Nihal Engin Vrana | Université de Strasbourg (original) (raw)

Papers by Nihal Engin Vrana

Respiratory diseases are amongst the leading causes of morbidity and mortality worldwide. There i... more Respiratory diseases are amongst the leading causes of morbidity and mortality worldwide. There is therefore significant interest in developing more efficient treatment strategies for respiratory diseases particularly where there is irreversible tissue damage and loss of function. Despite recent advances in tissue engineering and stem cell technologies the reconstruction of large defects of upper airway and similar pathologies in respiratory system remains an unmet clinical need. The complex organisation of respiratory epithelium still has not been completely recapitulated in vitro. Therefore, novel strategies for the regeneration of functional ciliated respiratory epithelium are required to address the need for the treatment of life threatening respiratory diseases as well as developing biomimetic in vitro models that can be used in drug discovery and disease modelling. This review primarily focuses on current cell based approaches including available cell sources which have shown potential for developing biomimetic models/replacements of upper respiratory epithelium. Most of the tissue engineering approaches for the development of airway epithelium use epithelial basal cells, autologous or allogenic adult stem cells, induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs) or other stromal cells to induce the organised epithelial differentiation. However, the viability and function of injected/implanted cells could suffer from the host immune response and fail to perform the desired therapeutic functions. Also, given the key role of immune cells in the respiratory epithelium in maintaining defense against external insults, the importance of immune-competency of engineered respiratory epithelia is also discussed. To this end, modulation of immune system and application of biomaterials could play an important role in improving the therapeutic value of cell based respiratory epithelium regeneration. Overall, efforts for reconstruction of functional airway epithelium can be further improved by using optimal cell sources, biomaterials and modulation of immune response. The ability to engineer organised, functional respiratory epithelium can not only provide a remedy for several debilitating diseases but also provide a strong tool for in vitro drug assessment and disease modelling.

For in-dwelling implants, controlling the biological interface is a crucial parameter to promote ... more For in-dwelling implants, controlling the biological interface is a crucial parameter to promote tissue regeneration and prevent implant failure. For this purpose, one possibility is to facilitate the establishment of the interface with cell-laden hydrogel fixed to the implant. However, for proper functioning, the stability of the hydrogel on the implant should be ensured. Modification of implant surfaces with an adhesive represents a promising strategy to promote the adhesion of cell-laden hydrogel on the implant. Herein, we developed a peptidic adhesive based on mussel foot protein (L-DOPA-L-Lysine)2-L-DOPA that can be applied directly on the surface of an implant. At physiological pH, unoxidized (L-DOPA-L-Lysine)2-L-DOPA expected to strongly adhere on metal/metal oxide surface formed only very thin coatings. Once oxidized at physiological pH, (L-DOPA-L-Lysine)2-L-DOPA forms an adhesive coating about 20 nanometers thick. In oxidized conditions, L-Lysine can adhere to metallic substrate via electrostatic interaction. Oxidized L-DOPA allows to form a coating through self-polymerization and can react with amines so this adhesive can be used to fix ECM based materials on implant surfaces through the reaction of quinones with amino groups. Hence, a stable interface between a soft gelatin hydrogel and metallic surfaces was achieved and the strength of adhesion was investigated. We have shown that the adhesive is non-cytotoxic to encapsulated cells and enabled the adhesion of gelatin soft hydrogels for 21 days on metallic substrates in liquid conditions. The adhesion properties of this anchoring peptide was quantified by a 180° peeling test. Utilization of a biomimetic adhesive interface is an important tool for the application of cell-laden hydrogels to metallic implant surfaces as hydrogel/implant interface can be ensured without relying on the properties of the deposited biomaterials.

