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This study reports the investigation of a degraded polyethylene insert retrieved after the catastrophic failure of a mobile bearing knee implant, occurred after a traumatic event and leading to a late revision. Understanding wear mechanisms of polyethylene components is important to improve the implants for joint replacement. This model of unicompartmental arthroplasty, due to its mobile, congruent insert and design, has the potential to attain low rates of wear, leading to an improved survival of the prosthesis over fixed-bearing knee implants. During the surgical technique, however, it is critical to avoid any source of impingement or incongruent articulation, as this are associated with increased rates of polyethylene wear and may contribute to the early necessity for revision surgery. The investigated insert presented a macroscopic fragmentation, surface and bulk defects and debris. Characterization of the retrieved polyethylene implant fragments was performed by macroscopic examination, by scanning electron microscopy and Fourier transform infrared spectroscopy. Due to a systematic retrieval analysis according to current standards, we can question that, in our case, third body wear is rarely pure bone or pure cement debris related but a combination of the two mentioned. The combination enhanced contribution of polyethylene debris in severe wear initiation and progression. Complete examination of the explants exhibiting breakage or severe wear may help in understanding pathogenic ways of failure in unicompartmental knee.

Manufacturing of three-dimensional scaffolds with multiple levels of porosity are an advantage in tissue regeneration approaches to influence cell behavior. Three-dimensional scaffolds with surface roughness and intra-filament open porosity were successfully fabricated by additive manufacturing combined with chemical foaming and porogen leaching without the need of toxic solvents. The decomposition of sodium citrate, a chemical blowing agent generated pores within the scaffold filaments, which were interconnected and opened to the external environment by leaching of a water-soluble sacrificial phase, as confirmed by micro-CT and buoyancy measurements. The additional porosity did not result in lower elastic modulus, but in higher strain at maximum load, i.e. scaffold ductility. Human mesenchymal stromal cells cultured for 24 h adhered in greater numbers on these scaffolds when compared to plain additive-manufactured ones, irrespectively of the scaffold pre-treatment method. Additionally, they showed a more spread and random morphology, which is known to influence cell fate. Cells cultured for a longer period exhibited enhanced metabolic activity while secreting higher osteogenic markers after 7 days in culture. STATEMENT OF SIGNIFICANCE: : Inspired by the function of hierarchical cellular structures in natural materials, this work elucidates the development of scaffolds with multiscale porosity by combining in-situ foaming in additive manufacturing and successive porogen leaching. The resulting scaffolds displayed enhanced mechanical 0toughness and multiscale pore network interconnectivity, combined with early differentiation of adult mesenchymal stromal cells into the osteogenic lineage.

The main function of articular cartilage is to provide a low friction surface and protect the underlying subchondral bone. The extracellular matrix composition of articular cartilage mainly consists of glycosaminoglycans and collagen type II. Specifically the collagen type II organization has a characteristic organization in three distinct zones; (1) the superficial zone which has collagen fibers oriented parallel to the surface, (2) the intermediate zone where there is no predominant orientation, and (3) the deep zone which shows a high orientation with fibers perpendicular to the underlying bone. Collagen type II fibers in these 3 zones take an arch-like organization that can be mimicked with segments of a hypotrochoidal curve. In this study, a script was developed that allowed the fabrication of scaffolds with a hypotrochoidal design. This design was investigated and compared to a regular 0-90 woodpile design. The results showed that the hypotrochoidal design was successfully fabricated. Micro-CT analyses divided the areas of the scaffold in their distinct zones. In addition, the mechanical analyses revealed that the hypotrochoidal design had a lower component Young’s modulus while the toughness and strain at yield were higher compared to the woodpile design. Fatigue tests showed that the hypotrochoidal design lost more energy per cycle due to the damping effect of the unique microarchitecture. Finite element analyses revealed that the hypotrochoidal design had an improved stress distribution compared to the 0-90 woodpile design due to the lower component stiffness. In addition, data from cell culture under dynamic stimulation demonstrated that the collagen type II deposition was improved in the hypotrochoidal design. Finally, Alcian blue staining revealed that the areas where the stress was higher during the stimulation produced more glycosaminoglycans. Our results highlight a new and simple scaffold design based on hypotrochoidal curves that could be used for cartilage tissue engineering.

