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Skin damages covering a surface larger than 4 cm(2) require a regenerative strategy based on the use of appropriate wound dressing supports to facilitate the rapid tissue replacement and efficient self-healing of the lost or damaged tissue. In the present work, A novel biomimetic approach is proposed for the design of a therapeutic porous construct made of poly(L-lactic acid) (PLLA) fabricated by thermally induced phase separation (TIPS). Biomimicry of ECM was achieved by immobilization of type I collagen through a two-step plasma treatment for wound healing. Anti-inflammatory (indomethacin)-containing polymeric nanoparticles (nps) were loaded within the porous membranes in order to minimize undesired cell response caused by post-operative inflammation. The biological response to the scaffold was analyzed by using human keratinocytes cell cultures. In this work, a promising biomimetic construct for wound healing and soft tissue regeneration with drug-release properties was fabricated since it shows (i) proper porosity, pore size, and mechanical properties, (ii) biomimicry of ECM, and (iii) therapeutic potential.

Degradable segmented poly(ether-ester-urethanes) of variable segment chemistry and content were synthesized and characterized. Polycaprolactone diol, a series of poly(ether-ester) block copolymers, and a diisocyanate giving non toxic degradation products were used to form the prepolymer. Cyclohexane dimethanol and a L-phenylalanine-based diester (Phe diester) were used as chain extenders. The influence of α-chimotrypsin on the degradation was investigated by exposing the polymers to buffer and enzyme solutions for 12 days. The SEM, SEC, and gravimetric results showed that a significant erosion of the Phe diester containing polymer compared with the control polyurethane occurred in the presence of the enzyme but not in a normal buffer solution.

A technical and economical analysis of the application of a membrane separation technique for the purification of wastewaters aimed at their reuse is described. The investigation has been carried out by treating wastewaters of a pilot plant, reproducing on a smaller scale a separation system based on ultrafiltration and reverse osmosis. Significant indications for the exploitation of this approach on the fulling industrial scale were gained during the work. The effluent from dyeing and finishing plants, after activated sludge oxidation, was treated at an 800 l/h by means of sand filtration, followed by a separation in an ultrafiltration membrane module. The last separation step, reverse osmosis at 8 bar pressure, produced a permeate (60% of the inlet flow) that, relying on the analytical screening performed, was of much better quality with respect to process water presently in use. Therefore the permeate produced can be re-used in all production steps, including the most demanding ones concerning water quality such as dyeing with light coloration. A preliminary analysis of investment and operating costs also gave encouraging indications of the economic feasibility of the approach.

Two different oxidation treatments, ozonation and electroflocculation, were experimented on a pilot scale to test their efficiency in removing polluting substances from wastewaters of textile industries. Both pilot plants used reproduced very closely a full-scale treatment in order to obtain indications about the feasibility of a transfer on industrial scale. By means of ozone treatment very high colour removal (95-99%) was achieved and treated waters were reused satisfactorily in dyeing even with light colours. This evidence despite the fact that the chemical oxygen demand of treated waters was still in a range (75-120 mg/l, a decrease up to 60%) that was usually considered to be too high for recycling purposes, especially for dyeing light colours. Treating plants working at the above-mentioned conditions should guarantee low operating costs. A biological pre-treatment and a sand filtration are absolutely essential. The transfer on industrial scale of the treatment is currently under development under an already financed European project. Electrochemical treatment showed to be very efficient in removing colour (80-100%) and chemical oxygen demand (70-90%). Moreover, a sensible decrease of chloride and sulphate ions was detected. Removal of flocculated material (post-treatment) must be, however, perfected in order to establish a correct costs-to-benefits ratio and therefore, propose an implementation of the technique on an industrial scale.

The radical polymerization of acrylic acid in the presence of poly(vinyl alcohol) as a template in aqueous solution has been studied using conductimetry, which shows template influences on the reaction rate. A comparison is made between data obtained by differential scanning calorimetry and infrared spectroscopy for poly(acrylic acid)–poly(vinyl alcohol) blends prepared either by template polymerization or by casting of the preformed polymers. Evidence for more significant interpolymer interactions in blends prepared by template polymerization than in those obtained by simple mixing is given. © 2001 Society of Chemical Industry

Bioartificial polymeric materials, based on blends of polysaccharides with synthetic polymers such as poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA), were prepared as films or hydrogels. The physico-chemical, mechanical, and biological properties of these materials were investigated by different techniques such as differential scanning calorimetry, dynamic mechanical thermal analysis, scanning electron microscopy, and in vitro release tests, with the aim of evaluating the miscibility of the polymer blends and to establish their potential applications. The results indicate that while dextran is perfectly miscible with PAA, dextran/PVA, chitosan/PVA, starch/PVA, and gellan/PVA blends behave mainly as two-phase systems, although interactions can occur between the components. Cross-linked starch/PVA films could be employed as dialysis membranes: they showed transport properties comparable to, and in some cases better than, those of currently used commercial membranes. Hydrogels based on dextran/PVA and chitosan/PVA blends could find applications as delivery systems. They appeared able to release physiological amounts of human growth hormone, offering the possibility to modulate the release of the drug by varying the content of the biological component.

