A miniaturized multicellular platform to mimic the 3D structure of the alveolar-capillary barrier.

Several diseases affect the alveoli, and the efficacy of medical treatments and pharmaceutical therapies is hampered by the lack of pre-clinical models able to recreate in vitro the diseases. Microfluidic devices, mimicking the key structural and compositional features of the alveoli, offer several advantages to medium and high-throughput analysis of new candidate therapies. Here, we developed an alveolus-on-a-chip recapitulating the microanatomy of the physiological tissue by including the epithelium, the fibrous interstitial layer and the capillary endothelium. A PDMS device was obtained assembling a top layer and a bottom layer obtained by replica molding. A polycaprolactone/gelatin (PCL-Gel) electrospun membrane was included within the two layers supporting the seeding of 3 cell phenotypes. Epithelial cells were grown on a fibroblast-laden collagen hydrogel located on the top side of the PCL-Gel mats while endothelial cells were seeded on the basolateral side of the membrane. The innovative design of the microfluidic device allows to replicate both cell-cell and cell-extracellular matrix interactions according to the in vivo cell arrangement along with the establishment of physiologically relevant air-liquid interface conditions. Indeed, high cell viability was confirmed for up to 10 days and the formation of a tight endothelial and epithelial barrier was assessed by immunofluorescence assays.

In Situ Forming Bioartificial Hydrogels with ROS Scavenging Capability Induced by Gallic Acid Release with Potential in Chronic Skin Wound Treatment.

In normal chronic wound healing pathways, the presence of strong and persistent inflammation states characterized by high Reactive Oxygen Species (ROS) concentrations is one of the major concerns hindering tissue regeneration. The administration of different ROS scavengers has been investigated over the years, but their effectiveness has been strongly limited by their short half-life caused by chronic wound environmental conditions. This work aimed at overcoming this criticism by formulating bioartificial hydrogels able to preserve the functionalities of the encapsulated scavenger (i.e., gallic acid-GA) and expand its therapeutic window. To this purpose, an amphiphilic poly(ether urethane) exposing -NH groups (4.5 × 1020 units/gpolymer) was first synthesized and blended with a low molecular weight hyaluronic acid. The role exerted by the solvent on system gelation mechanism and swelling capability was first studied, evidencing superior thermo-responsiveness for formulations prepared in saline solution compared to double demineralized water (ddH2O). Nevertheless, drug-loaded hydrogels were prepared in ddH2O as the best compromise to preserve GA from degradation while retaining gelation potential. GA was released with a controlled and sustained profile up to 48 h and retained its scavenger capability against hydroxyl, superoxide and 1'-diphenyl-2-picrylhydrazyl radicals at each tested time point. Moreover, the same GA amounts were able to significantly reduce intracellular ROS concentration upon oxidative stress induction. Lastly, the system was highly cytocompatible according to ISO regulation and GA-enriched extracts did not induce NIH-3T3 morphology changes.

Corrigendum: Small molecules targeting endocytic uptake and recycling pathways.

[This corrects the article DOI: 10.3389/fcell.2023.1125801.].

Development of biomimetic co-culture and tri-culture models to mimic the complex structure of the alveolar-capillary barrier.