In many biomedical applications, titanium forms an interface with tissues, which is crucial to en... more In many biomedical applications, titanium forms an interface with tissues, which is crucial to ensure its long-term stability and safety. In order to exert control over this process, titanium implants have been treated with various methods that induce physicochemical changes at nano and microscales. In the past 20 years, most of the studies have been conducted to see the effect of topographical and physicochemical changes of titanium surface after surface treatments on cells behavior and bacteria adhesion. In this review, we will first briefly present some of these surface treatments either chemical or physical and we explain the biological responses to titanium with a specific focus on adverse immune reactions. More recently, a new trend has emerged in titanium surface science with a focus on the crystalline phase of titanium dioxide and the associated biological responses. In these recent studies, rutile and anatase are the major two polymorphs used for biomedical applications. In the second part of this review, we consider this emerging topic of the control of the crystalline phase of titanium and discuss its potential biological impacts. More in-depth analysis of treatment-related surface crystalline changes can significantly improve the control over titanium/host tissue interface and can result in considerable decreases in implant-related complications, which is currently a big burden on the healthcare system.

Adverse immune reactions prevent clinical translation of numerous implantable devices and materia... more Adverse immune reactions prevent clinical translation of numerous implantable devices and materials. Although inflammation is an essential part of tissue regeneration, chronic inflammation ultimately leads to implant failure. In particular, macrophage polarity steers the microenvironment toward inflammation or wound healing via the induction of M1 and M2 macrophages, respectively. Here, this paper demonstrates that macrophage polarity within biomaterials can be controlled through integrin-mediated interactions between human monocytic THP-1 cells and collagen-derived matrix. Surface marker, gene expression, biochemical, and cytokine profiling consistently indicate that THP-1 cells within a biomaterial lacking cell attachment motifs yield proinflammatory M1 macrophages, whereas biomaterials with attachment sites in the presence of interleukin-4 (IL-4) induce an anti-inflammatory M2-like phenotype and propagate the effect of IL-4 in induction of M2-like macrophages. Importantly, integrin α2β1 plays a pivotal role as its inhibition blocks the induction of M2 macrophages. The influence of the microenvironment of the biomaterial over macrophage polarity is further confirmed by its ability to modulate the effect of IL-4 and lipopolysaccharide, which are potent inducers of M2 or M1 phenotypes, respectively. Thus, this study represents a novel, versatile, and effective strategy to steer macrophage polarity through integrin-mediated 3D microenvironment for biomaterial-based programming.

Smart Technologies, IEEE EUROCON 2017-17th International Conference on

Many important aspects of medical field relies on acquisition of high-resolution images and then ... more Many important aspects of medical field relies on acquisition of high-resolution images and then careful development of algorithms that would facilitate unsupervised analysis of these images. While advances in medicine and biology experiments and data gathering is growing more and more every day, the need to read in real time this data and to get the desired information is increasing too. To manage all the needs that scientists have in order to get the real time information many image processing algorithms are used. The algorithms may be adapted based on the system of interest, and often the most challenging feature of the images may be used to facilitate a better analysis of the image. Herein, we developed an image analysis algorithm for quantification of cellular shape and size on micropatterned surfaces (gelatin) as a means to predict their phenotypic behavior. We have two conditions: i) individual dispersal of the cells on the surfaces, and ii) the clustering of cells in small and large patches. The analysis of the former condition, that includes counting and determining of the cells' area, relies on successful segmentation. In the second setting where clustering of cells is favoured, individual cell segmentation and counting becomes more challenging and we determine the relative area that is covered by the cells. Direct image processing techniques can provide a reasonable qualitative picture of the behavior of the cells that sit on the regularly micropatterned surfaces that create a challenging background for the segmentation. Employing filters in both spatial and frequency (reciprocal) domain enabled a higher quantitative analysis of the cell behavior. Our method uses the periodic repetition of the patterns to distinguish the cellular features from the topography of the substrate, which can be generalized for the analysis of cellular metrics on micropatterned surfaces.

The success of tissue engineering strategy is strongly related to the inflammatory response, main... more The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, we developed an in-vitro model of interaction between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, Naive THP-1 monocytes, endothelial cells, and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. In order to mimic resident macrophages, THP-1 cells were encapsulated in the presence or absence of IL-4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in secretion of both pro and anti-inflammatory cytokines compared to M2 stimulation. We demonstrated that there is a distinct effect of encapsulated macrophages on the behavior of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.

