlorophyll derivatives that justify their usage in the biomedical field, with particular regard to light-activated dynamics are described. Their role as antioxidants and photoactive agents are discussed, introducing the most recent nanomedical applications and focusing on inorganic and organic nanocarriers exploited in vitro and in vivo.

Interfaces between conjugated polymers and aqueous electrolytes are gaining increasing interest for a number of different applications, including electrochemical cells, biosensors and functional organic devices for recording and stimulating the bioelectrical activity. In this field, devices sensitive to visible light are particularly interesting, both for inducing solar-driven photo-electrochemical reactions and for spatially selective, not-invasive optical control of living systems. We demonstrate that photoexcitation of the conjugated polymer leads to both capacitive and faradaic electrical signals at the interface with water. We introduce here a mesoporous, light sensitive polymer/electrolyte interface, we characterize its behavior and we reproduce the experimental data with an equivalent circuit model. Interestingly, we show that the use of polymer-based mesoporous devices offers a practical and simple handle for the modulation of the interface behavior. Device engineering allows to control the sign of charges at the polymer surface and to balance faradaic and capacitive currents established at the interface with water. This work opens up interesting opportunities towards applications in both photo-electrochemistry and biology.

Light and semiconducting polymers induce angiogenesis in vitro., The control of stem and progenitor cell fate is emerging as a compelling urgency for regenerative medicine. Here, we propose a innovative strategy to gain optical control of endothelial colony-forming cell fate, which represents the only known truly endothelial precursor showing robust in vitro proliferation and overwhelming vessel formation in vivo. We combine conjugated polymers, used as photo-actuators, with the advantages offered by optical stimulation over current electromechanical and chemical stimulation approaches. Light modulation provides unprecedented spatial and temporal resolution, permitting at the same time lower invasiveness and higher selectivity. We demonstrate that polymer-mediated optical excitation induces a robust enhancement of proliferation and lumen formation in vitro. We identify the underlying biophysical pathway as due to light-induced activation of TRPV1 channel. Altogether, our results represent an effective way to induce angiogenesis in vitro, which represents the proof of principle to improve the outcome of autologous cell-based therapy in vivo.

Hybrid interfaces between living cells and nano/microstructured scaffolds have huge application potential in biotechnology, spanning from regenerative medicine and stem cell therapies to localized drug delivery and from biosensing and tissue engineering to neural computing. However, 3D architectures based on semiconducting polymers, endowed with responsivity to visible light, have never been considered. Here, we apply for the first time a push-coating technique to realize high aspect ratio polymeric pillars, based on polythiophene, showing optimal biocompatibility and allowing for the realization of soft, 3D cell cultures of both primary neurons and cell line models. HEK-293 cells cultured on top of polymer pillars display a remarkable change in the cell morphology and a sizable enhancement of the membrane capacitance due to the cell membrane thinning in correspondence to the pillars' top surface, without negatively affecting cell proliferation. Electrophysiology properties and synapse number of primary neurons are also very well preserved. In perspective, high aspect ratio semiconducting polymer pillars may find interesting applications as soft, photoactive elements for cell activity sensing and modulation. Hybrid interfaces between living cells and nano/microstructured scaffolds have huge application potential in biotechnology, spanning from regenerative medicine and stem cell therapies to localized drug delivery and from biosensing and tissue engineering to neural computing. However, 3D architectures based on semiconducting polymers, endowed with responsivity to visible light, have never been considered. Here, we apply for the first time a push-coating technique to realize high aspect ratio polymeric pillars, based on polythiophene, showing optimal biocompatibility and allowing for the realization of soft, 3D cell cultures of both primary neurons and cell line models. HEK-293 cells cultured on top of polymer pillars display a remarkable change in the cell morphology and a sizable enhancement of the membrane capacitance due to the cell membrane thinning in correspondence to the pillars' top surface, without negatively affecting cell proliferation. Electrophysiology properties and synapse number of primary neurons are also very well preserved. In perspective, high aspect ratio semiconducting polymer pillars may find interesting applications as soft, photoactive elements for cell activity sensing and modulation.

