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Bioresorbable polymeric materials have risen great interest as implants for bone tissue regeneration, since they show substantial advantages with respect to conventional metal devices, including biodegradability, flexibility, and the possibility to be easily modified to introduce specific functionalities. In the present work, an innovative nanocomposite scaffold, properly designed to show biomimetic and osteoinductive properties for potential application in bone tissue engineering, was developed. The scaffold is characterized by a multi-layer structure, completely different with respect to the so far employed polymeric implants, consisting in a poly(D,L-lactide-co-glycolide)/polyethylene glycol electrospun nanofibrous mat sandwiched between two hydrogel gelatin layers enriched with tantalum nanoparticles (NPs). The composition of the electrospun fibers, containing 10 wt% of polyethylene glycol, was selected to ensure a proper integration of the fibers in the gel phase, essential to endow the composite with flexibility and to prevent delamination between the layers. The scaffold maintained its structural integrity after six weeks of soaking in physiological solutions, albeit the gelatin phase was partially released. The combined use of gelatin, bioresorbable electrospun fibers and tantalum NPs endows the final device with biomimetic and osteoinductive properties. Indeed, results of the in vitro tests demonstrate that the obtained scaffolds clearly represent a favorable milieu for normal human bone-marrow derived mesenchymal stem cells viability and osteoblastic differentiation; moreover, inclusion of tantalum NPs in the scaffold improves cell performance with particular regard to early and late markers of osteoblastic differentiation. (C) 2022 Elsevier Ltd. All rights reserved.

Electrospinning technology is attracting increasing interest for the fabrication of several polymeric and inorganic nanofibrous materials useful for a wide range of applications. Although the intensive research performed to understand the physics of the electrospinning process, control of polymeric jet path and of fibre deposition still remains a challenge. In this work, micropatterned electrospun materials with tunable porosity are fabricated by using novel collector devices made up of a steel sheet coated with a vitreous enamel layer. The novel approach permits to modulate electrical properties of the collector, acting on charge distribution and charge diffusion properties of the vitreous enamel coating, without introducing substantial modification of the electrospinning apparatus. The proposed solution allows the achievement of novel electrospun products for all those advanced applications requiring materials with suited fibre deposition such as, microelectronics, optical and photonic devices, as well as scaffolds for tissue engineering.

Composites of a bacterial copolyester poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), P(3HB-co-3HH), with flax fibers were investigated. A satisfactory reinforcing effect was observed in composites prepared by compression molding and using long fiber mats (long fiber composites, LFC). On the other hand, composites obtained by batch mixing fibers with molten polymer resulted in poor mechanical properties, owing to drastic fiber shortening during processing (short fiber composites, SFC). In order to improve fiber–matrix adhesion in SFC, fibers chemically modified at the surface (by acetylation or by short-chain-PEG grafting) were also used. The best results were obtained with surface acetylated fibers. In the flax fiber composites the crystallization rate of P(3HB-co-3HH) remarkably increased compared with that of the plain polyester. The fibers displayed a nucleating effect on P(3HB-co-3HH) crystallization, whose magnitude depended on fiber surface chemistry. This feature was confirmed by the appearance of transcrystallinity in isothermal crystallisation experiments run in a hot stage of a polarized optical microscope.

The modification of surface properties of electrospun fibers, while maintaining the bulk properties of the constituting material, is among important targets of the scientific community. In this work we use Surface Initiated Atom Transfer Radical Polymerization (SI-ATRP) to modify the surface of electrospun Poly(L)lactic acid (PLLA) fibers. Fibers grafted with brushes of poly(glycerol monomethacrylate), poly(GMMA) and poly(2-(diethylamino)ethyl methacrylate), poly(DEAEMA), were obtained with the aim to confer, respectively, non-fouling and antibacterial properties to PLLA fibres. Brushes polymerization conditions were optimized to obtain polyGMMA-grafted PLLA and polyDEAEMA-grafted PLLA fibres that maintained their original morphology. Mats were characterized to demonstrate the success of PLLA fibre surface modification: -potential changed consistently in the presence of the grafted chemical species; XPS analysis of PolyGMMA-grafted fibres revealed the presence of alcoholic carbons, alcoholic oxygens and -carbons of GMMA, while the peak ascribable to the tertiary amino groups of DEAEMA was detected in PolyDEAEMA-grafted fibres; modified fibres are instantaneously wetted by water while unmodified PLLA fibres are highly hydrophobic. Future work will verify the non-fouling properties of PolyGMMA-grafted PLLA and the antibacterial properties of PolyDEAEMA-grafted PLLA.