Macrophages are master regulators of immune responses toward implanted 19 biomaterials. The activ... more Macrophages are master regulators of immune responses toward implanted 19 biomaterials. The activation state adopted by macrophages in response to biomaterials 20 determines their own phenotype and function as well as those of other resident and 21 infiltrating immune and nonimmune cells in the area. A wide spectrum of macrophage 22 activation states exists, with M1 (pro-inflammatory) and M2 (anti-inflammatory) 23 representing either ends of the spectrum. In biomaterials research, cell-instructive surfaces 24 that favor or induce M2 macrophages have been considered as beneficial due to the anti-25 inflammatory and pro-regenerative properties of these cells. In this study, we used a gelatin 26 methacryloyl (GelMA) hydrogel platform to determine whether micropatterned surfaces can 27 modulate the phenotype and function of human macrophages. The effect of microgrooves/ 28 ridges and micropillars on macrophage phenotype, function, and gene expression profile 29 were assessed using conventional methods (morphology, cytokine profile, surface marker 30 expression, phagocytosis) and gene microarrays. Our results demonstrated that micro-31 patterns did induce distinct gene expression profiles in human macrophages cultured on 32 microgrooves/ridges and micropillars. Significant changes were observed in genes related to primary metabolic processes such as 33 transcription, translation, protein trafficking, DNA repair, and cell survival. However, interestingly conventional phenotyping 34 methods, relying on surface marker expression and cytokine profile, were not able to distinguish between the different conditions, 35 and indicated no clear shift in cell activation toward an M1 or M2 phenotypes. This highlights the limitations of studying the 36 effect of different physicochemical conditions on macrophages by solely relying on conventional markers that are primarily 37 developed to differentiate between cytokine polarized M1 and M2 macrophages. We therefore, propose the adoption of unbiased 38 screening methods in determining macrophage responses to biomaterials. Our data clearly show that the exclusive use of 39 conventional markers and methods for determining macrophage activation status could lead to missed opportunities for 40 understanding and exploiting macrophage responses to biomaterials. 41

Adverse immune reactions to implanted devices can seriously hamper the efficacy of implants. Mono... more Adverse immune reactions to implanted devices can seriously hamper the efficacy of implants. Monocyte derived macrophages play a crucial role in both initiation and resolution of the inflammatory response toward foreign bodies. As the surface microtopography is shown to exert significant effects on cell phenotype, it is hypothesized that the presence of micropatterns on implant/medical device surfaces can attenuate the immune response. To this end, enzymatically crosslinked micropatterned gelatin films of varying groove widths (2, 5, 10, 20, and 40 µm) are tested for their effect on incoming monocyte behavior. In order to distinguish the effect of cytokine microenvironment on pattern presence, monocytes are seeded on micropatterned films in normal culture medium or M1/M2 inducing media and their morphology and cytokine secretions are observed for 6 d. The presence of the patterns induces microenvironment-specific changes on the secretions of the attached cells and also on their size. IL-1ß, IL-4, IL-12, TNF-α, and CCL-18 secretions are significantly affected particularly in M1 induction media by pattern presence. It is demonstrated for the first time that micropatterned surfaces can be used to control the initial attachment and cytokine secretion of incoming macrophages if they are linked with a polarization inducing cytokine microenvironment.