The copolymerization of acrylic acid and 2-hydroxyethyl methacrylate in aqueous solution is investigated by means of High Performance Liquid Chromatography (HPLC). The reactivity ratios of the two monomers are determined by the method of Kelen-Tudos. Acrylic acid showed a preferential tendency to cross-polymerisation while 2-hydroxyethyl methacrylate tends to auto-propagate. The characterisation of the copolymer obtained in the absence of the template indicates that comonomeric units are distributed along the polymeric chain with a higher 2-hydroxyethyl methacrylate/acrylic acid ratio with respect to the feed composition. In the presence of the template (poly(N-vinylpyrrolidone)), the reaction rate and the reactivity ratio of acrylic acid increase while the same quantities decrease for the other comonomer. This experimental evidence suggests the presence of a stronger interaction betweers acrylic acid and the template. The approach used to study the system could be an useful model to investigate the mechanism of molecular recognition in aqueous (natural) environments.

Conductimetry was used for monitoring the radical polymerization of a weak electrolyte (acrylic acid) in aqueous solution and for determination of the kinetic parameters of the reaction (reaction order with respect to monomer, activation energy). The results obtained were consistent with those determined by other techniques (such as dilatometry) or expected from theory. Dilatometric and conductimetric measurements were also used to study the template polymerization of acrylic acid onto poly(N-vinylpyrrolidone). Results indicate that the reaction proceeds according to a pick-up mechanism. Complexes between poly(acrylic acid) and poly(N-vinylpyrrolidone) were always isolated in equimolar composition of the two polymers, regardless of the polymerization mixture composition. Spectroscopic evidence of the existence of strong interaction and intimate mixing of the two polymers in the complexes was found. An influence of the template molecular weight on the chain length of the forming poly(acrylic acid) was detected by means of viscometry. © 2000 Society of Chemical Industry

The radical homopolymerization of sodium acrylate in water in the presence of potassium peroxodisulphate as initiator was investigator through the use of conductimetry and dilatometry. The kinetics were monitored while varying either the monomer concentration or temperature. Initial rate and order of reaction were determined with good accuracy in a comparative way. The conductimetric method proved superior in monitoring the reaction progress at temperatures higher than 50°C, allowing the activation energy of the reaction to be determined.

Current tissue engineering (TE) strategies are aimed at the design of biomimetic scaffolds whose structural and mechanical properties are provided by biocompatible and bioresorbable synthetic polymers while the cell response is mediated by the presence of biomimetic natural polymers (proteins and polysaccharides) or short peptide sequences derived from intact extracellular matrix (ECM) proteins. The chapter reviews current approaches for the preparation of bioartificial materials with biomimetic properties for TE applications. Bulk functionalization techniques are based on blending between natural and synthetic polymers or on the synthesis of bioartificial copolymers for the preparation of biomimetic hydrogels. Surface functionalization techniques preserve the biomaterial bulk characteristics and only modify the surface properties at the micro- or nanoscale. Several surface modification techniques are available involving physical adsorption, affinity bonding, and covalent grafting. Besides the traditional approaches using natural polymers or peptides, a new trend is evolving based on scaffold functionalization with decellularized ECM.

Bi-layered scaffolds with a 0°/90° lay-down pattern were prepared by melt-extrusion additive manufacturing (AM) using a poly(ester urethane) (PU) synthesized from poly(ε-caprolactone) diol, 1,4-butandiisocyanate and l -lysine ethyl ester dihydrochloride chain extender. Rheological analysis and differential scanning calorimetry of the starting material showed that compression moulded PU films were in the molten state at a higher temperature than 155°C. The AM processing temperature was set at 155°C after verifying the absence of PU thermal degradation phenomena by isothermal thermogravimetry analysis and rheological characterization performed at 165°C. Scaffolds highly reproduced computer-aided design geometry and showed an elastomeric-like behaviour which is promising for applications in myocardial regeneration. PU scaffolds supported the adhesion and spreading of human cardiac progenitor cells (CPCs), whereas they did not stimulate CPC proliferation after 1–14 days culture time. In the future, scaffold surface functionalization with bioactive peptides/proteins will be performed to specifically guide CPC behaviour.