Alveoli are the functional area of respiratory system where the gaseous exchanges take place at level of the alveolar-capillary barrier. The development of safe and effective therapeutic approaches for treating lung disease is currently limited due to the lack of realistic preclinical models for their testing and validation. In this work, tissue engineering approaches were exploited to develop a biomimetic platform that provide an appropriate mimicking of the extracellular environment and the multicellular architecture of human alveoli. Here, we propose the implementation of two biomimetic in vitro models to reproduce the features of the main anatomic portions of the physiological alveolar-capillary barrier. First, a co-culture barrier model was obtained by integrating an electrospun polycaprolactone-gelatin (PCL-Gel) membrane in a modified transwell insert (PCL-Gel TW) to mimic the alveolar basement membrane (coded as thin model). Alveolar epithelial (A549) and lung microvascular endothelial (HULEC-5a) cells were cultured on the apical and basolateral side of the PCL-Gel membrane, respectively, under physiologic air-liquid interface (ALI) conditions for 7 days. The ALI condition promoted the expression of type I and type II alveolar epithelial cell markers and the secretion of mucus in A549 cells. Increased cell viability and barrier properties in co-cultures of A549 and HULEC-5a compared to mono-cultures revealed the effectiveness of the model to reproduce in vitro physiological-relevant features of the alveolar-capillary barrier. The second portion of the alveolar-capillary barrier was developed implementing a tri-culture model (coded as thick model) including a type I collagen (COLL) hydrogel formulated to host lung fibroblasts (MRC-5). The thick barrier model was implemented by seeding HULEC-5a on the basolateral side of PCL-Gel TW and then pouring sequentially MRC-5-laden COLL hydrogel and A549 cells on the apical side of the electrospun membrane. The thick model was maintained up to 7 days at ALI and immunofluorescence staining of tight and adherent junctions demonstrated the formation of a tight barrier. Lastly, the ability of models to emulate pathological inflammatory conditions was validated by exposing the apical compartment of the PCL-Gel TW to lipopolysaccharide (LPS). The damage of A549 tight junctions, the increase of barrier permeability and IL-6 pro-inflammatory cytokine release was observed after 48 h exposure to LPS.

Lignin-Cobalt Nano-Enabled Poly(pseudo)rotaxane Supramolecular Hydrogel for Treating Chronic Wounds.

Chronic wounds (CWs) are a growing issue for the health care system. Their treatment requires a synergic approach to reduce both inflammation and the bacterial burden. In this work, a promising system for treating CWs was developed, comprising cobalt-lignin nanoparticles (NPs) embedded in a supramolecular (SM) hydrogel. First, NPs were obtained through cobalt reduction with phenolated lignin, and their antibacterial properties were tested against both Gram-negative and Gram-positive strains. The anti-inflammatory capacity of the NPs was proven through their ability to inhibit myeloperoxidase (MPO) and matrix metalloproteases (MMPs), which are enzymes involved in the inflammatory process and wound chronicity. Then, the NPs were loaded in an SM hydrogel based on a blend of α-cyclodextrin and custom-made poly(ether urethane)s. The nano-enabled hydrogel showed injectability, self-healing properties, and linear release of the loaded cargo. Moreover, the SM hydrogel's characteristics were optimized to absorb proteins when in contact with liquid, suggesting its capacity to uptake harmful enzymes from the wound exudate. These results render the developed multifunctional SM material an interesting candidate for the management of CWs.

Small molecules targeting endocytic uptake and recycling pathways.

Over the past years a growing number of studies highlighted the pivotal role of intracellular trafficking in cell physiology. Among the distinct transport itineraries connecting the endocytic system, both internalization (endocytosis) and recycling (endocytic recycling) pathways were found fundamental to ensure cellular sensing, cell-to-cell communication, cellular division, and collective cell migration in tissue specific-contexts. Consistently, the dysregulation of endocytic trafficking pathways is correlated with several human diseases including both cancers and neurodegeneration. Aimed at suppress specific intracellular trafficking routes involved in disease onset and progression, huge efforts have been made to identify small molecule inhibitors with suitable pharmacological properties for in vivo administration. Here, we review most used drugs and recently discovered small molecules able to block endocytosis and endocytic recycling pathways. We characterize such pharmacological inhibitors by emphasizing their target specificity, molecular affinity, biological activity and efficacy in both in vitro and in vivo experimental models.

Thiol-Ene Photo-Click Hydrogels with Tunable Mechanical Properties Resulting from the Exposure of Different -Ene Moieties through a Green Chemistry.