Objective: The objective of this study was to investigate the reproducibility, mechanical integri... more Objective: The objective of this study was to investigate the reproducibility, mechanical integrity, surface characteristics and corrosion behavior of nanotubular (NT) titanium oxide arrays in comparison with a novel nano-pitted (NP) anodic film. Methods: Surface treatment processes were developed to grow homogenous NT and NP anodic films on the surface of grade 2 titanium discs and dental implants. The effect of process parameters on the surface characteristics and reproducibility of the anodic films was investigated and optimized. The mechanical integrity of the NT and NP anodic films were investigated by scanning electron microscopy, surface roughness measurement, scratch resistance and screwing tests, while the chemical and physicochemical properties were investigated in corrosion tests, contact angle measurement and X-ray photoelectron spectroscopy (XPS). Results and discussion: The growth of NT anodic films was highly affected by process parameters, especially by temperature, and they were apt to corrosion and exfoliation. In contrast, the anodic growth of NP film showed high reproducibility even on the surface of 3-dimensional screw dental implants and they did not show signs of corrosion and exfoliation. The underlying reason of the difference in the tendency for exfoliation of the NT and NP anodic films is unclear; however the XPS analysis revealed fluorine dopants in a magnitude larger concentration on NT anodic film than on NP surface, which was identified as a possible causative. Concerning other surface characteristics that are supposed to affect the biological behavior of titanium implants, surface roughness values were found to be similar, whereas considerable differences were revealed in the wettability of the NT and NP anodic films. Conclusion: Our findings suggest that the applicability of NT anodic films on the surface of titanium bone implants may be limited because of mechanical considerations. In contrast, it is worth to consider the applicability of nano-pitted anodic films over nanotubular arrays for the enhancement of the biological properties of titanium implants.

Coatings with antimicrobial properties are garnering interest to prevent implant-associated infec... more Coatings with antimicrobial properties are garnering interest to prevent implant-associated infections. Recently, we showed that poly(arginine)/hyaluronic acid (PAR/HA) multilayers built with PAR chains constituted from 30 arginine residues (PAR30) have strong antimicrobial properties through a contact-killing mechanism. This property is due to the ability of PAR30 chains, when associated with HA, to diffuse in the multilayer. Here, we investigate the effect of the nature of the polyanion on the antimicrobial activity of (PAR30/polyanion) multilayers. Four poly-saccharides, one polypeptide, and one synthetic polyelectrolyte are investigated. Surprisingly, only HA leads to films with antimicrobial character. We relate this property to the strong diffusion capacity of PAR30 chains in (PAR30/HA) multilayers compared to their diffusion ability in the other (PAR30/polyanion) films. Through isothermal microcalorimetry experiments, we also demonstrate that interactions in solutions of PAR30 chains with the different polyanions are characterized by a negative reaction enthalpy for all of the investigated polyanions except for HA, where the enthalpy of reaction is positive. Moreover, the molecular weight of HA is not a key parameter for the diffusion ability of PAR chains or for the bioactivity of the film. These results constitute an important step toward the establishment of rules to design contact-killing antimicrobial polyelectrolyte multilayers.

Delivery of growth factors is an indispensable part of tissue engineering. Here, we describe a de... more Delivery of growth factors is an indispensable part of tissue engineering. Here, we describe a detachable membrane-based release system composed of extracellular matrix components that can be attached to hydrogels to achieve directional release of bioactive molecules. This way, the release of cytokines/growth factors can be started at a desired point of tissue maturation or directly in vivo. As a model, we develop thin films of an interpenetrating network of doublecross linked gelatin and hyaluronic acid derivatives. The use of the auxiliary release system with vascular endothelial growth factor results in extensive sprouting by encapsulated vascular endothelial cells. The presence of the release system with interleukin-4 results in clustering of encapsulated macrophages with a significant decrease in M1 macrophages (proinflammatory). This system can be used in conjunction with three-dimensional structures as an auxiliary system to control artificial tissue maturation and growth.

The immediate tissue microenvironment of implanted biomedical devices and engineered tissues is h... more The immediate tissue microenvironment of implanted biomedical devices and engineered tissues is highly influential on their long term fate and efficacy. The creation of a long-term anti-inflammatory microenvironment around implants and artificial tissues can facilitate their integration. Macrophages are highly plastic cells that define the tissue reactions on the implanted material. Local control of macrophage phenotype by long-term fixation of their healing activities and suppression of inflammatory reactions are required to improve implant acceptance. Herein, we describe the development of a cytokine cocktail (M2Ct) that induces stable M2-like macrophage phenotype with significantly decreased pro-inflammatory cytokine and increased anti-inflammatory cytokine secretion profile. The positive effect of the M2Ct was shown in an in vitro wound healing model; where M2Ct facilitated wound closure by human fibroblasts in co-culture conditions. Using a model for induction of inflammation by LPS we have shown that the M2Ct phenotype is stable for 12 days. However, in the absence of M2Ct in the medium macrophages underwent rapid pro-inflammatory re-programming upon IFNg stimulation. Therefore, loading and release of the cytokine cocktail from a self-standing, transferable Gelatin/Tyraminated Hyaluronic acid based release system was developed to stabilize macrophage phenotype for in vivo application in implantation and tissue engineering. The M2Ct cytokine cocktail retained its anti-inflammatory activity in controlled release conditions. Our data indicate that the direct application of a potent M2 inducing cytokine cocktail in a transferable release system can significantly improve the long term functionality of biomedical devices by decreasing pro-inflammatory cytokine secretion and increasing the rate of wound healing.
Statement of Significance