The growing shortage of essential nutrients, such as nitrogen and phosphorous, is prompting researchers to find advanced recovery processes from wastewater derived from sewage treatment plants and other wastewater sources. In this work we propose a novel compostable electrospun filtration membrane based on poly(L-lactic acid) (PLLA), for nutrient recovery through struvite crystallization from water. Composite electrospun PLLA fibers were fabricated starting from a suspension of PLLA solution and struvite crystals. Struvite within PLLA fibers worked as a nucleant agent for additional crystallization of magnesium, ammonium and phosphate hexahydrate out of water. Morphological, structural and physical properties of the obtained membranes were studied and the ammonium concentration decrease in the analyzed water samples was measured and correlated to struvite precipitation on the electrospun membranes. The obtained compostable struvite-rich membrane can be used in agriculture to provide a nutrient-rich humus for direct application to the land.

In this work we develop nanostructured electrospun separators for lithium batteries made of Poly(vinylidene fluoride) (PVDF) loaded with either fumed silica or tin oxide nanoparticles. The use of high porosity and wide surface area material allows a massive electrolyte uptake; oxide nanoparticles are added to the polymer to increase mechanical, thermal and electrical properties of the separator with the aim to fulfil capacity and safety requirements of lithium batteries. Fiber morphology was observed by SEM and the presence of the additives inside the material was revealed by energy dissipation spectroscopy (EDS). Tensile tests, thermogravimetric measurements and differential scanning calorimetry are carried out to study mechanical properties of the separators, to quantify the inorganic fraction and to evaluate thermal properties. TEM was used to evaluate the quality of nanoparticle dispersion inside the fibers. Conductivity measurements and dielectric spectroscopy on membrane are carried out to ensure low values of electron carriers conductivity. Finally, the electrospun separators are soaked in electrolyte solution to estimate their uptake. The most remarkable effect of nanoparticles addition is a significant improvement of separator mechanical properties, namely the increase of stress at break and elongation at break.

Development of antibacterial electrospun non-woven meshes is of critical importance in several areas such as healthcare products, food packaging, water and air filtration. In this work a novel biocidal polymer, which results active against Escherichia coli and Staphylococcus aureus, was synthesized starting from the biobased ricinoleic acid monomer (RA) and processed through electrospinning in combination with a biodegradable polymer poly(butylene succinate) (PBS), through a blending approach. The optimization of electrospinning process parameters allowed fabrication of defect-free nanofibers with uniform fiber diameter distribution. The chemical, physical and mechanical properties of the obtained non woven meshes were characterized and related to mesh structure and composition. The electrospun constructs were microbiologically evaluated and antibacterials tests confirmed their high biocidal efficacy. Mortality rate of E.Coli and S.Aureus was very high and it increased with the amount of PRA in the blends. Notably, the antimicrobial performances of the meshes were retained after 3 cycles of incubation with cell bacterial suspension. The obtained biobased and biodegradable antibacterial electrospun meshes can find useful application in several sectors.

Collagen electrospun scaffolds well reproduce the structure of the extracellular matrix (ECM) of natural tissues by coupling high biomimetism of the biological material with the fibrous morphology of the protein. Structural properties of collagen electrospun fibers are still a debated subject and there are conflicting reports in the literature addressing the presence of ultrastructure of collagen in electrospun fibers. In this work collagen type I was successfully electrospun from two different solvents, trifluoroethanol (TFE) and dilute acetic acid (AcOH). Characterization of collagen fibers was performed by means of SEM, ATR-IR, Circular Dichroism and WAXD. We demonstrated that collagen fibers contained a very low amount of triple helix with respect to pristine collagen (18 and 16 % in fibers electrospun from AcOH and TFE, respectively) and that triple helix denaturation occurred during polymer dissolution. Collagen scaffolds were crosslinked by using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), a commonly employed crosslinker for electrospun collagen, and 1,4-butanediol diglycidyl ether (BDDGE), that was tested for the first time in this work as crosslinking agent for collagen in the form of electrospun fibers. We demonstrated that BDDGE successfully crosslinked collagen and preserved at the same time the scaffold fibrous morphology, while scaffolds crosslinked with EDC completely lost their porous structure. Mesenchymal stem cell experiments demonstrated that collagen scaffolds crosslinked with BDDGE are biocompatible and support cell attachment.

Two-dimensional vs three-dimensional culture conditions, such as the presence of extracellular matrix components, could deeply influence the cell fate and properties. In this paper we investigated proliferation, differentiation, survival, apoptosis, growth and neurotrophic factor synthesis of rat embryonic stem cells (RESCs) cultured in 2D and 3D conditions generated using Cultrex® Basement Membrane Extract (BME) and in poly-(L-lactic acid) (PLLA) electrospun sub-micrometric fibres. It is demonstrated that, in the absence of other instructive stimuli, growth, differentiation and paracrine activity of RESCs are directly affected by the different microenvironment provided by the scaffold. In particular, RESCs grown on an electrospun PLLA scaffolds coated or not with BME have a higher proliferation rate, higher production of bioactive nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) compared to standard 2D conditions, lasting for at least 2 weeks. Due to the high mechanical flexibility of PLLA electrospun scaffolds, the PLLA/stem cell culture system offers an interesting potential for implantable neural repair devices.