The control of stem and progenitor cell fate is emerging as a compelling urgency for regenerative medicine. Here, we propose a innovative strategy to gain optical control of endothelial colony-forming cell fate, which represents the only known truly endothelial precursor showing robust in vitro proliferation and overwhelming vessel formation in vivo. We combine conjugated polymers, used as photo-actuators, with the advantages offered by optical stimulation over current electromechanical and chemical stimulation approaches. Light modulation provides unprecedented spatial and temporal resolution, permitting at the same time lower invasiveness and higher selectivity. We demonstrate that polymer-mediated optical excitation induces a robust enhancement of proliferation and lumen formation in vitro. We identify the underlying biophysical pathway as due to light-induced activation of TRPV1 channel. Altogether, our results represent an effective way to induce angiogenesis in vitro, which represents the proof of principle to improve the outcome of autologous cell-based therapy in vivo.

In this work, we report the first demonstration of a solution processable, optically switchable 1D photonic crystal by implementing phototunable doped metal oxide nanocrystals. The resulting device structure shows bi-photonic response with the photonic bandgap covering the visible spectral range and the plasmon resonance of the doped metal oxide the near infrared. By means of a facile photodoping process, we tuned the plasmonic response and switched effectively the optical properties of the photonic crystal, translating the effect from the near infrared to the visible. The ultrafast bandgap pumping induces a signal change in the region of the photonic stopband, with recovery times of several picoseconds, providing a step toward the ultrafast optical switching. Optical modeling uncovers the importance to understand largely the variations of the dielectric function of the photodoped material, and variations in the high frequency region of the Drude response are responsible for the strong switching in the visible after photodoping. Our device configuration offers unprecedented tunablility due to flexibility in device design, cover wavelength ranges from the visible to the near infrared. Our findings indicate a new protocol to modify the optical response of photonic devices by optical triggers only., Comment: 12 pages, 3 figures

Fast and controllable surface acoustic wave (SAW) driven digital microfluidic temperature changes are demonstrated. Within typical operating conditions, the direct acoustic heating effect is shown to lead to a maximum temperature increase of about 10 °C in microliter water droplets. The importance of decoupling droplets from other on-chip heating sources is demonstrated. Acoustic-heating-driven temperature changes reach a highly stable steady-state value in ?3 s, which is an order of magnitude faster than previously published. This rise time can even be reduced to ?150 ms by suitably tailoring the applied SAW-power excitation profile. Moreover, this fast heating mechanism can lead to significantly higher temperature changes (over 40 °C) with higher viscosity fluids and can be of much interest for on-chip control of biological and/or chemical reactions. Fast and controllable surface acoustic wave (SAW) driven digital microfluidic temperature changes are demonstrated. Small temperature changes in typical SAW microfluidic conditions and the possibility for rapid and controllable high temperature changes, for use with lab-on-a-chip devices, are shown.

A tuning of the light transmission properties of 1D photonic structures employing an external stimulus is very attracting and opens the way to the fabrication of optical switches for colour manipulation in sensing, lighting, and display technology. We present the electric field-induced tuning of the light transmission in a photonic crystal device, made by alternating layers of silver nanoparticles and titanium dioxide nanoparticles. We show a shift of around 10 nm for an applied voltage of 10 V. We ascribe the shift to an accumulation of charges at the silver/TiO2 interface due to electric field, resulting in an increase of the number of charges contributing to the plasma frequency in silver, giving rise to a blue shift of the silver plasmon band, with concomitant blue shift of the photonic band gap. The employment of a relatively low applied voltage gives the possibility to build a compact and low-cost device. We also propose the fabrication of 1D photonic crystal and microcavities employing a magneto-optical material as TGG (Tb3Ga5O12). With these structures we can observe a shift of 22 nm with a magnetic field of 5 T, at low temperature (8 K). The option to tune the colour of a photonic crystal with magnetic field is interesting because of the possibility to realize contactless optical switches. We also discuss the possibility to achieve the tuning of the photonic band gap with UV light in photonic crystals made with indium tin oxide (ITO)., 7 pages, 3 figures

We present the electric field-induced tuning of the light transmission in a photonic crystal device. The device, with alternating layers of Silver and Titanium dioxide nanoparticles, shows a shift of around 10 nm for an applied voltage of 10 V. An accumulation of charges at the Silver/TiO2 interface due to electric field leads to an increase of the number of charges contributing to the plasma frequency in Silver. This results in a blue shift of the Silver plasmon band, with concomitant blue shift of the photonic band gap as a result of the decrease in the Silver dielectric function.