The synthesis and characterization of fluorescence-labelled, phase segregating block polyesterurethanes based on the known biocompatible and degradable materials poly[(R)-3-hydroxybutyric acid] (PHB), poly(e-caprolactone) (PCL), and poly[(e-caprolactone)-co-glycolide] (PCL/PGA) is described. To introduce fluorescence labels in the amorphous domains of the polymers, phenacyl 10,11-dihydroxyundecanoate (PDUA) was synthesized and copolymerized with a PHB diol, a PCL diol, and aliphatic diisocyanates. After cleavage of the protecting group (without degradation of the polymer backbone), the carboxyl group was reacted with a fluorescent amine (dansylcadaverine) in the presence of 4,6-diphenylthieno[3,4-d]-1,3-dioxol-2-one 5,5-dioxide (Steglich reagent). Also a polymer containing 13 C-labelled carboxy groups was synthesized and the labelling reaction monitored by 13 C NMR spectroscopy. To introduce fluorescence labels in the hard segment of the polymers, a new low-molecular-weight diol based on poly[(R)-hydroxybutyric acid] and containing protected carboxy groups was synthesized. After the deprotection, the carboxy groups were reacted with a fluorescent amine (dansylcadaverine) in the presence of an activating system based on dicyclohexylcarbodiimide. The labelled PHB diol was then copolymerized with a poly[(e-caprolactone)-co-glycolide] diol and an aliphatic diisocyanate. The so obtained fluorescence-labelled block polyesterurethanes are promising materials for the investigation of the biocompatibility and degradation of the corresponding, non-labelled materials (DegraPol®) by means of fluorescence-aided microscopic and spectroscopic techniques.

The synthesis and characterization of fluorescence-labelled low-molecular-weight polyesters based on known biocompatible and degradable materials such as poly[(R)-3-hydroxybutyric acid] (PHB) and poly(e-caprolactone-co-glycolide) is described. A telechelic OH-terminated poly[(R)-3-hydroxybutyric acids (M a = 2300) was modified at the end groups through esterification with BOC-glycine. After removal of the BOC protection, the so-ohtained free amino groups were conjugated with dansyl chloride to obtain dansyl-labelled end groups. No degradation of the starting material was observed during the several synthetic steps, while the crystallinity of the material was not significantly affected by the modification of the end groups. Fluorescence-labelled low-molecular-weight poly(e-caprolactone) and poly(e-caprolactone-co-glycolide) were obtained by bulk ring-opening polymerization of the corresponding cyclic monomers (e-caprolactone and diglycolide) with dansylcadaverine. Both random (amorphous) and block (semi-crystalline) copolymers were obtained depending on the presence of the catalyst (Bu 2 SnO). The so ohtained fluorescence-labelled polyesters are promising materials for the investigation of the biocompatibility and degradation of block poly(ester-urethane)s (DegraPol®) with fluorescence-aided microscopic and spectroscopic techniques.

Skin damages covering a surface larger than 4 cm(2) require a regenerative strategy based on the use of appropriate wound dressing supports to facilitate the rapid tissue replacement and efficient self-healing of the lost or damaged tissue. In the present work, A novel biomimetic approach is proposed for the design of a therapeutic porous construct made of poly(L-lactic acid) (PLLA) fabricated by thermally induced phase separation (TIPS). Biomimicry of ECM was achieved by immobilization of type I collagen through a two-step plasma treatment for wound healing. Anti-inflammatory (indomethacin)-containing polymeric nanoparticles (nps) were loaded within the porous membranes in order to minimize undesired cell response caused by post-operative inflammation. The biological response to the scaffold was analyzed by using human keratinocytes cell cultures. In this work, a promising biomimetic construct for wound healing and soft tissue regeneration with drug-release properties was fabricated since it shows (i) proper porosity, pore size, and mechanical properties, (ii) biomimicry of ECM, and (iii) therapeutic potential.

Biomaterials should be mechanically tested at both the nanoscale and macroscale under conditions simulating their working state, either in vitro or in vivo, to confirm their applicability in tissue engineering applications. In this article, polyester-urethane-based films and porous scaffolds produced by hot pressing and thermally induced phase separation respectively, were mechanically characterized at both the macroscale and nanoscale by tensile tests and indentation-type atomic force microscopy. All tests were conducted in wet state with the final aim of simulating scaffold real operating conditions. The films showed two distinct Young Moduli populations, which can be ascribed to polyurethane hard and soft segments. In the scaffold, the application of a thermal cooling gradient during phase separation was responsible for a nanoscale polymer chain organization in a preferred direction. At the macroscale, the porous matrices showed a Young Modulus of about 1.5 MPa in dry condition and 0.3 MPa in wet state. The combination of nanoscale and macroscale values as well as the aligned structure are in accordance with stiffness and structure required for scaffolds used for the regeneration of soft tissues such as muscles.