Disinfection of electrospun materials is commonly carried out by ethanol (EtOH) soaking. However, in the literature no systematic investigation on the effect of EtOH disinfection on scaffold properties is available. In this study electrospun poly( l -lactic acid) (PLLA) scaffolds were differently treated in EtOH and changes of fiber morphology, fiber surface topography and scaffold thermo-mechanical properties were evaluated. It was found that EtOH induced the formation of an amount of crystal phase, in the initially amorphous fibers, which depends on EtOH grade, soaking time and temperature. Completely amorphous PLLA (a-PLLA) and semicrystalline PLLA (sc-PLLA) scaffolds were produced by applying different EtOH treatments to as-spun PLLA scaffold. Compared to a-PLLA, sc-PLLA was stiffer and composed of fibers with rougher surface. Cell culture performed by using permanent cell line H9c2 demonstrated that changes of scaffold properties determined a different cell response, in particular in the expression of proteins correlated to cell motility and cell adhesion.

This study reports the fabrication and characterization of poly(ethylene oxide) (PEO) and poly(vinylidenefluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) nanofibrous separators for lithium-ion batteries loaded with different amounts of fumed-silica and tin oxide nanoparticles. Membrane morphological characterization (SEM, TEM) showed the presence of good-quality nanofibres containing nanoparticles. Thermal degradation and membrane mechanical properties were also investigated, and a remarkable effect of nanoparticle addition on membrane mechanical properties was found. In particular, PEO membranes were strengthened by the addition of metal oxide, whereas PVDF-CTFE membranes acquired ductility.

The present work aims at investigating the influence of electrospun Nylon 6,6 nanofibrous mat to interlaminar strength. Mode I and the Mode II fracture mechanics of virgin and nanomodified laminates are investigated. Nanomodified laminates are fabricated by interleaving an electrospun nanofibrous mats in laminate mid-plane. Double Cantilever Beam (DCB) and End Notched Flexure (ENF) tests are performed on both virgin and nanomodified configuration. Results show that electrospun nanofibrous mat is able to increase by 23.2% the mechanical energy absorbing capability and by about 5% the G IC . ENF tests reveal that the nanofibrous mats contribute to improve the maximum stress before the material crisis (6.5% of increment) and a measurable increment of (8.1%) the maximum mechanical energy that can be absorbed by the material during the crack propagation is registered. The acoustic emission (AE) technique is used to monitor both DCB and ENF tests. The AE information highlight that the nanofibrous mats mitigate the interlaminar matrix failure on both the fracture modes.

In myocardial tissue engineering the use of synthetically bioengineered flexible patches implanted in the infarcted area is considered one of the promising strategy for cardiac repair. In this work the potentialities of a biomimetic electrospun scaffold made of a commercial copolymer of (L)-lactic acid with trimethylene carbonate (P(L)LA-co-TMC) are investigated in comparison to electrospun poly(L)lactic acid. The P(L)LA-co-TMC scaffold used in this work is a glassy rigid material at room temperature while it is a rubbery soft material at 37 °C. Mechanical characterization results (tensile stress-strain and creep-recovery measurements) show that at 37 °C electrospun P(L)LA-co-TMC displays an elastic modulus of around 20 MPa and the ability to completely recover up to 10% of deformation. Cell culture experiments show that P(L)LA-co-TMC scaffold promotes cardiomyocyte proliferation and efficiently preserve cell morphology, without hampering expression of sarcomeric alpha actinin marker, thus demonstrating its potentialities as synthetic biomaterial for myocardial tissue engineering.

Biomedical applications of electrospun porous non-woven mats require a particular attention towards fibre surface properties, given the high surface area to volume ratio associated with these kind of structures. Ad hoc modication of the surface properties of electrospun fibres, while maintaining the bulk properties of the constituting material, is crucial in determining their use and it is among important targets of the scientific community. In this work we use Surface Initiated Atom Transfer Radical Polymerization (SI-ATRP) to modify the surface of electrospun Poly(L)lactic cid (PLLA) fibers. In particular, electrospun fibers grafted with poly(glycerol monomethacrylate), poly(GMMA) and poly(2-(diethylamino)ethyl methacrylate), poly(DEAEMA), brushes were obtained with the aim to confer, respectively, non-fouling and antibacterial properties to PLLA fibres.