Monoaldehydes, due to natural origin and therapeutic activity, have attracted great attention for their ability to crosslink chitosan hydrogels for biomedical applications. However, most studies have focused on single-component hydrogels. In this work, chitosan-based hydrogels, crosslinked for the first time with 2,3,4-trihydroxybenzaldehyde (THBA), were modified with pectin (PC), bioactive glass (BG), and rosmarinic acid (RA). All of these were not only involved in the crosslinking, but also modulated properties or imparted completely new ones. THBA functioned as a crosslinker, resulting in improved mechanical properties, high swelling capacity and delayed degradation and also imparted high antioxidant activity and antiproliferative effect on cancer cells without cytotoxicity for normal cells. Hydrogels containing PC showed enhanced mechanical strength, while the combination with BG gave improved stability in PBS. All hydrogels modified with BG exhibited the ability to mineralise in SBF. The addition of RA enhanced antioxidant and anticancer activities and promoting the mineralisation process.

Casein is a micellar protein rich in glutamic and aspartic acids as well as in phosphoserine. Considering its native affinity for calcium and the connection of sub-micelles through calcium phosphate nanoclusters, this protein holds promise for stimulating biomimetic mineralisation phenomena and direct binding with the mineral phase of hard tissues. In this work we prepared new hybrids based on casein embedded in a poly(2-hydroxyethyl methacrylate)-polyethyleneglycol diacrylate (PHEMA-PEGDA) hydrogel. The resulting materials were investigated structurally by Fourier transform infrared (FT-IR). Casein modified the water affinity and the rheological properties of the hybrids. The microstructure was explored by scanning electron microscopy (SEM) and the distribution of the protein was established by combined SEM micrographs and elemental mapping considering the casein-specific elements (P, N and S) not contained by the synthetic hydrogel matrix. The effect of casein on the mineralisation potential and stability of the mineral phase was investigated by FT-IR and SEM when alternating incubation in Ca/P solutions is performed. Increasing casein content in the hybrids leads to improved mineralisation, with localised formation of nanoapatite phase on the protein areas in the richest sample in protein. This behaviour was proved microstructurally by SEM and through overlapping elemental distribution of Ca and P from the newly formed mineral and P, S and N from the protein. This study indicates that nanoapatite-casein-PHEMA-PEGDA nanocomposites may be developed for potential use in bone repair and regeneration.

The ever-growing field of materials with applications in the biomedical field holds great promise regarding the design and fabrication of devices with specific characteristics, especially scaffolds with personalized geometry and architecture. The continuous technological development pushes the limits of innovation in obtaining adequate scaffolds and establishing their characteristics and performance. To this end, computed tomography (CT) proved to be a reliable, nondestructive, high-performance machine, enabling visualization and structure analysis at submicronic resolutions. CT allows both qualitative and quantitative data of the 3D model, offering an overall image of its specific architectural features and reliable numerical data for rigorous analyses. The precise engineering of scaffolds consists in the fabrication of objects with well-defined morphometric parameters (e.g., shape, porosity, wall thickness) and in their performance validation through thorough control over their behavior (in situ visualization, degradation, new tissue formation, wear, etc.). This review is focused on the use of CT in biomaterial science with the aim of qualitatively and quantitatively assessing the scaffolds’ features and monitoring their behavior following in vivo or in vitro experiments. Furthermore, the paper presents the benefits and limitations regarding the employment of this technique when engineering materials with applications in the biomedical field.