Temperature and light responsiveness are widely exploited stimuli to tune the physico-chemical properties of double network hydrogels. In this work, new amphiphilic poly(ether urethane)s bearing photo-sensitive moieties (i.e., thiol, acrylate and norbornene functionalities) were engineered by exploiting the versatility of poly(urethane) chemistry and carbodiimide-mediated green functionalization procedures. Polymers were synthesized according to optimized protocols maximizing photo-sensitive group grafting while preserving their functionality (approx. 1.0 × 1019, 2.6 × 1019 and 8.1 × 1017 thiol, acrylate and norbornene groups/gpolymer), and exploited to prepare thermo- and Vis-light-responsive thiol-ene photo-click hydrogels (18% w/v, 1:1 thiol:ene molar ratio). Green light-induced photo-curing allowed the achievement of a much more developed gel state with improved resistance to deformation (ca. 60% increase in critical deformation, γL). Triethanolamine addition as co-initiator to thiol-acrylate hydrogels improved the photo-click reaction (i.e., achievement of a better-developed gel state). Differently, L-tyrosine addition to thiol-norbornene solutions slightly hindered cross-linking, resulting in less developed gels with worse mechanical performances (~62% γL decrease). In their optimized composition, thiol-norbornene formulations resulted in prevalent elastic behavior at lower frequency compared to thiol-acrylate gels due to the formation of purely bio-orthogonal instead of heterogeneous gel networks. Our findings highlight that exploiting the same thiol-ene photo-click chemistry, a fine tuning of the gel properties is possible by reacting specific functional groups.

Design of Injectable Bioartificial Hydrogels by Green Chemistry for Mini-Invasive Applications in the Biomedical or Aesthetic Medicine Fields.

Bioartificial hydrogels are hydrophilic systems extensively studied for regenerative medicine due to the synergic combination of features of synthetic and natural polymers. Injectability is another crucial property for hydrogel mini-invasive administration. This work aimed at engineering injectable bioartificial in situ cross-linkable hydrogels by implementing green and eco-friendly approaches. Specifically, the versatile poly(ether urethane) (PEU) chemistry was exploited for the development of an amphiphilic PEU, while hyaluronic acid was selected as natural component. Both polymers were functionalized to expose thiol and catechol groups through green water-based carbodiimide-mediated grafting reactions. Functionalization was optimized to maximize grafting yield while preserving group functionality. Then, polymer miscibility was studied at the macro-, micro-, and nano-scale, suggesting the formation of hydrogen bonds among polymeric chains. All hydrogels could be injected through G21 and G18 needles in a wide temperature range (4-25 °C) and underwent sol-to-gel transition at 37 °C. The addition of an oxidizing agent to polymer solutions did not improve the gelation kinetics, while it negatively affected hydrogel stability in an aqueous environment, suggesting the occurrence of oxidation-triggered polymer degradation. In the future, the bioartificial hydrogels developed herein could find application in the biomedical and aesthetic medicine fields as injectable formulations for therapeutic agent delivery.

PDAC-on-chip for in vitro modeling of stromal and pancreatic cancer cell crosstalk.

Pancreatic ductal adenocarcinoma (PDAC) mainly develops in the head of the pancreas, within the acino-ductal unit composed of acinar and ductal cells surrounded by pancreatic stellate cells (PSCs). PSCs strongly influence the tumor microenvironment by triggering an intense stromal deposition, which plays a key role in tumor progression and limits drug perfusion. We have developed a microfluidic in vitro model recreating the in vivo tumor-stroma crosstalk to replicate the steps of PDAC evolution towards the establishment of an efficient in vitro platform for innovative therapy validation. The multilayer PDAC-on-chip was designed to culture the PDAC cells and the PSCs embedded in a type I collagen gel in the top and bottom layers, respectively. The presence of a biomimetic nanofibrous membrane in the middle of the chip permits the control of interactions between the two cell lines and the easy analysis of the effects of the crosstalk on cell behavior. First, the PDAC-stromal cell relationship was evaluated under co-culture conditions on 24-well inserts including the PCL/Gel electrospun membrane. This simplified model shows that human fibroblasts change their morphology and secrete larger amounts of IL-6 cytokines in the presence of tumor cells, confirming the activation of stromal cells under co-culture. Then, the PDAC-on-chip system was validated by demonstrating that human fibroblasts seeded in a 3D collagen matrix in the bottom microchannel also change to a myofibroblast-like shape with increased expression of α-SMA and secrete larger amounts of IL-6 cytokines. This microfluidic system is suitable for the evaluation of drug efficacy and serves as a powerful tool for understanding the early evolution steps of PDAC.