Among various failure modes in composite laminate materials, the delamination is one of the most common. Out-of-plane stresses, repeated cyclic stresses, impact, and so on, can cause layers to separate, forming a mica-like structure of separate layers, with significant loss of mechanical strength. Delamination is widely investigated, and many techniques are developed in order to improve the material strength. The aim of the present study is to investigate the infuence of electrospun nanofibers on the mechanical behaviour of composite laminate, and in particular on the delamination strength. Nanofibers, with respect to micrometric fibres commonly used in composites, are characterized by high surface to volume and aspect ratios. Moreover they also have higher strength with respect to microfbers of the same nature due to alignment of polymer chains along the fiber axis as well as to a low density of flaws and defects. The usage of nanofibers to enhance the mechanical performances of composite has been recently investigated by researchers and examples of the use of electrospun polymer nanofibers to improve the mechanical behaviour of laminates are available in the literature. The basic idea of this work is to use electrospun polymeric nanofibers as an interleaving filler placed between adjacent plies of a laminate composite material and to study the behaviour of the specimen under two specific loading conditions. Three different kinds of Nylon 6,6 are considered, and two different types of tests are performed: the Double Cantilever Beam test and the End Notch Flexure test. The specimens are manufactured by using carbon fiber/epoxy matrix laminate prepreg. The nano-modified composites are obtained by electrospinning the nanofibers directly on the ply surfaces before lay-up, thus generating a layer of fibers with a negligible thickness compared to the ply thickness. For the specified quasi-static test, one nanofiber layer is placed in the middle of the specimens. The behaviour of nanoreinforced composites is compared with the non reinforced ones. The experiments are carried out according to the ASTM standards. For the DCB tests the trend of GIC is studied depending on the thickness of nanolayer placed in the interlay. The study is repeated for the GIIC in the ENF tests. The optimum thickness of the nanofiber interlay is determined for each test. It is observed that a mat of nanofiber interleaved between the most critical plies of the composite significantly influences the delamination resistance of the same laminate. The behaviour of the laminates is different in the four tests considered, the nanofiber toughening effect being different in each one of them. By performing DMTA analysis of the resin-nanofiber system, damping effect and tensile/bending behaviours are determined in order to built up an analytical model capable to account the effect of nanofiber sheet placed in the laminates. The model is based on the lamination theory and the stiffness contributions of nanolayers are superimposed to all the other plies contributions. A new matrix formulation is presented and considerations regarding the membrane and bending behaviour are developed. In order to account the randomness of nanofibre orientation which influences the mechanical properties of composite nano-interleaved materials a probabilistic variational model is presented and discussed.

The interest towards new elastomeric materials with low elastic modulus (E), suitable for soft tissue engineering applications (E in the range 0.1-100 MPa, according to the specific native tissue), and with controllable degradation profiles has increased significantly in the last decade. In this work new biomaterials exhibiting elastomeric properties are synthesized through reactive blending. Multiblock poly(butylene-b-triethylene succinate) copolymers (P(BSTES)) are presented and their solid-state properties, hydrolytic degradation profiles and biocompatibility are investigated and correlated with copolymer molecular structure.

Electrospun (ES) materials are considered highly promising scaffolds for tissue engineering given their particular fibrous morphology that resembles the fibrous component of tissue extracellular matrix. ES scaffolds made of commercial bioresorbable polyesters can be dramatically affected by commonly employed sterilization methods (e.g. autoclaving, ethylene oxide, -rays), thus they are usually disinfected with ethanol (EtOH) before being used in contact with a biological environment. However, even if less extensively, also EtOH disinfection might affect ES scaffold morphology and, consequently, the response of cells cultured onto them. This work aims at investigating the effect of EtOH sterilization on poly(L)lactic acid (PLLA) ES scaffold and in particular on its phase morphology (amorphous to crystalline ratio). The morphological changes of PLLA non-woven mats treated at different temperatures by using EtOH solutions with different concentration, were compared. Moreover, the behaviour of H9c2 cardiac cells seeded onto PLLA scaffolds treated with EtOH was investigated.

Nowadays, efforts are dedicated to develop new biodegradable polymers for soft tissues engineering, where scaffolds displaying high elasticity are required in order to resist to long-term cyclic strains. These mechanical performances can be achieved by few synthetic biodegradabile polymers (e.g. Degrapol®, poly(glycerol sebacate) and poly(lactide-co-trimethylene carbonate)) whereas the most extensively used polyester (e.g. polycaprolactone, polylactide and poly(lactide-co-glycolide)) are too stiff to be suitable for engineering soft tissues. Therefore, nowadays, efforts are dedicated to develop new biodegradable elastomers. Reactive blending is a synthetic method that potentially enables to synthesize an infinite number of both block and random copolyesters by exploiting the transesterification reactions occurring at high temperatures. In this work new copolyesters of poly(butylene succinate), synthesized by reactive blending, are used to fabricate electrospun (ES) scaffolds displaying low elastic modulus. Biocompatibility of the new ES scaffolds is evaluated through embrionic rat cardiac cell culture.