The production of efficient heart patches for myocardium repair requires the use of biomaterials with high elastomeric properties and controllable biodegradability. To fulfil these design criteria we propose biodegradable poly(ester urethanes) and poly(ether ester urethanes) from poly(ɛ-caprolactone) (PCL) and poly(ethylene glycol) (PEG) as macrodiols, 1,4-diisocyanatobutane as diisocyanate, l-Lysine Ethyl Ester and Alanine-Alanine-Lysine (AAK) as chain extenders. This peptide was used to tune biodegradability properties, since the Alanine-Alanine sequence is a target for the elastase enzyme. Enzymatic degradation tests demonstrated the feasibility of tuning biodegradability properties due to the introduction of AAK peptide in polyurethane backbone. Two formulations have been processed into porous scaffolds by Thermally-Induced Phase Separation (TIPS). Scanning Electron Microscopy micrographs revealed promising microstructures, which were characterized by stretched and unidirectional pores and mimicked the striated muscle tissue. Tensile tests showed that, although scaffolds are characterized by lower mechanical properties than films, these substrates have suitable elastomeric behaviors and elastic moduli for contractile and soft tissue regeneration. Viability tests on cardiomyocytes revealed the best cell response for dense film and porous scaffold obtained from PCL and Lysine Ethyl Ester-based polyurethane, with an increased viability for the porous substrate, which is ascribable to the morphological features of its microstructure. Future works will be addressed to study the in vivo behavior of these constructs and to confirm their applicability for myocardial tissue engineering.

The known biodegradability of poly[(R)-3-hydroxybutyric acid] (PHB) in certain biological environments had led to its proposed use as a biodegradable, biocompatible polymer. Recently, a new, rapidly biodegradable block copolymer that contains crystalline domains of PHB blocks has been synthesized. During degradation of these polymers, the PHB domains are transformed in a first step into small crystalline particles of short-chain PHB. Therefore, particles of short-chain poly[(R)-3-hydroxybutyric acid] (Mn 2300) (PHB-P), as possible degradation products, are investigated here for their effects on the viability and activation of mouse macrophages (J774), primary rat peritoneal macrophages, and mouse fibroblasts (3T3), and their biodegradation or exocytosis (or both) in these cells. Results obtained in the present study indicate that incubation of macrophages with PHB-P concentrations higher than 10 micrograms/mL were found to cause a significant decrease in the number of attached and viable cells as measured in MTT assay, and significant increase in the production levels of tumor necrosis factor-alpha (TNF-alpha) or nitric oxide (NO). At low concentrations, particles of PHB failed to induce cytotoxic effects or to activate macrophages. In addition, signs of possible biodegradation were seen in macrophages. Fibroblasts showed only limited PHB-P phagocytosis and no signs of any cellular damage or cell activation (production of collagen type I and IV, and fibronectin). Taken collectively, the present data indicate that phagocytosis of PHB-P at high concentrations ( > 10 micrograms/mL) is dose dependent and associated with cell damage in macrophages but not in fibroblasts.

The known biodegradability of poly[(R)-3-hydroxybutyric acid] (PHB) in certain biological environments has lead to its proposed use as biodegradable, biocompatible polymer. Recently, a new, rapidly biodegradable blockcopolymer has been synthesized that contains crystalline domains of PHB blocks. During degradation of these polymers, the PHB-domains are transformed in a first step into small crystalline particles of short-chain PHB. Therefore, particles of short-chain poly[(R)-3-hydroxybutyric acid] (Mn≈2300) (PHB-P), as possible degradation products, are investigated here for their effects on the viability and activation of macrophages, fibroblasts, and co-cultures of rat Kupffer cells and rat hepatocytes. Results obtained in the present study indicate that phagocytosis of particles of short-chain poly[(R)-3-hydroxybutyric acid] at high concentrations (higher than 10 μg/ml) is dosedependent and associated with cell damage in macrophages but not in fibroblasts. At low concentrations, particles of PHB-P also failed to activate macrophages and are biocompatible. Besides the PHB phagocytosis by Kupffer cells, treatment of co-cultures of Kupffer cells and hepatocytes with 1 μg PHB/ml showed neither cytotoxic (lactate dehydrogenase activity) effects nor any change in albumin secretion by hepatocytes.

The structure-property relationship of degradable polyurethanes from non toxic building blocks was studied by synthesising four different biodegradable poly(ester urethanes) from poly(epsilon-caprolactone) (PCL) dial, 1,4-diisocyanatobutane and different chain extenders. For instance, the chain extenders were an amino acid derivative diamine, an amino acid derivative diol, a cyclic diol and a custom made diamine, containing an enzymatically degradable peptide (Ala-Ala sequence). Physicochemical and morphological characterisation (SEC, DSC, DMA, AFM) was performed, showing the influence of the chain extender on the polyurethane properties. A correlation between surface domain morphologies and thermal properties was highlighted and a relationship between the biological response and surface morphologies was observed. Collecting mechanical characterisation and myoblast cell culture results together, the polyurethane synthesised with the amino acid derivative diamine resulted the most promising candidate for fabricating scaffolds supporting the regeneration of muscle tissues. (C) 2013 Elsevier Ltd. All rights reserved.