Nondeterministic phenomena are at the base of plenty of biological processes that comprise physiological signaling, cellular communications, and biological architectures. Among them, natural surface topographies are often characterized by "chaotic" features that are not trivial to be recreated in vitro. Recently, some methods have been proposed to resemble the hierarchical organization of the extracellular microenvironment, through the chemical preparation of randomly rough and self-affine fractal surfaces. Notwithstanding, this approach does not allow the fractal dimension to be modulated at a desired value, being moreover the self-affinity maintained just for one decade of spatial frequencies. Here, we propose the replication of in silico generated Brownian surfaces through a two-photon polymerization technique. As a result of the direct laser writing of the desired patterns, we were able to obtain highly reproducible self-affine (in a range of two spatial frequency decades) structures characterized by the desired predetermined Hurst exponents. Rat mesenchymal stem cells were moreover cultured on the obtained substrates, highlighting interesting phenomena concerning cell adhesion, cytoskeleton conformation, and actin polymerization, strictly depending on the fractal dimension of the surfaces.

We report on the fabrication and characterization of a freestanding ultrathin, mucoadhesive gold nanoshell/polysaccharide multilayer nanocomposite (thermonanofilm, TNF), that can be used for controlled photothermal ablation of tissues through irradiation with near-infrared radiation (NIR) laser. The aim of this work is to provide a new strategy to precisely control particle concentration during photothermalization of cancerous lesions, since unpredictable and aspecific biodistributions still remains the central issue of inorganic nanoparticle-assisted photothermal ablation. Gold nanoshell encapsulation in polysaccharide matrix is achieved by drop casting deposition method combined with spin-assisted layer-by-layer (LbL) assembly. Submicrometric thickness of films ensures tissue adhesion. Basic laser-induced heating functionality has been demonstrated by in vitro TNF-mediated thermal ablation of human neuroblastoma cancer cells, evidenced by irreversible damage to cell membranes and nuclei. Ex vivo localized vaporization and carbonization of animal muscular tissue is also demonstrated by applying TNF onto tissue surface. Thermal distribution in the tissue reaches a steady state in a few seconds, with significant increases in temperature (ΔT50) occurring across an 1 mm span, ensuring control of local photothermalization and providing more safety and predictability with respect to traditional laser surgery. A steady-state model of tissue thermalization mediated by TNFs is also introduced, predicting the temperature distribution being known the absorbance of TNFs, the laser power, and the tissue thermal conductivity, thus providing useful guidelines in the development of TNFs. Thermonanofilms can find applications for local photothermal treatment of cancerous lesions and wherever high precision and control of heat treatment is required.

A novel drug delivery vector, a free-standing polymeric ultrathin film (nanofilm) composed of PMMA and a polysaccharides multilayer, is presented. Chitosan and sodium alginate are alternatively deposited by spin-assisted LbL assembly onto a plasma-treated PMMA thin film. Hydrophobic anti-inflammatory drugs, an adenosine deaminase inhibitor (APP) and its fluorescent dansyl derivate (APP-Dns), are encapsulated inside the LbL multilayer using a simple casting deposition procedure. The resulting drug loaded nanofilm can be suspended in water upon dissolution of a PVA sacrificial layer. Morphological characterization of the nanofilm shows that PMMA/LbL nanofilms possess nanometric thickness (

The degeneration of photoreceptors in the retina is one of the major causes of adult blindness in humans. Unfortunately, no effective clinical treatments exist for the majority of retinal degenerative disorders. Here we report on the fabrication and functional validation of a fully organic prosthesis for long-term in vivo subretinal implantation in the eye of Royal College of Surgeons rats, a widely recognized model of retinitis pigmentosa. Electrophysiological and behavioural analyses reveal a prosthesis-dependent recovery of light sensitivity and visual acuity that persists up to 6–10 months after surgery. The rescue of the visual function is accompanied by an increase in the basal metabolic activity of the primary visual cortex, as demonstrated by positron emission tomography imaging. Our results highlight the possibility of developing a new generation of fully organic, highly biocompatible and functionally autonomous photovoltaic prostheses for subretinal implants to treat degenerative blindness. A retinal prosthesis fabricated from an organic photovoltaic polymer can restore degenerative blindness in vivo, and over long implantation periods.