The basic approach to bone tissue engineering involves the development of highly porous biodegradable 3D-scaffolds, with interconnected pore network structure for cellular in-growth, revascularization, adequate nutrition and oxygen supply. Electrospinning is a simple and cost-effective technique that enables to fabricate scaffolds, both from synthetic and natural polymers, mimicking the three-dimensional nano-scaled features of ECM. Synthetic bioresorbable polymers provide structural functionalities to the scaffold. On the other hand, natural polymers display unique bioactive properties and excellent cellular affinity. In this work we developed new electrospun scaffolds made up of poly(L)lactic acid (PLLA) fibers and Type A gelatin fibers with the aim of combining the bioactivity of gelatin together with the structural stability of PLLA in a unique scaffold. Scaffolds were prepared by concomitantly electrospinning a PLLA solution and a gelatin solution and chemical-physical properties were evaluated and related to scaffold structure and composition.

Materials with low elastic modulus (E) are expected to satisfy the required compliance of soft tissue engineering applications (E in the range 0.1-100 MPa, according to the specific native tissue). Accordingly, the interest towards new elastomeric materials with controllable degradation profiles has increased significantly in the last decade. In this work we propose reactive blending as a simple and versatile solvent-free synthetic approach to produce new biomaterials exhibiting elastomeric properties. Newly synthesized copolyether-esters are obtained by melt mixing poly(butylene succinate) (PBS) and poly(triethylene succinate) (PTES).

Development of artificial scaffolds for tissue engineering is a key area of research in the regenerative medicine field. In the in vivo microenvironment, mammalian cells are surrounded by a natural fibrillar extracellular matrix whose elements are typically organized in the nanometer scale. Progresses in nanothechnologies allowed to develop biomimetic nanofibrous scaffolds that were demonstrated to play a crucial role in controlling cell migration, proliferation, differentiation, and other complex tissue functions. This presentation will focus on the design and application of nanofibrous scaffolds fabricated through the electrospinning technology, an increasingly popular process to produce non-woven textiles composed of fibres with diameters ranging from hundreds of nanometers to several tenths of microns. The great interest towards this technology arises from the simplicity of the set-up, the cost-effectiveness of the apparatus and versatility, that allows to produce electrospun materials possessing a wide range of chemical-physical properties. In addition, it is also possible to obtain fibres from polymer blends or drug-loaded and particle-loaded fibres as well as “composite” non-woven textiles by concomitantly electrospin different materials. Another interesting advantage of electrospinning is the possibility to tune mesh micro/nano-architecture - in terms of fibre dimension, fibre surface porosity and fibre orientation - by tuning process parameters. This presentation will give an overview of frontier-research on biomimetic electrospun scaffolds and will point out some of the current industrial applications, as well as future potentiality of electrospun scaffolds in the biomedical field.

Calcium phosphate cements (CPCs) are good candidates for bone regeneration, due to their good biocompatibility, bone integration and close similarity to the mineral component of bones. In this work we investigated the possibility to introduce biodegradable polymers, namely PLLA and PLGA, into the composition of a biomimetic cement. To this aim we introduced different amounts of PLLA and PLGA nanofibers produced by the electrospinning technique into a gelatin containing alfa-tricalcium phosphate (alfa-TCP) cement. Degradability, structure, morphology and mechanical properties of the cements were analyzed as a function of composition.

Over the past six decades, engineered composite materials found wide ranging applications in land, sea and air transport vehicles, space exploration, military equipment and defense, storage, buildings and construction, chemical processing, electrical engineering, healthcare, and general engineering industries. Performance of engineered composites is tailored for an intended application by judiciously selecting the matrix and reinforcement materials, by modifying the fiber–matrix interface, and by controlling the architecture of fibers in the matrix. Most widely used reinforcement fibers are micron size diameter fibers. There is growing need for engineered composites with enhanced structural performance in newer applications as well as existing applications, which are expected to meet higher functional requirements and enhanced safety requirements. Moreover the global movement toward sustainable development is seeking engineered materials which are environmentally benign. Recently the electrospinning process has emerged as a viable industrial process to produce nanofibers from a variety of materials including naturally occurring polymers. This paper illustrates the benefits of using electrospun nanofibers in enhancing the structural performance of engineered composite materials.