Uncontrollable activation of macrophages in the microenvironment of implants and engineered tissues is a significant problem leading to poor integration of implants and artificial tissues. In the current manuscript we demonstrate that self-standing, transferable gelatin/tyraminated hyaluronic acid based thin films are perspective tools for controlled release of anti-inflammatory cytokine combinations and can be used to down-modulate macrophage activation on implant surfaces. We also show that optimized cytokine cocktail consisting of IL4/IL10/TGFβ1 (M2Ct) induces long-term anti-inflammatory and pro-healing phenotype in human primary monocyte-derived macrophages. This cocktail formulation could be loaded on gelatin/tyraminated films and promoted favorable M2-like macrophage phenotype with low responsiveness to pro-inflammatory stimuli. Such self-standing release systems can be used for prolonged local control of macrophage phenotype upon implantation.

Journal of Biomaterials Science, Polymer Edition, 2007

In this study, a highly porous collagen-based biodegradable scaffold was developed as an alternat... more In this study, a highly porous collagen-based biodegradable scaffold was developed as an alternative to synthetic, non-degradable corneal implants. The developed method involved lyophilization and subsequent stabilization through N-ethyl-N&amp;#39;-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) cross-linking to yield longer lasting, porous scaffolds with a thickness similar to that of native cornea (500 microm). For collagen-based scaffolds, cross-linking is essential; however, it has direct effects on physical characteristics crucial for optimum cell behavior. Hence, the effect of cross-linking was studied by examining the influence of cross-linking on pore size distribution, bulk porosity and average pore size. After seeding the foam with human corneal keratocytes, cell proliferation, cell penetration into the scaffold and ECM production within the scaffold were studied. After a month of culture microscopical and immunohistochemical examinations showed that the foam structure did not undergo any significant loss of integrity, and the human corneal keratocytes populated the scaffold with cells migrating both longitudinally and laterally, and secreted some of the main constituents of the corneal ECM, namely collagen types I, V and VI. The foams had a layer of lower porosity (skin layer) both at the top and the bottom. Foams had an optimal porosity (93.6%), average pore size (67.7 microm), and chemistry for cell attachment and proliferation. They also had a sufficiently rapid degradation rate (73.6+/-1.1% in 4 weeks) and could be produced at a thickness close to that of the natural corneal stroma. Cells were seeded at the top surface of the foams and their numbers there was higher than the rest, basically due to the presence of the skin layer. This is considered to be an advantage when epithelial cells need to be seeded for the construction of hemi or full thickness cornea.

Organ loss due to late-stage cancer is a heavy burden on both the patient and the health care sys... more Organ loss due to late-stage cancer is a heavy burden on both the patient and the health care system. Total laryngectomy in patients with advanced laryngeal or hypopharyngeal carcinoma is lifesaving,1 but it entails a substantial loss of quality of life because of altered physiological functions and a sense of mutilation. We designed an artificial larynx that can replace lost laryngeal functions. We first implanted an artificial larynx in a patient in 2012. Here we present the case of a patient who received an ENTegral artificial larynx in 2015 after total laryngectomy and underwent 16 months of follow-up.