Gelatin (GL) nanofibrous matrices mimicking the complex biological structure of the natural extracellular matrix (ECM) were prepared from aqueous solutions by electrospinning technique. GL nanofibres with a diameter size of around 300nm were obtained optimising the process and solution parameters. To increase the GL stability in aqueous environment γ-glycidoxypropyltrimethoxysilane (GPTMS) was used as GL crosslinker. GPTMS crosslinking did not modify the nanofibrous matrix morphology: fibre diameter and membrane pores size were 327±45 nm and 1.64±0.37 μm, respectively. The produced GPTMS crosslinked GL nanofibres (GL/GPTMS_NF) were found to support the in vitro adhesion, proliferation and survival of neonatal olfactory bulb ensheating cells (NOBECs).

Because of their suitable bio-mechanical properties, polymeric materials, such as Poly(L-lactic acid) (PLLA), and poly (lactic-co-glycolic acid) (PLGA), are often used in the biomedical field, in particular for cardiovascular applications. Implanted materials induce several events related to the inflammatory reaction, such as macrophage adhesion and activation with following cytokine release. This work considered the effect of macrophage adhesion and related cytokine release on endothelial cells (PAOEC) proliferation and migration. Slight differences have been shown by the macrophages reaction when in contact with PLLA, PLGA, or PLLA/PLGA blend. However, these differences showed to differently enhance endothelial cells behavior in terms of wound healing. These data suggest the inflammatory reaction as a useful way to consider concerning materials biocompatibility, in order to optimize the endothelial regeneration following vascular prosthetic implants.

10.1016/j.reactfunctpolym.2013.02.005 Two different polyurethanes synthesized from two triols derived from undecenoic acid (PU1) and oleic acid (PU2) fatty acids were functionalised with Collagen type I via plasma treatment aimed at obtaining novel biomaterials with improved biological properties. Scanning Electron Microscopy, X-ray photoelectron spectroscopy, optical microscopy, colorimetric titration methods and contact angle measurements confirmed the surface changes at each stage of treatment, both in terms of morphology and chemical composition. The results for osteoblastic cells (MG63) cultured in vitro proved that PUs modified with collagen had better cytocompatibility that the control PUs. In particular, PU2 displays higher cytocompatibility.

One of the main challenges in tissue engineering/regenerative medicine (TERM) is the repair of damaged heart tissue, avoiding or minimizing ventricular remodeling which leads to ventricular dilatation and hypertrophy, sphericity increase, and functionality loss. Several approaches have been described to restore or enhance the contractility of the failing heart. One of them is based on the fabrication of 3D substrates that can be implanted in the infarcted area to provide an efficient support to the regenerative process. This review focuses on the strategies adopted to design and realize polymeric scaffolds for heart TERM. The implementation of different polymers and the design of scaffold architecture are described.

A novel biodegradable material belonging to the class of polyester-urethanes (PURs), based on poly(e-caprolactone) (PCL) blocks, was proposed as matrix-forming material for the preparation of nanoparticles by the solvent displacement method. This method has been widely applied to prepare nanoparticles with reproducible, small size with commercially available polyesters or polyester–polyether copolymers. These carriers often displayed fast and poorly controllable release rates. In response to these problems we proposed the insertion of polyesters into a more complex microstructure, such as that of polyurethanes, characterized by the alternation of hard and soft segments, in order to modulate and control the degradation rate and release profiles. PCL-based PUR (C-BC2000) was synthesized according to a two step synthesis procedure. Commercial PCL and poly(d, l lactide) (PLA) were used as controls; and paclitaxel, a potent anti-neoplastic drug, was encapsulated inside all carriers. Carriers prepared with the new material showed no intrinsic cytotoxicity (A-431 cells), with similar size in the range 211–226 nm and surface charge as the commercial controls. Moreover, C-BC2000 nanoparticles exhibited a slightly faster degradation rate, a much higher encapsulation efficiency (89 % against 24 % and 18 % for PLA and PCL, respectively) and a longer and more controlled release profile. This study highlighted the possibility to successfully employ biodegradable polyurethanes to prepare particles for controlled drug delivery, suggesting further and extensive investigation on the introduction of different PUR formulations in this field.

10.1002/jbm.a.34407 In this study, gelatin was blended to proprietary noncytotoxic polyurethanes (PU) derived from vegetable oils with different weight ratios, as material for the preparation of novel biomedical products. The PU/gelatin blends were characterized for their morphology through scanning electron microscopy. Mechanical and thermal properties, chemical interactions between components, degradation behavior, surface properties, cell adhesion, and bioactivity were investigated as a function of the protein content. Higher blend miscibility was observed for the amorphous PUs, derived from oleic acid. Properties of PU/gelatin films were strongly influenced by the concentration of gelatin in the films. Gelatin enhanced the hydrophilicity, bioactivity, and cell adhesion of PUs.