In this paper we report on the characteristics of a polymer Li-ion battery based on a unique combination of innovative electrode and electrolyte materials. In particular, the electrolytic separator of this system is based on gelled membranes prepared by the electrospinning technique. Electrospinning of polymer fibers is usually realized by applying a strong electric field to a polymer solution in an appropriate solvent. Typical membranes (mats) consist of nanometre size fibers and have porosities of 56–85%. Here we describe the fabrication, physical chemistry and electrochemical properties of PVdF (poly(vinylidene difluoride))-based electrospun membranes and their use as gelled electrolyte in Li-ion battery. Moreover, we describe the performances of a battery formed by sandwiching a gelled membrane with a nanoscale engineered Sn–C based anode and a lithium nickel manganese oxide spinel cathode. The battery so obtained has an appealing performance in terms of energy density, power capability, cycle life and safety.

Medical devices and tissue engineered constructs may induce an inflammatory reaction – termed foreign body reaction (FBR) – after their in vivo implantation. Despite recent advances in material science and tissue engineering, current knowledge of the inflammatory mechanisms associated with FBR remains scanty. Electrospinning has been recognized as a scaffold fabrication technique with great potential. From a wide range of polymer solutions and melts, this technique produces continuous polymeric fibers with diameters ranging from a few nanometers to tens of microns. The possibility of controlling fiber morphology and fiber deposition pattern makes electrospinning a powerful method to fabricate tissue engineered scaffolds with a defined micro/nano-architecture in terms of fiber size and fiber orientation. Accordingly, lectrospun substrates have been used for a wide range of tissue engineering applications including neural, ardiovascular, bone, and skin tissue engineering. Despite the increased interest in electrospinning, the potential effects of electrospun scaffolds on the immune system have not been fully examined. Macrophage activation can be modulated by biomaterial topography according to the biological scale (micrometric and nanometric range). In this study we investigated the effect of fiber diameter and fiber alignment of electrospun poly(L-lactic) (PLLA) scaffolds on macrophage RAW 264.7 activation and secretion of proinflammatory cytokines and chemokines at 24 h and 7 days.

Macrophage activation can be modulated by biomaterial topography according to the biological scale (micrometric and nanometric range). In this study, we investigated the effect of fiber diameter and fiber alignment of electrospun poly(L-lactic) (PLLA) scaffolds on macrophage RAW 264.7 activation and secretion of proinflammatory cytokines and chemokines at 24 h and 7 days. Macrophages were cultured on four different types of fibrous PLLA scaffold (aligned microfibers, aligned nanofibers, random microfibers, and random nanofibers) and on PLLA film (used as a reference). Substrate topography was found to influence the immune response activated by macrophages, especially in the early inflammation stage. Secretion of proinflammatory molecules by macrophage cells was chiefly dependent on fiber diameter. In particular, nanofibrous PLLA scaffolds minimized the inflammatory response when compared with films and microfibrous scaffolds. The histological evaluation demonstrated a higher number of foreign body giant cells on the PLLA film than on the micro- and nanofibrous scaffolds. In summary, our results indicate that the diameter of electrospun PLLA fibers, rather than fiber alignment, plays a relevant role in influencing in vitro macrophage activation and secretion of proinflammatory molecules.

High molecular weight polymers that cannot be obtained by chemical routes are easily synthesized by lipase-catalyzed polymerization. Some lipases such as Candida antarctica Lipase B, when used in ring opening polymerization, allow incorporation of different monomers along the chain leading to copolymers with defined composition and microstructure. Control over microstructure is critical to the ultimate goal of tailoring the physical, mechanical, and biological properties of copolymers. Hydrophilic/hydrophobic balance can be adjusted by a suitable choice of the two monomers and of composition, leading to materials with tunable hydrolytic degradation rate for environmental and biomedical applications. Copolymers of omega-pentadecalactone with epsilon-caprolactone, valerolactone, dioxanone and trimethylenecarbonate are highly crystalline over the whole composition range, an unusual behavior due to co-crystallization of the co-monomer units. Copolyestercarbonates, copolyesteramides and polyol-containing copolyesters synthesized by lipase-catalysed polycondensation show strongly composition dependent physical properties, that can be easily tailored by composition control and cover the whole range from hard solid materials down to gluelike substances.