Fabrication of three-dimensional (3D) scaffolds using natural biomaterials introduces valuable opportunities in bone tissue reconstruction and regeneration. The current study aimed at the development of paste-like 3D printing inks with an extracellular matrix-inspired formulation based on marine materials: sodium alginate (SA), cuttlebone (CB), and fish gelatin (FG). Macroporous scaffolds with microporous biocomposite filaments were obtained by 3D printing combined with post-printing crosslinking. CB fragments were used for their potential to stimulate biomineralization. Alginate enhanced CB embedding within the polymer matrix as confirmed by scanning electron microscopy (ESEM) and micro-computer tomography (micro-CT) and improved the deformation under controlled compression as revealed by micro-CT. SA addition resulted in a modulation of the bulk and surface mechanical behavior, and lead to more elongated cell morphology as imaged by confocal microscopy and ESEM after the adhesion of MC3T3-E1 preosteoblasts at 48 h. Formation of a new mineral phase was detected on the scaffold’s surface after cell cultures. All the results were correlated with the scaffolds’ compositions. Overall, the study reveals the potential of the marine materials-containing inks to deliver 3D scaffolds with potential for bone regeneration applications.

Mucin is a glycoprotein with proven potential in the biomaterials field, but its use is still underexploited for such applications. The present work aims to produce a synthesis of methacryloyl mucin single-network (SN) hydrogels and their double-cross-linked-network (DCN) counterparts. Following the synthesis of the mucin methacryloyl derivative, various SN hydrogels are prepared through the photopolymerization of methacrylate bonds, using reaction media with different pH values. The SN hydrogels are converted into DCN systems via supplementary cross-linking in tannic acid aqueous solution. The chemical modification of mucin is described, and the obtained product is characterized, the structural modification of mucin is assessed through FTIR spectroscopy, and the circular dichroism and the isoelectric point of methacryloyl mucin is evaluated. The affinity for aqueous media of both SN and DCN hydrogels is estimated, and the mechanical properties of the systems are assessed, both at macroscale through uniaxial compression and rheology tests and also at microscale through nanoindentation tests.

Niemann-Pick type C (NPC) disease is a rare and fatal lysosomal storage disorder presenting severe neurovisceral symptoms. Disease-causing mutations in genes encoding either NPC1 or NPC2 protein provoke accumulation of cholesterol and other lipids in specific structures of the endosomal-lysosomal system and degeneration of specific cells, notably neurons in the central nervous system (CNS). 2-hydroxypropyl-beta-cyclodextrin (CD) emerged as potential therapeutic approach based on animal studies and clinical data, but the mechanism of action on neurons has remained unclear. To address this topic in vivo, we took advantage of the retina as highly accessible part of the (CNS) and intravitreal injections as mode of drug administration. We find that CD enters the endosomal-lysosomal system of neurons and enables the release of lipid-laden lamellar inclusions, which are then removed from the extracellular space by specific types of glial cells. Thus, CD triggers a concerted action of neurons and glial cells to restore lipid homeostasis in the central nervous system.

The bioactivity of scaffolds represents a key property to facilitate the bone repair after orthopedic trauma. This study reports the development of biomimetic paste-type inks based on wollastonite (CS) and fish gelatin (FG) in a mass ratio similar to natural bone, as an appealing strategy to promote the mineralization during scaffold incubation in simulated body fluid (SBF). High-resolution 3D scaffolds were fabricated through 3D printing, and the homogeneous distribution of CS in the protein matrix was revealed by scanning electron microscopy/energy-dispersive X-ray diffraction analysis (SEM/EDX) micrographs. The bioactivity of the scaffold was suggested by an outstanding mineralization capacity revealed by the apatite layers deposited on the scaffold surface after immersion in SBF. The biocompatibility was demonstrated by cell proliferation established by MTT assay and fluorescence microscopy images and confirmed by SEM micrographs illustrating cell spreading. This work highlights the potential of the bicomponent inks to fabricate 3D bioactive scaffolds and predicts the osteogenic properties for bone regeneration applications.