Abstract: Stacked, lamellar constructs comprised of, synthetic or natural, polymeric membrane str... more Abstract: Stacked, lamellar constructs comprised of, synthetic or natural, polymeric membrane structures which are brought together to form 3D scaffolds for biomaterial and guided tissue engineering applications have been developed. Each layer can have 2D or 3D nano and micro topographical features similar to or different than each other which can be arranged during the construction of each lamellae and their orientation can be adjusted during construction phase of the 3D structure. Such a construct was utilized in the ...

Biomaterials, 2007

Collagen-based micropatterned films were seeded with human corneal keratocyte and epithelial cell... more Collagen-based micropatterned films were seeded with human corneal keratocyte and epithelial cells to study their mechanical properties as tissue engineering substrates. The patterns were in the form of parallel channels with slanted walls. Influence of cell presence, type and growth on the mechanical properties of the films was investigated. Unseeded films showed gradual strength reduction from an initial value of 0.046 N/mm, possibly due to degradation, down to 0.03270.012 N/mm in 2 weeks. Keratocyte growth was found to significantly improve the mechanical behavior of the films upon 1 week of incubation (0.06770.017 N/mm) and the improvement continued gradually over the next 2 weeks. Films seeded with D407 retinal pigment epithelial cells, on the other hand, experienced a decrease (0.02370.011 N/mm), followed by a slight increase in mechanical properties in the 21-day period. A steady increase in the number of keratocytes along the channels, cytoskeleton alignment and extracellular matrix (ECM) secretion restricted to the channels was observed. Increase in strength observed with keratocytes and, to a lesser extent, with the epithelial cells can be attributed to directional ECM synthesis and the orientation of the cells and their cytoskeleton which contribute to the strength in the direction of the channels. This study showed that cell, especially keratocyte, presence compensates for the degradation of collagen films and improve the overall mechanical properties of the engineered tissue. r

Metallic implants are widely used in orthopaedic and orthodontic applications. However, generally... more Metallic implants are widely used in orthopaedic and orthodontic applications. However, generally surface treatment of the metallic surfaces is necessary to render them more biologically active. Herein, we describe a direct write printing method to modify metallic implant surfaces with biocompatible polymers with microscale precision. Application of polymeric micropatterns on metallic implant surfaces can (i) improve their interaction with the host tissue, (ii) enable the delivery of growth factors, antibiotics, anti-inflammatory cytokines etc from the implant surface and (iii) can control the immune responses to the implant via controlling the attachment of immune cells, such as macrophages. Surface patterns with a resolution of less than 50 μm can be created using an electro hydrodynamic (EHD) printing, a template-free and single-step process. We present a revised EHD printing method for the deposition of parallel strips of photocrosslinkable, cell adhesive polymeric composites with spacing of around 20 μm onto medical grade titanium substrates. Optimization of voltage, feeding rate and collection speed resulted in regular structures via very rapid movement of the grounded rotating collector driven to equivalent of the linear surface speed of above 100 cm s−1. In the experimental part a mixture of chemically modified PEG /gelatin was deposited onto a conductive titanium substrate with different surface pretreatments with an area of 400 mm2. Acid etched or UV treated titanium surfaces improved the stability of the printed structures. Polymeric lines induced temporary orientation of human monocytes (THP-1) and induced a thicker cell multilayer formation by 3T3 fibroblasts (p < 0.05). Staining of the monocytes for M1(CD80) and M2 (CD206) macrophage markers on the patterned surface showed mixed populations with higher anti-inflammatory cytokine secretion compared to tissue culture plastic control. The results demonstrate the suitability of this method for the preparation of biomaterials with structured surfaces on large areas and with desired chemical composition.