L’utilizzo di costrutti tessutali ingegnerizzati sviluppati in vitro e destinati ad essere impiantati in vivo per promuovere la rigenerazione di un tessuto danneggiato alimenta notevoli speranze nel campo della medicina rigenerativa e dell’ingegneria dei tessuti. Un aspetto critico nell'ingegneria dei tessuti riguarda la necessità di avvicinarsi alla tridimensionalità del contesto naturale, cioè mimare la struttura fibrillare 3D della matrice extracellulare (ECM). L’elettrofilatura è una tecnologia promettente per la fabbricazione di biomateriali in forma di fibre sub-micrometriche che richiamano l'ECM e generano per le cellule un contesto paragonabile a quello nativo. Nonostante ciò, molta ricerca rimane ancora da compiere per fabbricare scaffold con proprietà meccaniche idonee alle specifiche applicazioni. In particolare, per l’utilizzo nell’ambito dell’ingegneria del tessuto cardiaco al materiale sono richieste proprietà meccaniche elastiche per consentire l’espansione e la contrazione dello scaffold quando sottoposto a sollecitazioni cicliche in condizioni fisiologiche. Molti sforzi di ricerca sono quindi tutt’oggi dedicati allo sviluppo di nuovi polimeri con modulo elastico (E) adeguato per l’ingegneria del tessuto cardiaco. In questo lavoro si è sintetizzato un nuovo copoliestere biodegradabile a base di poli(butilene succinato) (PBS) per la realizzazione di scaffold elettrofilati che superino le limitazioni imposte dall'elevato modulo elastico dei materiali polimerici attualmente disponibili. É stata poi dimostrata la biocompatibilità dei nuovi scaffold con cellule embrionali cardiache da ratto.

Electrospun bioresorbable polymeric materials are widely used as scaffolds for tissue engineering applications. However, up to now their potential effect on the immune system has not been carefully examined. Indeed, macrophage interaction with implanted scaffold materials might lead either to cytotoxic inflammation or to constructive remodeling. In this study, in vitro evaluation of the immune response to electrospun poly(L-lactic acid) (PLLA) scaffolds with different fiber diameter and alignment has been performed by using murine macrophage cell-line RAW 264.7. Scanning electron microscopy observations showed the influence of scaffold surface topography on the macrophage morphology. In comparison to PLLA films and microfibrous scaffolds, the nanofibrous scaffolds showed less reactivity in terms of cytokines and chemokines secretion after 24 hours.

A recent advance in tissue engineering is the development of biomimetic nanofiber for tissue regeneration. Using electrospinning nanotechnology, fibrous scaffolds can be fabricated in a controllable manner from solutions of many biocompatible polymers; the final result is a scaffold displaying a 3D architecture similar to that seen in the extracellular matrix natural microenvironment. By electrospinning it is possible to produce random or aligned nanofiber mats able to influence cell behaviour that can be potentially useful in tailored clinical applications. However, in the context of heart tissue repair, few studies are reported and it is not yet established whether these biomimetic nanofiber scaffolds nay have suitable properties for promoting cell adhesion, proliferation and migration. The aim of this work is to produce electrospun nanostructured polymeric bioresorbable and biocompatible scaffolds using poly-L-lactic acid (PLLA) and to investigate the cell/scaffold interactions using H9c2 myoblast cells derived from embryonic rat heart.

Copolymers of omega-pentadecalactone (PDL) with epsylon-caprolactone, valerolactone, dioxanone and trimethylenecarbonate synthesized by biocatalysis show rather uncommon crystallization behavior, namely cocrystallization of the monomer units that leads to highly crystalline copolymers over the whole composition range. Hydrophilic/hydrophobic balance can be adjusted by a suitable choice of the comonomer and of composition, leading to materials with tunable hydrolytic degradation rate for environmental and biomedical applications. Copolyestercarbonates, copolyesteramides and polyol-containing copolyesters synthesized by lipase-catalysed polycondensation show strongly composition dependent physical properties, that can be easily tailored by composition control and cover the whole range from hard solid materials down to gluelike substances

I supporti odierni, maggiormente utilizzati per la crescita cellulare, sono realizzati con polimeri bio-compatibili e bio-riassorbibili, ma presentano una struttura interna inadeguata alla crescita veloce e controllata delle cellule. Conseguenza di ciò è la difficoltà di produrre tessuti con densità cellulare subottimale per fabbricare pseudo-tessuti idonei alla riparazione di tessuti irrimediabilmente danneggiati. In questo studio abbiamo utilizzato una nuova tecnologia basata sull'elettrofilatura per realizzare supporti polimerici a base di acido poli-L-lattico, aventi una struttura interna potenzialmente utile a ottenere una crescita cellulare più veloce e a maggiore densità. Uno degli obiettivi è la realizzazione di scaffold nano-strutturati di dimensioni eccezionalmente ridotte, in grado di imitare l’ambiente naturale del corpo umano nel quale le cellule si replicano velocemente e di fornire un adeguato supporto strutturale in seguito all’impianto nel corpo umano. La metodica utilizzata per la produzione degli scaffold è basata sulla elettrofilatura che, applicando un elevato campo elettrostatico, permette di filare un fluido polimerico fino ad ottenere fibre stirate, in seguito all’evaporazione del solvente, il cui diametro è nano-metrico dell’ordine di 0,1 micrometri, e provviste di morfologia controllabile variando opportunamente i parametri del processo. La proliferazione cellulare e l’interazione cellula-fibre di acido polilattico sono state valutate mediante saggi di bio-compatibilità col test Alamar Blue e saggi di migrazione con camera di Boyden, utilizzando fattori chemotattici quali il VEGF (fattore di crescita vascolare). L’osservazione al microscopio elettronico a scansione e su sezioni ottenute al criostato dei primi supporti elettrofilati, su cui sono state seminate cellule H9C2, mostrano una elevata affinità per le fibre di acido polilattico e una buona crescita cellulare con distribuzione delle cellule sia in superficie che nello spessore dei supporti stessi, fino a colonizzare focalmente anche il versante opposto alla superficie di semina.