The current work focuses on the development of mineral scaffolds with complex composition and controlled morphology by using a polymeric template in the form of nonwoven fibre webs fabricated through electrospinning. By a cross-linking process, gelatine fibres stable in aqueous solutions were achieved, these being further subjected to a loading step with two types of mineral phases: calcium phosphates deposited by chemical reaction and barium titanate nanoparticles as decoration on the previously achieved structures. Thus, hybrid materials were obtained and subsequently processed in terms of freeze-drying and heat treating with the purpose of burning the template and consolidating the mineral part as potential bone implants with improved biological response by external stimulation. The results confirmed the tunable morphology, as well as the considerable applicability of both as-prepared and final samples for the development of medical devices, which encourages the continuation of research in the direction of assessing the synergistic contribution of barium titanate domains polarisation/magnetisation by external applied fields.

Many tubular tissues such as blood vessels and trachea can suffer long-segmental defects through trauma and disease. With current limitations in the use of autologous grafts, the need for a synthetic substitute is of continuous interest as possible alternatives. Fabrication of these tubular organs is commonly done with techniques such as electrospinning and melt electrowriting using a rotational collector. Current additive manufacturing (AM) systems do not commonly implement the use of a rotational axis, which limits their application for the fabrication of tubular scaffolds. In this study, a four axis extrusion-based AM system similar to fused deposition modeling (FDM) has been developed to create tubular hollow scaffolds. A rectangular and a diamond pore design were further investigated for mechanical characterization, as a standard and a biomimicry pore geometry respectively. We demonstrated that in the radial compression mode the diamond pore design had a higher Young's modulus (19,8 ± 0,7 MPa compared to 2,8 ± 0,5 MPa), while in the longitudinal tensile mode the rectangular pore design had a higher Young's modulus (5,8 ± 0,2 MPa compared to 0,1 ± 0,01 MPa). Three-point bending analyses revealed that the diamond pore design is more resistant to luminal collapse compared to the rectangular design. This data showed that by changing the scaffold pore design, a wide range of mechanical properties could be obtained. Furthermore, a full control over scaffold design and geometry can be achieved with the developed 4-axis extrusion-based system, which has not been reported with other techniques. This flexibility allow the manufacturing of scaffolds for diverse tubular tissue regeneration applications by designing suitable deposition patterns to match their mechanical pre-requisites.

In this work, for the first time, a material derived from food industry waste – whey protein isolate – and a material commonly used in bone regeneration – bioactive glasses – were combined to obtain novel composite biomaterials with potential applications in bone tissue engineering (BTE). Additionally, to obtain pro-angiogenic properties, sol–gel-derived BGs doped with Cu2+ and Co2+ ions were used. Using a simple gas foaming method, ready-to-use (sterile), bioactive scaffolds with high porosity (above 70%), fully connected pore networks, and pore size suitable for BTE applications (80–350 μm) were obtained. Furthermore, scaffolds showed additional functionalities – calcium phosphate-forming ability and gradual release of therapeutic ions. Porous WPI/BG composites showed great potential for use as novel bone substitutes.

Electrospun (ESP) scaffolds are a promising type of tissue engineering constructs for large defects with limited depth. To form new functional tissue, the scaffolds need to be infiltrated with cells, which will deposit extracellular matrix. However, due to dense fiber packing and small pores, cell and tissue infiltration of ESP scaffolds is limited. Here, we combine two established methods, increasing fiber diameter and co-spinning sacrificial fibers, to create a porous ESP scaffold that allows robust tissue infiltration. Full cell infiltration across 2 mm thick scaffolds is seen 3 weeks after subcutaneous implantation in rats. After 6 weeks, the ESP scaffolds are almost fully filled with de novo tissue. Cell infiltration and tissue formation in vivo in this thickness has not been previously achieved. In addition, we propose a novel method for in vitro cell seeding to improve cell infiltration and a model to study 3D migration through a fibrous mesh. This easy approach to facilitate cell infiltration further improves previous efforts and could greatly aid tissue engineering approaches utilizing ESP scaffolds.Statement of significanceElectrospinning creates highly porous scaffolds with nano- to micrometer sized fibers and are a promising candidate for a variety of tissue engineering applications. However, smaller fibers also create small pores which are difficult for cells to penetrate, restricting cells to the top layers of the scaffolds. Here, we have improved the cell infiltration by optimizing fiber diameter and by co-spinning a sacrificial polymer. We developed novel culture technique that can be used to improve cell seeding and to study cytokine driven 3D migration through fibrous meshes. After subcutaneous implantation, infiltration of tissue and cells was observed up to throughout up to 2 mm thick scaffolds. This depth of infiltration in vivo had not yet been reported for electrospun scaffolds. The scaffolds we present here can be used for in vitro studies of migration, and for tissue engineering in defects with a large surface area and limited depth.