BioMed Research International, 2014

The number of nosocomial infections related to implants and medical devices increase alarmingly ... more The number of nosocomial infections related to
implants and medical devices increase alarmingly worldwide.
New strategies based on the design of antimicrobial coatings
are required to prevent such infections. Polyelectrolyte
“multilayer” films constitute a powerful tool for nanoscale
surface functionalization which allows addressing this issue. By
investigating films built up with poly(arginine) (PAR) of
various chain lengths (10, 30, 100, and 200 residues) and
hyaluronic acid (HA), we demonstrate that exclusively films
constructed with poly(arginine) composed of 30 residues
(PAR30) acquire a strong antimicrobial activity against Gram-
positive and Gram-negative pathogenic bacteria associated
with infections of medical devices. This chain-size effect is extremely striking and is the first example reported where the length of
the polyelectrolytes played a key-role in the functionality of the films. Moreover, this unexpected functionality of nanolayered
polypeptide/polysaccharide PAR30/HA films occurs without adding any specific antimicrobial agent, such as antibiotics or
antimicrobial peptides. PAR30/HA film inhibits bacteria through a contact-killing mechanism due to the presence of mobile
PAR30 chains. These chains are assumed to diffuse toward the interface, where they interact with the bacteria with the consequence of killing them. This new coating with unique properties based on the association of a homopolypeptide of 30 residues with a polysaccharide constitutes a simple system to prevent implant-related infections with a reasonable production cost.

Smart Technologies, IEEE EUROCON 2017-17th International Conference on

Journal of Biomaterials Science, Polymer Edition, 2007

Biomaterials, 2007

BioMed Research International, 2014

As tissue engineering, real-time biosensors, and lab-on-a-chip applications for monitoring and mo... more As tissue engineering, real-time biosensors, and lab-on-a-chip applications for monitoring and modeling become more widespread, it is important to provide a concise overview of theoretical and practical foundations of this field. This book presents readers with a better understanding of the underlying scientific principles in the areas of tissue engineering, biosensors, and implants. By focusing on the specific interaction of cells with these various interfaces, it is possible to highlight current developments as well as their practical and clinical applications.

Poly(vinyl alcohol) cryogels are physically cross-linked hydrogels formed through one or more fre... more Poly(vinyl alcohol) cryogels are physically cross-linked hydrogels formed through one or more freezing
and thawing cycles with an aqueous polymer solution. As well as being highly biocompatible, the resulting
gels have attractive characteristics in terms of tissue mimicking mechanical properties. They also possess
the added benefi t that these properties can be fi ne-tuned through material parameters (such as solution
concentration) and processing properties (such as number of freeze–thaw cycles or rate of thawing). There
has been signifi cant effort to take advantage of the inherent potential of these gels for tissue replacement
applications through cryogelation process enhancements, formation of composite gels, and the development
of cell encapsulation protocols. These developments can modify pore architecture and alignment, enhance
cell attachment, and bioactivity or enable the formation of cell laden cryogels as part of the freezing and
thawing process. This entry reviews each of these areas, making particular reference to areas of application
for cardiovascular and orthopedic implant and tissue engineering therapies, and also to diabetes treatment.

Tissue engineering has emerged as a growing field for repair and regeneration of damaged organs ... more Tissue engineering has emerged as a growing field for repair and
regeneration of damaged organs and tissues. The development
of biomimetic scaffolds plays a crucial role in engineering tissue
constructs by regulating cellular responses. Three dimensional (3D) scaffolds serve as a temporary extracellular matrix (ECM) that provide an environment with a desirable mechanical support for cell growth and tissue regeneration. Scaffolds that mimic the characteristics of natural ECM is ideal for tissue engineering as they direct different cellular behaviors including cell migration, adhesion, proliferation, and differentiation. The architecture, physical characteristics, and biochemical properties of scaffolds play important roles in regulating cellular functions and subsequent tissue maturation. In this chapter, various aspects in the design of biomimetic scaffolds are discussed.
The approaches developed for the modification of both surface
and bulk properties of biomaterials are explained. These strategies include micro- or nanopatterning, 3D construction of scaffolds, and bulk modification such as rapid prototyping (RP), electrospinning, and phase separation. The effects of biophysical signals (e.g., mechanical stiffness and pore architecture) on cell behavior and differentiation are then elucidated. Finally, biochemical biomimicry in scaffolds based on incorporation of biomolecules such as proteins and growth factors are discussed.

The invention relates to tubular prostheses or implants having increased protein adsorption on th... more The invention relates to tubular prostheses or implants having increased protein adsorption on the external surface and not on the internal surface, and to the process of obtaining such prosthesis by specific surface treatments on localized parts of said prosthesis.