Development of an Innovative Soft Piezoresistive Biomaterial Based on the Interconnection of Elastomeric PDMS Networks and Electrically-Conductive PEDOT:PSS Sponges.

A deeply interconnected flexible transducer of polydimethylsiloxane (PDMS) and poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) was obtained as a material for the application of soft robotics. Firstly, transducers were developed by crosslinking PEDOT:PSS with 3-glycidyloxypropryl-trimethoxysilane (GPTMS) (1, 2 and 3% v/v) and using freeze-drying to obtain porous sponges. The PEDOT:PSS sponges were morphologically characterized, showing porosities mainly between 200 and 600 µm2; such surface area dimensions tend to decrease with increasing degrees of crosslinking. A stability test confirmed a good endurance for up to 28 days for the higher concentrations of the crosslinker tested. Consecutively, the sponges were electromechanically characterized, showing a repeatable and linear resistance variation by the pressure triggers within the limits of their working range (∆RR0 max = 80% for 1-2% v/v of GPTMS). The sponges containing 1% v/v of GPTMS were intertwined with a silicon elastomer to increase their elasticity and water stability. The flexible transducer obtained with this method exhibited moderately lower sensibility and repeatability than the PEDOT:PSS sponges, but the piezoresistive response remained stable under mechanical compression. Furthermore, the transducer displayed a linear behavior when stressed within the limits of its working range. Therefore, it is still valid for pressure sensing and contact detection applications. Lastly, the flexible transducer was submitted to preliminary biological tests that indicate a potential for safe, in vivo sensing applications.

Mesoporous Bioactive Glasses Incorporated into an Injectable Thermosensitive Hydrogel for Sustained Co-Release of Sr2+ Ions and N-Acetylcysteine.

An injectable delivery platform for promoting delayed bone healing has been developed by combining a thermosensitive polyurethane-based hydrogel with strontium-substituted mesoporous bioactive glasses (MBG_Sr) for the long-term and localized co-delivery of pro-osteogenic Sr2+ ions and an osteogenesis-enhancing molecule, N-Acetylcysteine (NAC). The incorporation of MBG_Sr microparticles, with a final concentration of 20 mg/mL, did not alter the overall properties of the thermosensitive hydrogel, in terms of sol-to-gel transition at a physiological-like temperature, gelation time, injectability and stability in aqueous environment at 37 °C. In particular, the hydrogel formulations (15% w/v polymer concentration) showed fast gelation in physiological conditions (1 mL underwent complete sol-to-gel transition within 3-5 min at 37 °C) and injectability in a wide range of temperatures (5-37 °C) through different needles (inner diameter in the range 0.4-1.6 mm). In addition, the MBG_Sr embedded into the hydrogel retained their full biocompatibility, and the released concentration of Sr2+ ions were effective in promoting the overexpression of pro-osteogenic genes from SAOS2 osteoblast-like cells. Finally, when incorporated into the hydrogel, the MBG_Sr loaded with NAC maintained their release properties, showing a sustained ion/drug co-delivery along 7 days, at variance with the MBG particles as such, showing a strong burst release in the first hours of soaking.

Use of Polyesters in Fused Deposition Modeling for Biomedical Applications.