This study deals with the design and comprehensive evaluation of novel hydrogels based on whey protein isolate (WPI) for tissue regeneration. So far, WPI has been considered mainly as a food industry by-product and there are very few reports on the application of WPI in tissue engineering (TE). In this work, WPI-based hydrogels were modified with bioactive glass (BG), which is commonly used as a bone substitute material. Ready-to-use, sterile hydrogels were produced by a simple technique, namely heat-induced gelation. Two different concentrations (10 and 20% w/w) of sol–gel-derived BG particles of two different sizes (2.5 and

Luffa cylindrica fibers were purified through alkaline treatment and loaded with phosphate as mineral precursor. Their capacity of acting as bioactivator for an inert polymer was evaluated. In this respect, the PO43- - Luffa fibers were loaded in a polymeric matrix known not to promote biomineralization through immersion in mineralization media. The synthesized materials were subjected to alternative Ca/P baths and the formation of mineral was investigated through SEM. Also, the mechanical properties and the water affinity of the un-mineralized and mineralized materials were investigated.

The Gold standard in parietal wall hernias is represented by mesh implantation. Both wall repair and hernia-associated complications are related to the anatomic location and biomechanics of the structures involved specificity. This work reports the results of the intraoperative and postoperative evaluation of synthetic polypropylene mesh integration. The mesh and the surrounding tissue, previously removed and preserved, have been analyzed macroscopically and at microscopic level. The tissue invaded the pores of the mesh and coated the monofilaments. The right balance between the mesh type and tissular response is hard to evaluate preoperatively, due to individual variations, but we can upgrade the criteria used to personalize the treatment for the best possible outcome.

International audience; Non-biodegradable porous polystyrene (PS) scaffolds, composed of microfibers, have been prepared by electrospinning for the reconstruction of large bone defects. PS microfibers were prepared by incorporating β-TCP grains inside the polymer or grafting gold nanoparticles surface functionalized with mercaptosuccinic acid. Cytocompatibility of the three types of scaffolds (PS, β-TCP-PS and Au-PS) was studied by seeding human mesenchymal stem cells. Biocompatibility was evaluated by implanting β-TCP-PS and Au-PS scaffolds into a critical size (4mm) calvarial defect in mice. Calvaria were taken 6, 9, and 12 weeks after implantation; newly formed bone and cellular response was analyzed by microcomputed tomography (microCT) and histology. β-TCP-PS scaffolds showed a significantly higher cell proliferation in vitro than on PS or Au-PS alone; clearly, the presence of β-TCP grains improved cytocompatibility. Biocompatibility study in the mouse calvaria model showed that β-TCP-PS scaffolds were significantly associated with more newly-formed bone than Au-PS. Bone developed by osteoconduction from the defect margins to the center. A dense fibrous connective tissue containing blood vessels was identified histologically in both types of scaffolds. There was no inflammatory foci nor giant cell in these areas. AuNPs aggregates were identified histologically in the fibrosis and also incorporated in the newly-formed bone matrix. Although the different types of PS microfibers appeared cytocompatible during the in vitro experiment, they appeared biotolerated in vivo since they induced a fibrotic reaction associated with newly formed bone.