Type I collagen has been extensively exploited as a biomaterial for biomedical applications and drug delivery; however, small molecular alterations occurring during the isolation procedure and its interaction with residual bone extracellular matrix molecules or proteins might affect the overall material biocompatibility and performance. The aim of the current work is to study the potential alterations in collagen properties and organization associated with the absence of proteoglycans, which mimic pathological conditions associated with age-related diseases. A new approach for evaluating the effect of proteoglycans on the properties of isolated type I collagen from the bone matrix is described. Additional treatment with guanidine hydrochloride was introduced to remove residual proteoglycans from the collagen matrix. The properties of the isolated collagen with/without guanidine hydrochloride treatment were investigated and compared with a commercial rabbit collagen as control. We demonstrate that the absence of proteoglycans in the isolated type I collagen affects its thermal properties, the extraction into its native structure, and its ability to hydrate and self-assemble into fibers. The fine control and tuning of all these features, linked to the absence of non-collagenous proteins as proteoglycans, offer the possibility of designing new strategies and biomaterials with advanced biomimetic properties aimed at regenerating bone tissue in the case of fragility and/or defects.

Bioceramic ''shell'' scaffolds, with a morphology resembling the cancellous bone microstructure, have been recently obtained by means of a new protocol, developed with the aim to overcome the limits of the conventional foam replication technique. Because of their original microstructure, the new samples combine high porosity, permeability, and manageability. In this study, for the first time, the novel bioactive glass shell scaffolds are provided with a gelatin-based biomimetic coating to realize hybrid implants which mimic the complex morphology and structure of bone tissue. Moreover, the presence of the coating completely preserves the in vitro bioactivity of the bioactive glass samples, whose surfaces are converted into hydroxyapatite after a few days of immersion in a simulated body fluid solution (SBF).

In this work, bilayered and bioresorbable composite scaffolds are developed with mechanical and functional properties for osteochondral tissue engineering. Porous scaffolds made of gelatin (G) and bioresorbable phosphate glass (I-CEL2) with different compositions (I-CEL2/G 0/100; 30/70; 70/30 %w/w) were fabricated by freeze-drying. Samples were crosslinked using γ-glycidoxypropyltrimethoxysilane to improve mechanical strength and thermal stability. I-CEL2/G samples showed interconnected pores having an average diameter ranging from 139±5 μm for I-CEL2/G 0/100 to 116±9 μm for I-CEL2/G 70/30. GPTMS-crosslinking and the increase of I-CEL2 amount stabilized the composites to water solution, as shown by swelling tests. The compressive modulus increased by increasing I-CEL2 amount up to 7.6±0.5 MPa for I-CEL2/G 70/30.

In this work, novel strategies for the design and characterization of complex nanosized drug delivery systems for the release of different formulations were proposed and investigated. Natural or synthetic polymers, such as chitosan, poly (D,L lactide) (PLA) and proprietary polyesterurethanes, were used to prepare carriers for different applications in nanomedicine.

A new protocol, based on a modified replication method, is proposed to obtain bioactive glass scaffolds. The main feature of these samples, named "shell scaffolds", is their external surface that, like a compact and porous shell, provides both high permeability to fluids and mechanical support. In this work, two different scaffolds were prepared using the following slurry components: 59 % water, 29 % 45S5 Bioglass(®) and 12 % polyvinylic binder and 51 % water, 34 % 45S5 Bioglass(®), 10 % polyvinylic binder and 5 % polyethylene. All the proposed samples were characterized by a widespread microporosity and an interconnected macroporosity, with a total porosity of 80 % vol. After immersion in a simulated body fluid (SBF), the scaffolds showed strong ability to develop hydroxyapatite, enhanced by the high specific surface of the porous systems. Moreover preliminary biological evaluations suggested a promising role of the shell scaffolds for applications in bone tissue regeneration. As regards the mechanical behaviour, the shell scaffolds could be easily handled without damages, due to their resistant external surface. More specifically, they possessed suitable mechanical properties for bone regeneration, as proved by compression tests performed before and after immersion in SBF.

The aim of this work was the preparation and characterization of scaffolds with mechanical and functional properties able to regenerate bone. Porous scaffolds made of chitosan/gelatin (POL) blends containing different amounts of a bioactive glass (CEL2), as inorganic material stimulating biomineralization, were fabricated by freeze-drying. Foams with different compositions (CEL2/POL 0/100; 40/60; 70/30 wt %/wt) were prepared. Samples were crosslinked using genipin (GP) to improve mechanical strength and thermal stability. The scaffolds were characterized in terms of their stability in water, chemical structure, morphology, bioactivity, and mechanical behavior. Moreover, MG63 osteoblast-like cells and periostealderived stem cells were used to assess their biocompatibility. CEL2/POL samples showed interconnected pores having an average diameter ranging from 179 6 5 lm for CEL2/POL 0/ 100 to 136 6 5 lm for CEL2/POL 70/30. GP-crosslinking and the increase of CEL2 amount stabilized the composites to water solution (shown by swelling tests). In addition, the SBF soaking experiment showed a good bioactivity of the scaffold with 30 and 70 wt % CEL2. The compressive modulus increased by increasing CEL2 amount up to 2.1 6 0.1 MPa for CEL2/POL 70/30. Dynamical mechanical analysis has evidenced that composite scaffolds at low frequencies showed an increase of storage and loss modulus with increasing frequency; furthermore, a drop of E0 and E00 at 1 Hz was observed, and for higher frequencies both moduli increased again. Cells displayed a good ability to interact with the different tested scaffolds which did not modify cell metabolic activity at the analyzed points. MTT test proved only a slight difference between the two cytotypes analyzed., Contract grant sponsor: Italian Ministry of University and Research for Piergiorgio Gentile's PhD GrantContract grant sponsor: FIRB project; contract grant number: RBAP10MLK7