In recent years, 3D printing techniques experience a growing interest in several sectors, including the biomedical one. Their main advantage resides in the possibility to obtain complex and personalized structures in a cost-effective way impossible to achieve with traditional production methods. This is especially true for fused deposition modeling (FDM), one of the most diffused 3D printing methods. The easy customization of the final products' geometry, composition, and physicochemical properties is particularly interesting for the increasingly personalized approach adopted in modern medicine. Thermoplastic polymers are the preferred choice for FDM applications, and a wide selection of biocompatible and biodegradable materials is available to this aim. Moreover, these polymers can also be easily modified before and after printing to better suit the body environment and the mechanical properties of biological tissues. This review focuses on the use of thermoplastic aliphatic polyesters for FDM applications in the biomedical field. In detail, the use of poly(ε-caprolactone), poly(lactic acid), poly(lactic-co-glycolic acid), poly(hydroxyalkanoate)s, thermoplastic poly(ester urethane)s, and their blends is thoroughly surveyed, with particular attention to their main features, applicability, and workability. The state-of-the-art is presented and current challenges in integrating the additive manufacturing technology in the medical practice are discussed.

In situ Forming Hyperbranched PEG-Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties.

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol-ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0-1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0-1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0-500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0-1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care.

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds.

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds. In this work, a thermo- and pH-responsive hydrogel (P-CHP407) was prepared from an ad hoc synthesized amphiphilic poly(ether urethane) (CHP407) exposing a significant amount of -COOH groups (8.8 ± 0.9 nmol/gpolymer). The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature (12.1 °C vs. 14.6 °C, respectively) and gelation rate than CHP407 hydrogel, as rheologically assessed. Nanoscale hydrogel characterization by Low Field NMR (LF-NMR) spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels, as further proved by Dynamic Light Scattering analyses. In addition, P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer (pH 8) (e.g., pHchange_5min = 3.76 and 1.32, respectively). Moreover, LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing -COOH groups. Lastly, the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen: delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH, suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.

Injectable supramolecular hydrogels based on custom-made poly(ether urethane)s and α-cyclodextrins as efficient delivery vehicles of curcumin.

A strategy to enhance drug effectiveness while minimizing controversial effects consists in exploiting host-guest interactions. Moreover, these phenomena can induce the self-assembly of physical hydrogels as effective tools to treat various pathologies (e.g., chronic wounds or cancer). Here, two Poloxamers®/Pluronics® (P407/F127 and P188/F68) were utilized to synthesize various LEGO-like poly(ether urethane)s (PEUs) to develop a library of tunable and injectable supramolecular hydrogels for drug delivery. Three PEUs were synthesized by chain extending Poloxamer/Pluronic with 1,6-cyclohexanedimethanol or N-Boc serinol. Other two amino-functionalized and highly responsive polymers were obtained thorough Boc-group cleavage. For hydrogel design, the spontaneous self-assembly of the poly(ethylene oxide) domains of PEUs with α-cyclodextrins was exploited to form poly(pseudo)rotaxanes (PPRs). PPR-derived channel-like crystals were characterized by X-Ray powder diffraction, Infra-Red and Proton Nuclear Magnetic Resonance spectroscopies. Cytocompatible hydrogel formulations were designed at PEU concentrations between 1% and 5% w/v and α-cyclodextrin at 10% w/v. Supramolecular gels showed good mechanical performances (storage modulus up to 20 kPa) coupled with marked thixotropic and self-healing properties (mechanical recovery over 80% within 30 s after cyclic rupture) as assessed through rheology. Hydrogels exhibited stability and high responsiveness in watery environment up to 5 days: the release of less stable components as suitable drug carriers was coupled with high swelling (doubling the content of fluids with respect to their dry mass) and shape retention. Curcumin was encapsulated into the hydrogels at high concentration (80 µg ml-1) through its complexation with α-cyclodextrins and delivery tests showed controllable and progressive release profiles up to four days.

Biomaterials Tailoring at the Nanoscale for Tissue Engineering and Advanced Therapies.

The definition of the term "biomaterial" dates back to 1991, during the 2nd Consensus Conference on the Definitions in Biomaterials organized by the European Society of Biomaterials in Chester (UK) [...].

Biocompatible Electrospun Polycaprolactone-Polyaniline Scaffold Treated with Atmospheric Plasma to Improve Hydrophilicity.