Freely suspended nanocomposite thin films based on soft polymers and functional nanostructures have been widely investigated for their potential application as active elements in microdevices. However, most studies are focused on the preparation of nanofilms composed of polyelectrolytes and charged colloidal particles. Here, a new technique for the preparation of poly(l-lactic acid) free-standing nanofilms embeddidng superparamagnetic iron oxide nanoparticles is presented. The fabrication process, based on a spin-coating deposition approach, is described, and the influence of each production parameter on the morphology and magnetic properties of the final structure is investigated. Superparamagnetic free-standing nanofilms were obtained, as evidenced by a magnetization hysteresis measurement performed with a superconducting quantum interference device (SQUID). Nanofilm surface morphology and thickness were evaluated by atomic force microscopy (AFM), and the nanoparticle dispersion inside the composites was investigated by transmission electron microscopy (TEM). These nanofilms, composed of a biodegradable polyester and remotely controllable by external magnetic fields, are promising candidates for many potential applications in the biomedical field.

INTRODUCTION Various hydrogel materials have been developed for use as delivery vehicles of bioactive molecules and cells in tissue engineering. In this respect, injectable hydrogel materials, which can gel under physiological conditions, hold great potential. Injectable materials eliminate the need of complicated surgery for implantation, which allows minimally invasive procedures for tissue repair. Cells and bioactive factors can be incorporated easily in the system and injected to the defect site. Moreover, injectable hydrogels can take the shape of the defect to be regenerated, thus eliminating the need for precise prefabrication of the scaffold. Both hard and soft tissues may be targeted depending on the hardening mechanism. In general, in situ crosslinking leads to stiff materials, whereas self-assembly gives weaker systems that are, however, less toxic because of the lack of solvents and initiators.

We investigated the self-aggregation of 12 short ionic oligopeptides constituted by 4-7 amino acid residues to establish useful structure-property relationships that might be exploited in the biomedical field by using the concept of molecular Lego. We show that the critical aggregation concentration (CAC) of tetrapeptides decreases with increasing hydrophobicity of neutral residues. Additionally, the dependence of the CAC of isomeric oligopeptides on the distribution of amino acid residues confirms the high tendency to self-organization of molecules with alternating ionic and neutral residues. Indeed, atomic force microscopy (AFM) images recorded on oligopeptide solutions above the CAC show the presence of either fibrillar or spherical aggregates depending on oligopeptide structure and concentration, steric hindrance, solution pH, and time. The potential of the investigated oligopeptides in tissue engineering applications is supported by their in vitro cytocompatibility.

The self-aggregation of two short ionic tetrapeptides (RWDW and RVDV, where R = arginine, V = valine, W = tryptophan, D = aspartic acid) was studied by different experimental techniques such as, atomic force microscopy (AFM), light scattering (LS), isothermal titration calorimetry (ITC) and viscosimetry. AFM was used to investigate the morphology of the aggregates; the AFM images showed the presence of fibrillar aggregates whose number and length increased with increasing oligopeptides concentration. On the other hand, the collected experimental calorimetric and physical chemical results consistently indicated a critical aggregation concentration (cac) around 0.5 and 2.0 mM for RWDW and RVDV respectively.

An electric field is employed for the active tuning of the structural colour in photonic crystals, which acts as an effective external stimulus with an impact on light transmission manipulation. In this work, we demonstrate structural colour in a photonic crystal device comprised of alternating layers of silver nanoparticles and titanium dioxide nanoparticles, exhibiting spectral shifts of around 10 nm for an applied voltage of only 10 V. The accumulation of charge at the metal/dielectric interface with an applied electric field leads to an effective increase of the charges contributing to the plasma frequency in silver. This initiates a blue shift of the silver plasmon band with a simultaneous blue shift of the photonic band gap as a result of the change in the silver dielectric function (i.e. decrease of the effective refractive index). These results are the first demonstration of active colour tuning in silver/titanium dioxide nanoparticle-based photonic crystals and open the route to metal/dielectric-based photonic crystals as electro-optic switches.