Due to the reduced ability of most harmed tissues to self-regenerate, new strategies are being developed in order to promote self-repair assisted or not by biomaterials, among these tissue engineering (TE). Human adipose-derived mesenchymal stem cells (hASCs) currently represent a promising tool for tissue reconstruction, due to their low immunogenicity, high differentiation potential to multiple cell types and easy harvesting. Gelatin is a natural biocompatible polymer used for regenerative applications, while nanodiamond particles (NDs) are used as reinforcing nanomaterial that might modulate cell behavior, namely cell adhesion, viability, and proliferation. The development of electrospun microfibers loaded with NDs is expected to allow nanomechanical sensing due to local modifications of both nanostructure and stiffness. Two aqueous suspensions with 0.5 and 1% w/v NDs in gelatin from cold water fish skin (FG) were used to generate electrospun meshes. Advanced morpho- and micro-structural characterization revealed homogeneous microfibers. Nanoindentation tests confirmed the reinforcing effect of NDs. Biocompatibility assays showed an increased viability and proliferation profile of hASCs in contact with FG_NDs, correlated with very low cytotoxic effects of the materials. Moreover, hASCs developed an elongated cytoskeleton, suggesting that NDs addition to FG materials encouraged cell adhesion. This study showed the FG_NDs fibrous scaffolds potential for advanced TE applications.

The assessment of several ink formulations for 3D printing based on two natural macromolecular compounds is presented. In the current research we have exploited the fast crosslinking potential of pectin and the remarkable shear-thinning properties of carboxylated cellulose nanofibrils, which is known to induce a desired viscoelastic behavior. Prior to 3D printing, the viscoelastic properties of the polysaccharide inks were evaluated by rheological measurements and injectability tests. The reliance of the printing parameters on the ink composition was established through one-dimensional lines printing, the base units of 3D-structures. The performance of the 3D-printed structures after ionic cross-linking was evaluated in terms of mechanical properties and rehydration behavior. MicroCT was also used to evaluate the morphology of the 3D-printed objects regarding the effect of pectin/nanocellulose ratio on the geometrical features of scaffolds. The proportionality between the two polymers proved to be the determining factor for the firmness and strength of the printed objects.

Shape fidelity and integrity are serious challenges in the 3D printing of hydrogel precursors, as they can influence the overall performance of 3D scaffolds. This work reports the development of superconcentrated inks based on sodium alginate and fish gelatin as an appealing strategy to satisfy such challenges and dictate the quality of the printed scaffolds, without using crosslinking strategies during 3D printing. SEM micrographs and micro-CT images indicate the homogeneous distribution of the polysaccharide in the gelatin-based matrix, suggesting its potential to act as a reinforcing additive. The high concentration of gelatin aqueous solution (50 wt%) and substantial incorporation of alginate have facilitated the highly accurate printability and influence the in vitro stability and mechanical properties of the printed scaffolds. An improvement of the stiffness is dictated by the increase of alginate concentration from 20 wt% to 25 wt%, and an increase of Young modulus with about 46% is reached, confirming the reinforcing effect of polysaccharide. This study highlights the potential of paste-type inks to provide high resolution 3D printed structures with appealing structural and dimensional stability, in vitro degradability and mechanical properties for biomedical applications.

This paper reports the electrospinning fabrication of flexible nanostructured tubular scaffolds, based on fish gelatin (FG) and nanodiamond nanoparticles (NDs), and their cytocompatibility with murine neural stem cells. The effects of both nanofiller and protein concentration on the scaffold morphology, aqueous affinity, size modification at rehydration, and degradation are assessed. Our findings indicate that nanostructuring with low amounts of NDs may modify the fiber properties, including a certain regional parallel orientation of fiber segments. NE-4C cells form dense clusters that strongly adhere to the surface of FG50-based scaffolds, while also increasing FG concentration and adding NDs favor cellular infiltration into the flexible fibrous FG70_NDs nanocomposite. This research illustrates the potential of nanostructured NDs-FG fibers as scaffolds for nerve repair and regeneration. We also emphasize the importance of further understanding the effect of the nanofiller-protein interphase on the microstructure and properties of electrospun fibers and on cell-interactivity.