In this review, different barrier membranes for guided bone regeneration (GBR) are described as a useful surgical technique to enhance bone regeneration in damaged alveolar sites before performing implants and fitting other dental appliances. The GBR procedure encourages bone regeneration through cellular exclusion and avoids the invasion of epithelial and connective tissues that grow at the defective site instead of bone tissue. The barrier membrane should satisfy various properties, such as biocompatibility, non-immunogenicity, non-toxicity, and a degradation rate that is long enough to permit mechanical support during bone formation. Other characteristics such as tissue integration, nutrient transfer, space maintenance and manageability are also of interest. In this review, various non-resorbable and resorbable commercially available membranes are described, based on expanded polytetrafluoroethylene, poly(lactic acid), poly(glycolic acid) and their copolymers. The polyester-based membranes are biodegradable, permit a single-stage procedure, and have higher manageability than non-resorbable membranes; however, they have shown poor biocompatibility. In contrast, membranes based on natural materials, such as collagen, are biocompatible but are characterized by poor mechanical properties and stability due to their early degradation. Moreover, new approaches are described, such as the use of multi-layered, graft-copolymer-based and composite membranes containing osteoconductive ceramic fillers as alternatives to conventional membranes.

Scaffolds based on gelatin (G) are considered promising for tissue engineering, able to mimic the natural extracellular matrix. G drawback is its poor structural consistency in wet conditions. Therefore, crosslinking is necessary to fabricate stable G scaffolds. In this work, a comparative study between the performance of two different crosslinkers, genipin (GP) and γ-glycidoxypropyltrimethoxysilane (GPTMS), is presented. Flat membranes by solvent casting and porous crosslinked scaffolds by freeze-drying were prepared. Infrared spectroscopy and thermal analysis were applied to confirm G chain crosslinking. Moreover, GP and GPTMS increased the stability of G in aqueous media and improved the mechanical properties. Crosslinking reduced the wettability, especially in the case of G_GPTMS samples, due to the introduction of hydrophobic siloxane chains. Both G_GP and G_GPTMS scaffolds supported MG-63 osteoblast-like cell adhesion and proliferation.

A series of biostable polyurethane (PUR) formulations, including a composite containing a clay as filler, were prepared as new biomaterials for cardiovascular applications. Poly(dimethyl siloxane) and poly(tetramethylene oxide) were selected as macrodiols because of their mechanical properties and the high hydrolysis resistance they confer to PURs. 1,6-Diisocyanatohexane and 1,4-cyclohexane dimethanol were used as a diisocyanate and chain extender, respectively. The polymeric products were chemically, thermally, and mechanically characterized. Thermomechanical characterizations highlighted that some of the obtained formulations are promising materials for applications in the cardiovascular field, in particular, for the realization of annuloplastic rings in mitral valve repair. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

The preparation and characterization of PCL guides filled with a porous matrix of a freeze-dried, genipin-crosslinked gelatin sponge (GL/GP) is described. Porous guides are obtained by dip coating a rotating mandrel with a PCL/PEO blend solution followed by PEO solvent extraction. PCL/PEO 60/40 is selected as the optimal composition to obtain model porous membranes with suitable morphological properties to ensure nutrient permeation and moderate stiffness. GL/GP sponges show increased mechanical strength and water stability, compared to uncrosslinked GL sponges. GL/GP in the form of films, sponges and internal fillers support the in vitro adhesion and proliferation of Schwann like cells.

New-generation biomaterials are information-rich and incorporate biologically active components derived from Nature. The chapter reviews current approaches for the realization of biomimetic coatings for tissue engineering applications, via functionalization with bioactive molecules such as native long chains of extracellular matrix (ECM) proteins as well as short peptide sequences derived from intact ECM proteins. Biomimetic materials provide cues for cell–matrix interactions, favouring cell adhesion, proliferation, spreading, and differentiation. The recently developed scanning probe techniques for optical and spectroscopic characterization of surfaces are also described, providing advanced topographical imaging and sensitive force measurements. The spectroscopic imaging of surfaces at the nanoscale provides insight into the function and structure of biomimetic molecules and represents a tool for tailoring the surface design.