In order to integrate electroconductive properties in a Liquid Single Crystal Elastomer (LSCE) and to test direct actuation of the LSCE by Joule heating, we present a new bi-layered all-organic composite actuator based on the coupling of a nematic LSCE with a conductive polymer. The bending actuator is fabricated by depositing a thin conductive polymer layer of poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) over the surface of a polysiloxane-based monodomain nematic LSCE film. Mechanical properties of PEDOT:PSS, better matched with LSCE ones compared with metals or inorganic nanoparticles used in other approaches, allowed us to develop an all-organic reliable millimetre-scale actuating composite. The thermally induced elongation/compression of the LSCE over 30% is exploited for the fabrication of bending actuators with curvature up to κ = 0.64 mm−1. The LSCE and the composite material are characterized as regards their thermo-mechanical and electrical properties. A model is introduced to describe bending of the composite as a function of the thermo-mechanical properties of the LSCE, and the model is assessed by comparing the model results with the experimental findings. Bending actuation via direct Joule heating of the composite is also assessed by supplying the necessary current (50 mA at 1.3 V) through wires connected to the composite. These results open new possibilities for the application of LCEs in the micro and soft robotics fields, as well as in the biomedical field.

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.

Investigation of the interactions between cells and material surfaces is important not only for the understanding of cell biology but also for the development of smart biomaterials. In this study, we investigated the substrate-related effects on the interaction between cell and polymeric ultrathin film (nanosheet) by modulating the mechanical properties of the nanosheet with a metal substrate or mesh. A freestanding polymeric nanosheet with tens-of-nanometers thickness composed of poly(L-lactic acid) (PLLA nanosheet) was fabricated by combination of a spin-coating technique and a water-soluble sacrificial layer. The freestanding PLLA nanosheet was collected on a stainless steel mesh (PLLA-mesh) and subsequently used for cell adhesion studies, comparing the results to the ones on a control SiO(2) substrate coated with an ultrathin layer of PLLA (PLLA-substrate). The adhesion of rat cardiomyocytes (H9c2) was evaluated on both samples after 24 h of culture. The PLLA-mesh with the tens-of-nanometers thick nanosheets induced an anisotropic adhesion of H9c2, while H9c2 on the PLLA-substrate showed an isotropic adhesion independent from the nanosheet thickness. Interestingly, an increment in the nanosheet thickness in the PLLA-mesh samples reduced the cellular anisotropy and led to a similar morphology to the PLLA-substrate. Considering the huge discrepancy of Young's modulus between PLLA nanosheet (3.5-4.2 GPa) and metal substrate (hundreds of GPa), cell adhesion was mechanically regulated by the Young's modulus of the underlying substrate when the thickness of the PLLA nanosheet was tens of nanometers. Modulation of the stiffness of the polymeric nanosheet by utilizing a rigid underlying material will allow the constitution of a unique cell culture environment.

Replacement strategies arise as promising approaches in case of inherited retinal dystrophies leading to blindness. A fully organic retinal prosthesis made of conjugated polymers layered onto a silk fibroin substrate is engineered. First, the biophysical and surface properties are characterized; then, the long-term biocompatibility is assessed after implantation of the organic device in the subretinal space of 3-months-old rats for a period of five months. The results indicate a good stability of the subretinal implants over time, with preservation of the physical properties of the polymeric layer and a tight contact with the outer retina. Immunoinflammatory markers detect only a modest tissue reaction to the surgical insult and the foreign body that peaks shortly after surgery and progressively decreases with time to normal levels at five months after implantation. Importantly, the integrity of the polymeric layer in direct contact with the retinal tissue is preserved after five months of implantation. The recovery of the foreign-body tissue reaction is also associated with a normal b-wave in the electroretinographic response. The results demonstrate that the device implanted in nondystrophic eyes is well tolerated, highly biocompatible, and suitable as retinal prosthesis in case of photoreceptor degeneration.