Introduction: Abdominal wall surgery for parietal defects is done by implanting a type of mesh in the surrounding tissue above or beneath the fascia layer of the abdominal wall. The most common type of mesh used is polypropylene which sometimes takes a lot of time to be covered by the fibrous tissue. In an attempt to accelerate the cellular binding on the mesh and so to increase the recovery rate, we developed a protocol with plasma derived products to accelerate the mesh integration. Platelet rich fibrin (PRF) and platelet rich plasma (PRP) were evaluated in promoting the collagen synthesis and cell proliferation on the mesh surface. Material and Methods: We evaluated 32 patients with different types of abdominal wall defects which required polypropylene mesh implants in open surgery with the mesh implanted above the aponeurosis layer. We divided the patients into 3 groups: standard procedure, mesh augmented with PRF only, mesh augmented with PRP only. Results: Even though the number of patients involved in the study has a very small impact for a statistical analysis, the pattern observed in our prospective study reveals from the beginning that augmenting the standard procedure with plasma derived products improve the outcome (mesh integration) up to 65% faster integration. Conclusion: The technique that we used to augment the standard implant is cost-effective and simple to use in the surgical theatre.

In this work we report the potential of nanostructured fibers consisting of nanodiamond particles (NDPs) and fish gelatin (FG) to modulate the mechanical properties of fish gelatin hydrogels, in the aim of developing bioinspired ECM analogues. NDPS-loaded FG fibers were obtained by electrospinning. The biocomposites were obtained through the enzymatic crosslinking of gelatin in the presence of NDPs-loaded FG fibers. The mechanical behavior was assessed at different preparative stages (precursors, fibrous mesh, biocomposite scaffolds).

Synthetic polymers have had a major impact on the biomedical field. However, all polymers have their advantages and disadvantages, so that the selection of a certain polymeric material always is a compromise with regard to many properties, such as synthetic accessibility, solubility, thermal properties, biocompatibility, and degradability. The development of novel polymers with superior properties for medical applications is the focus of many research groups. The present study highlights the use of poly(2-isopropenyl-2-oxazoline) (PiPOx), as biocompatible functional polymer to develop synthetic hydrogel materials using a simple straightforward synthesis protocol. A library of hydrogels was obtained by chemical cross-linking of PiPO(x), using eight different nontoxic and bio-based dicarboxylic acids. The equilibrium swelling degree of the final material can be modulated by simple modification of the composition of the reaction mixture, including the polymer concentration in the feed ratio between the 2-oxazoline pendent groups and the carboxylic acid groups as well as the cross-linker length. The hydrogels with the highest water uptake were selected for further investigations regarding their potential use as biomaterials. We evaluated the thermoresponsiveness, the pH degradability under physiological conditions, and demonstrated proof-of-concept drug delivery experiments. The in vitro cellular studies demonstrated the noncytotoxic character of the PiPOx hydrogels, and their protein repellent properties, while mineralization studies revealed that such scaffolds do not promote mineralization/calcification phenomena. In view of these results, these hydrogels show potential use as ophthalmologic materials or in drug delivery applications.

Polymeric materials that respond to light stimulus represent an important research area in the field of biomaterials. Light-responsive biomaterials have received significant attention due to their ability to provide spatially and temporally control and their potential to be less invasive. In this book chapter, we highlight the exciting progress realized in the biomedical field in recent years on photoresponsive polymeric systems. More precisely, we discuss the rational design of photoactive compounds, the role they have in the photoresponsive systems, the underlying principles behind photoresponsive behavior, and the subsequent applications in the biomaterial field. We also present the progress made in the field of photopharmacology, photoregulated drug delivery, and bioimaging, emphasizing the advantages on the basis of different architectures such as micelles, hydrogels, nanoparticles, and photoresponsive supramolecular assemblies. Finally, analytical techniques used to characterize the photoresponsive materials are expound.