Conductive polymers (CPs) have recently been applied in the development of scaffolds for tissue engineering applications in attempt to induce additional cues able to enhance tissue growth. Polyaniline (PANI) is one of the most widely studied CPs, but it requires to be blended with other polymers in order to be processed through conventional technologies. Here, we propose the fabrication of nanofibers based on a polycaprolactone (PCL)-PANI blend obtained using electrospinning technology. An extracellular matrix-like fibrous substrate was obtained showing a good stability in the physiological environment (37 °C in PBS solution up 7 days). However, since the high hydrophobicity of the PCL-PANI mats (133.5 ± 2.2°) could negatively affect the biological response, a treatment with atmospheric plasma was applied on the nanofibrous mats, obtaining a hydrophilic surface (67.1 ± 2°). In vitro tests were performed to confirm the viability and the physiological-like morphology of human foreskin fibroblast (HFF-1) cells cultured on the plasma treated PCL-PANI nanofibrous scaffolds.

Mussel-inspired antimicrobial coating on PTFE barrier membranes for guided tissue regeneration.

Guided tissue regeneration procedures to treat periodontitis lesions making use of polytetrafluoroethylene (PTFE) membranes exhibit large variability in their surgical outcomes, due to bacterial infection following implantation. This work reports on a facile method to obtain antimicrobial coatings for such PTFE membranes, by exploiting a mussel-inspired approach andin-situformation of silver nanoparticles (AgNPs). PTFE films were initially coated with self-polymerized 3,4-dihydroxy-DL-phenylalanine (DOPA) (PTFE-DOPA), then incubated with AgNO3solution. In the presence of catechol moieties, Ag+ions reduced into Ag0, forming AgNPs of around 68 nm in the polyDOPA coating on PTFE membranes (PTFE-DOPA-Ag). The x-ray photoelectron spectroscopy, atomic force microscopy and scanning electron microscopy analyses indicated that the AgNPs were distributed quite homogeneously in the polymeric membrane. The antimicrobial ability of PTFE-DOPA-Ag membranes againstStaphylococcus aureusandEscherichia coliwas assessed.In vitrocell assay using NIH 3T3 fibroblasts showed that, although cells were adhered to PTFE-DOPA-Ag membranes, their viability and proliferation were limited demonstrating again the antibacterial activities of PTFE-DOPA-Ag membranes. This work provides proof-of-concept study of a new versatile approach for AgNPs coating, which may be easily applied to many other types of polymeric or metallic implants through exploiting the adhesive behavior of mussel-inspired coatings.

Custom-Made Poly(urethane) Coatings Improve the Mechanical Properties of Bioactive Glass Scaffolds Designed for Bone Tissue Engineering.

The replication method is a widely used technique to produce bioactive glass (BG) scaffolds mimicking trabecular bone. However, these scaffolds usually exhibit poor mechanical reliability and fast degradation, which can be improved by coating them with a polymer. In this work, we proposed the use of custom-made poly(urethane)s (PURs) as coating materials for 45S5 Bioglass®-based scaffolds. In detail, BG scaffolds were dip-coated with two PURs differing in their soft segment (poly(ε-caprolactone) or poly(ε-caprolactone)/poly(ethylene glycol) 70/30 w/w) (PCL-PUR and PCL/PEG-PUR) or PCL (control). PUR-coated scaffolds exhibited biocompatibility, high porosity (ca. 91%), and improved mechanical properties compared to BG scaffolds (2-3 fold higher compressive strength). Interestingly, in the case of PCL-PUR, compressive strength significantly increased by coating BG scaffolds with an amount of polymer approx. 40% lower compared to PCL/PEG-PUR- and PCL-coated scaffolds. On the other hand, PEG presence within PCL/PEG-PUR resulted in a fast decrease in mechanical reliability in an aqueous environment. PURs represent promising coating materials for BG scaffolds, with the additional pros of being ad-hoc customized in their physico-chemical properties. Moreover, PUR-based coatings exhibited high adherence to the BG surface, probably because of the formation of hydrogen bonds between PUR N-H groups and BG surface functionalities, which were not formed when PCL was used.