The present invention relates to a process for producing polyhydroxyalkanoate oligomers and/or polymers of reduced molecular weight, which comprises reacting at least one polyhydroxyalkanoate (PHA) with at least one carbonate salt at a temperature of from 50 DEG C to 300 DEG C, preferably from 120 DEG C to 200 DEG C. The above reaction allows a controlled degradation of the PHA chains which yields oligomers and/or polymers having a controlled molecular weight, which can be modulated in view of the specific application for which the oligomers and/or polymers are intended. Moreover, during the reaction carbon dioxide evolves which produces a foamed material which can be easily processed on an industrial scale.; Additionally, the above oligomers and/or polymers, having an end-group bearing a double bond C=C, particularly a crotonate end-group for PHB, can be subjected to subsequent modifications to obtain a wide variety of functional end-groups, for instance carboxyl, carboxylate, hydroxyl, dihydroxyl, oxirane ring, halogen atom. Moreover, the low molecular weight PHAs may be used in the area of controlled delivery systems in agro-chemistry, in the cosmetic industry, in medicine in the form of nano- or microspheres, in household products and in coating systems.

Electrospinning is a very versatile technology that enables production of nanofibrous structures with morphology and fiber diameter dimensionally comparable to that of the extracellular matrix in natural tissues. For this reason electrospun scaffolds are believed to provide a better biomimetic environment than other types of porous tissue engineering scaffolds. Electrospun scaffolds offer an ideal support for cell attachment, migration, proliferation and differentiation. Non-woven mats obtained through the common electrospinning set-up, are usually characterized by random fiber orientation. A suitable design of the experimental apparatus and careful tuning of the processing parameters yield nanofibres with desired diameter and precise alignment. Nanofiber mats with specific fiber patterning may also be fabricated. This aspect is important because it is well known that the micro/nano-architecture of the scaffold may affect cell behaviour and in particular cell differentiation. The scientific community is still divided on the controversial aspect of whether or not, cells can colonize the inner regions of an electrospun mat when in vitro growth of new tissue is pursued. Many strategies have been followed by researchers to overcome the apparent limitation of efficient cell ingrowth, that is commonly attributed to too small pore size in electrospun scaffolds.In this work bioresorbable polymer scaffolds for tissue engineering are fabricated by electrospinning technology integrated with a flexible mechatronic equipment, that allows controlled and reproducible production of scaffolds with 3-D architecture tailored to specific applications. In particular, an ‘ad hoc’ collecting device allows fabrication of variously oriented and patterned fibrous structures. Composite scaffolds can also be produced by instrument implementation with multiple spinning devices. Results of in vitro cell cultures on such scaffolds provide evidence of cell colonization and penetration. In most tissue engineering applications the scaffold supporting cell growth should be bioresorbable by the host organism. Biodegradable electrospun scaffolds are made of hydrolysable polymers and must be properly designed in order to obtain bio-resorption rates tuned to the rate of tissue regeneration. In addition to their potential in tissue reconstruction, bioabsorbable nanofibrous scaffolds may also be efficiently used as drug dispensing systems for the release of bioactive molecules, such as growth factors. Electrospinning technology is very promising for the incorporation of biomolecules into fibers, thus obtaining functionalized scaffolds. The results of this work show that growth factors can be incorporated in a fiber mat during the electrospinning process without loss of bio-activity, as demonstrated by cell response upon growth factor release in the culture medium. This result confirms the versatility of the electrospinning technique.

Nanostructured electrospun three-dimensional scaffolds are used for tissue engineering applications i.e. as a guide for cellular growth. Re-absorbable polymers, such as Poly(L)lactide (PLLA) were electrospun using an "ad hoc" collecting device originally designed and realized to allow fabrication of various oriented and patterned fibrous structures. Good cell adhesion, proliferation, and colonization of the scaffold were obtained.