This work describes the synthesis of composite particles for bone regeneration. The developed method is based on a bio-inspired approach starting from the composition, properties and hierarchical organization of bone extracellular matrix (ECM). The composite material was designed as spherical particles able to ensure interconnected porosity through their assembling inside the bone defect. nanohydroxyapatite was generated in the organic matrix in order to mimic the composition and the organization of the mineral phase in bone tissue. A collagen derivative was used as main natural polymer of the organic matrix of the composite material, in order to mimic the composition of bone ECM. Alginate represents the second organic polymer due to its recognized capacity to easily generate spherical particles in divalent cations solutions. The combination of this polysaccharide with the two previously mentioned components simultaneously responds the architectural and compositional constraints of this approach. The particles were obtained using a modular electrostatic bead generator developed in our laboratory. Briefly, a solution containing the biopolymers was extruded into a mineralisation solution. Spherical particles with diameters of about 500 μm were obtained. They were characterised by scanning electron microscopy, X-ray diffraction, stability in aqueous media. The obtained results confirmed the importance of alginate to generate spherical particles and the potential of such materials to successfully serve the targeted application.

This work describes the investigation of the properties of hydrogels based on methacrylamide-modified gelatin (GelMA) and polyvinylpyrrolidone (PVP) with potential applications in wound treatment. While the semi-natural polymer insures the biocompatibility and biodegradability of the synthesized materials, the synthetic polymer was selected due to its water affinity and interesting mechanical properties. The efficiency of the polymerization process and the stability of the PVP within the semi interpenetrated polymer network (semiIPN) were verified through gel fraction study. The water affinity, tensile strength and rheological properties of the hydrogels were also investigated.

This work presents the synthesis and characterization of natural-synthetic hydrogels based on gelatin (Gel) and polyvinylpyrrolidone (PVP), with potential for skin grafts applications. The natural component, Gel insures the biocompatibility and biodegradability of the bicomponent system [1], while the synthetic counterpart, PVP, is a physiologic inert component, extensively used in medicine due to its water affinity and due to its capacity of confer elasticity to films and membranes with potential applications in skin grafts [2]. The obtained hydrogels were subjected to morpho-structural analysis and rheological and mechanical tests (traction). The water affinity of the systems was estimated and their capacity to generate porous substrates through freeze-drying was evaluated.

International audience; Nano-apatite and gelatin-alginate hydrogel microparticles have been prepared by a one-step synthesis combined with electrostatic bead generation, for the reconstruction of bone defects. Based on the analysis of bone composition, architecture and embryonic intramembranous ossification, a bio-inspired fabrication has been developed. Accordingly, the mineral phase has been in situ synthesized, calcifying the hydrogel matrix while the latter was crosslinked, finally generating microparticles that can assemble into a bone defect to ensure interconnected pores. Although nano-apatite-biopolymer composites have been widely investigated, microstructural optimization to provide improved distribution and stability of the mineral is rarely achieved. The optimization of the developed method progressively resulted in two types of formulations (15P and 7.5P), with 15 and 7.5 (wt%) phosphate content in the initial precursor. The osteolytic potential was investigated using differentiated macrophages. A commercially available calcium phosphate bone graft substitute (Eurocer 400) was incorporated into the hydrogel, and the obtained composites were in vitro tested for comparison. The cytocompatibility of the microparticles was studied with mouse osteoblast-like cell line MC3T3-E1. Results indicated the best in vitro performance have been obtained for the sample loaded with 7.5P. Preliminary evaluation of biocompatibility into a critical size (3 mm) defect in rabbits showed that 7.5P nanocomposite is associated with newly formed bone in the proximity of the microparticles, after 28 days.

Casein is a phosphoprotein and accordingly, its capacity to induce formation of apatite was investigated using a biomimetic method. The protein was physically immobilized into a synthetic polymer network generating hybrid scaffolds. The obtained hydrogels contained uniformly distributed nanosized casein grains. The incubation of such materials in synthetic body fluid (SBF 1.25x) led to formation of nanosized biologic-like apatite. The resulting materials have been characterized by infrared spectrometry and scanning electron microscopy.