Living organisms synthesize functional materials, based on proteins and polysaccharides, using enzyme-catalyzed reactions. According to the biomimetic approach, biomaterial matrices for tissue engineering are designed to be able to mimic the properties and the functions of the extracellular matrix (ECM). In this chapter, the most significant research efforts dedicated to the study and the preparation of biomimetic materials through enzymatic modifications were reviewed. The functionalizations of different polymeric matrices obtained through the catalytic activity of two enzymes (Transglutaminase, TGase and Tyrosinase, TYRase) were discussed. Specifically, the biomimetic applications of TGase and TYRase to confer appropriate biomimetic properties to the biomaterials, such as the possibility to obtain in situ gelling hydrogels and the incorporation of bioactive molecules (growth factors) and cell-binding peptides into the scaffolds, were reviewed.

Bioartificial membranes of synthetic (poly(ethylene-co-vinyl alcohol) - EVAL, Clarene (R) ) and biological (dextran) polymers with different compositions were prepared through the phase inversion process. Dimethyl sulfoxide (DMSO) solutions of EVAL and dextran were mixed under stirring in the desired proportions and coagulated in water or DMSO (solvent)/water (non-solvent) mixture. Membrane morphologies were shown to be dependent on the synthetic and biological polymer contents and on the coagulation medium composition. Component release during solid membrane formation was evaluated by a UV method and the final composition of the bioartificial membranes established, confirming the successful entrapment of the biological component in the synthetic network. The porosity degree of the bioartificial membranes was also investigated by permeability tests and the effect of morphological characteristics on transport properties was studied. Water flux across the membranes, solute permeability and sieving coefficients were also calculated. The results revealed that the transport properties of these bioartificial membranes, obtained by the phase inversion method, could be controlled by mainly changing the preparation control parameters and the EVAL-dextran ratio.

Bone regeneration can be accelerated by localized delivery of appropriate growth factors/bio active molecules. Localized delivery can be achieved by incorporating bioactive molecules within biodegradable particulate carrier system followed by embed them in a suitable porous scaffolds. These carrier system facilitates the impregnated growth factor(s) to release at a desirable rate and concentration, and to linger at injury sites for a sufficient time to recruit progenitors and stimulate tissue healing processes. In this study, an attempt has been made to engraft the porous chitosan-gelatin scaffolds with PLGA nanoparticles for localized delivery of bioactive components. Scaffolds loaded with PLGA nanoparticles were subjected to physical and mechanical characterizations such as microarchitecture analysis, swelling, porosity, mechanical properties, dissolution studies.

The aim of this work was the preparation and characterization of new polymeric biomaterials for application in myocardial tissue engineering. The attention was firstly focused on new bioartificial polymeric systems, with the aim to combine the features of synthetic polymers with the specific cell and tissue compatibility of biopolymers. In this work, alginate, collagen, and gelatin were used as the natural component and poly(N-isopropylacrylamide) was used as the synthetic component. The characterization included morphological, topographical, and mechanical analyses, thermogravimetric characterization, infrared spectroscopy, and cell culture tests. For the biological characterization, C2C12 myoblasts were cultured on different materials and cell adhesion, proliferation, and differentiation were evaluated. The morphological, topographical, and mechanical analyses, as well as the biological characterization, were also applied to a tri-block poly(ester-ether-ester) copolymer, obtained by reaction of preformed poly(ethylene glycol) with ε-caprolactone, and a novel poly(ester urethane) obtained by using an L-lisine-derived diisocyanate, giving nontoxic degradation products. The encouraging results obtained in this work allowed us to select some of the new bioartificial polymers, the synthetic tri-block copolymer, and the polyurethane as potential good materials to prepare scaffolds for myocardial tissue engineering.

Cross-linked gelatin/hydroxyapatite/bioactive glass (G/HA/CEL2) films with different compositions (100:0:0 (G1); 30:70:0 (G2); 30:0:70 (G3); 30:35:35 (G4) (%, w/w/w)) were prepared as scaffold materials for tissue-engineering applications, particularly in the field of bone repair. A bioactive glass with 45% SiO2, 3% P2O5, 26% CaO, 7% MgO, 15% Na2O and 4% K2O molar composition was selected (CEL2). Genipin was used as a cross-linker for the gelatin component. Samples were characterized in terms of their bioactivity, thermal properties, mechanical behaviour and cell compatibility. After only 3 days of incubation in simulated body fluid (SBF) at 37 degrees C, calcium phosphate crystals precipitated on G3 and G4 surfaces, due to the high CEL2 bioactivity. Cross-linking increased the thermal stability of the gelatine component as indicated by thermal analysis (denaturation temperature was 92.3 degrees C and 97.6 degrees C for not cross-linked and cross-linked gelatin, respectively). Furthermore, tensile modulus of samples increased with increasing the inorganic phase amount (from 4.72 +/- 0.23 MPa for G1 to 6.46 +/- 0.05 MPa for G4). The adhesion and proliferation of human primary osteoblasts on composite films was evaluated. Cell viability was high with respect to the control for all samples and the presence of hydroxyapatite exerted an important role in the ability of mineralization.