Induced Hydrophilicity and In Vitro Preliminary Osteoblast Response of Polyvinylidene Fluoride (PVDF) Coatings Obtained via MAPLE Deposition and Subsequent Thermal Treatment.

Recent advancements in biomedicine have focused on designing novel and stable interfaces that can drive a specific cellular response toward the requirements of medical devices or implants. Among these, in recent years, electroactive polymers (i.e., polyvinylidene fluoride or PVDF) have caught the attention within the biomedical applications sector, due to their insolubility, stability in biological media, in vitro and in vivo non-toxicity, or even piezoelectric properties. However, the main disadvantage of PVDF-based bio-interfaces is related to the absence of the functional groups on the fluoropolymer and their hydrophobic character leading to a deficiency of cell adhesion and proliferation. This work was aimed at obtaining hydrophilic functional PVDF polymer coatings by using, for the first time, the one-step, matrix-assisted pulsed evaporation (MAPLE) method, testing the need of a post-deposition thermal treatment and analyzing their preliminary capacity to support MC3T3-E1 pre-osteoblast cell survival. As osteoblast cells are known to prefer rough surfaces, MAPLE deposition parameters were studied for obtaining coatings with roughness of tens to hundreds of nm, while maintaining the chemical properties similar to those of the pristine material. The in vitro studies indicated that all surfaces supported the survival of viable osteoblasts with active metabolisms, similar to the "control" sample, with no major differences regarding the thermally treated materials; this eliminates the need to use a secondary step for obtaining hydrophilic PVDF coatings. The physical-chemical characteristics of the thin films, along with the in vitro analyses, suggest that MAPLE is an adequate technique for fabricating PVDF thin films for further bio-applications.

Drug Delivery Systems Based on Titania Nanotubes and Active Agents for Enhanced Osseointegration of Bone Implants.

TiO2 nanotubes (TNTs) are attractive nanostructures for localized drug delivery. Owing to their excellent biocompatibility and physicochemical properties, numerous functionalizations of TNTs have been attempted for their use as therapeutic agent delivery platforms. In this review, we discuss the current advances in the applications of TNT-based delivery systems with an emphasis on the various functionalizations of TNTs for enhancing osteogenesis at the bone-implant interface and for preventing implant-related infection. Innovation of therapies for enhancing osteogenesis still represents a critical challenge in regeneration of bone defects. The overall concept focuses on the use of osteoconductive materials in combination with the use of osteoinductive or osteopromotive factors. In this context, we highlight the strategies for improving the functionality of TNTs, using five classes of bioactive agents: growth factors (GFs), statins, plant derived molecules, inorganic therapeutic ions/nanoparticles (NPs) and antimicrobial compounds.

Graphene nanoplatelets-sericin surface-modified Gum alloy for improved biological response.

In this study a "Gum Metal" titanium-based alloy, Ti-31.7Nb-6.21Zr-1.4Fe-0.16O, was synthesized by melting and characterized in order to evaluate its potential for biomedical applications. The results showed that the newly developed alloy presents a very high strength, high plasticity and a low Young's modulus relative to titanium alloys currently used in medicine. For further bone implant applications, the newly synthesized alloy was surface modified with graphene nanoplatelets (GNP), sericin (SS) and graphene nanoplatelets/sericine (GNP-SS) composite films via Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The characterization of each specimen was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle (CA) measurements, and Fourier Transform Infrared Spectroscopy (FTIR). The materials' surface analyses suggested the successful coating of GNP, SS and GNP-SS onto the alloy surface. Additionally, the activities of pre-osteoblasts such as cell adhesion, cytoskeleton organization, cell proliferation and differentiation potentials exhibited on these substrates were investigated. Results showed that the GNP-SS-coated substrate significantly enhanced the growth and osteogenic differentiation of MC3T3-E1 cells when compared to bare and GNP-coated alloy. Collectively, the results show that GNP-SS surface-modified Gum alloy can modulate the bioactivity of the pre-osteoblasts holding promise for improved biological response in vivo.

Characterization and In Vitro and In Vivo Assessment of a Novel Cellulose Acetate-Coated Mg-Based Alloy for Orthopedic Applications.

Despite their good biocompatibility and adequate mechanical behavior, the main limitation of Mg alloys might be their high degradation rates in a physiological environment. In this study, a novel Mg-based alloy exhibiting an elastic modulus E = 42 GPa, Mg-1Ca-0.2Mn-0.6Zr, was synthesized and thermo-mechanically processed. In order to improve its performance as a temporary bone implant, a coating based on cellulose acetate (CA) was realized by using the dipping method. The formation of the polymer coating was demonstrated by FT-IR, XPS, SEM and corrosion behavior comparative analyses of both uncoated and CA-coated alloys. The potentiodynamic polarization test revealed that the CA coating significantly improved the corrosion resistance of the Mg alloy. Using a series of in vitro and in vivo experiments, the biocompatibility of both groups of biomaterials was assessed. In vitro experiments demonstrated that the media containing their extracts showed good cytocompatibility on MC3T3-E1 pre-osteoblasts in terms of cell adhesion and spreading, viability, proliferation and osteogenic differentiation. In vivo studies conducted in rats revealed that the intramedullary coated implant for fixation of femur fracture was more efficient in inducing bone regeneration than the uncoated one. In this manner, the present study suggests that the CA-coated Mg-based alloy holds promise for orthopedic aplications.

Attenuation of the macrophage inflammatory activity by TiO2 nanotubes via inhibition of MAPK and NF-κB pathways.

Biomaterial implantation in a living tissue triggers the activation of macrophages in inflammatory events, promoting the transcription of pro-inflammatory mediator genes. The initiation of macrophage inflammatory processes is mainly regulated by signaling proteins of mitogen-activated protein kinase (MAPK) and by nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. We have previously shown that titania nanotubes modified Ti surfaces (Ti/TiO2) mitigate the immune response, compared with flat Ti surfaces; however, little is known regarding the underlying mechanism. Therefore, the aim of this study is to investigate the mechanism(s) by which this nanotopography attenuates the inflammatory activity of macrophages. Thus, we analyzed the effects of TiO2 nanotubes on the activation of MAPK and NF-κB signaling pathways in standard and lipopolysaccharide-evoked conditions. Results showed that the Ti/TiO2 significantly reduce the expression levels of the phosphorylated forms of p38, ERK1/2, c-Jun NH2-terminal kinase (JNK), IKKß, and IkB-α. Furthermore, a significant reduction in the p65 nuclear accumulation on the nanotubular surface was remarked. Following, by using specific MAPK inhibitors, we observed that lipopolysaccharide-induced production of monocyte chemotactic protein-1 and nitric oxide was significantly inhibited on the Ti/TiO2 surface via p38 and ERK1/2, but not via JNK. However, the selective inhibitor for JNK signaling pathway (SP600125) was effective in reducing tumor necrosis factor alpha release as well as monocyte chemotactic protein-1 and nitric oxide production. Altogether, these data suggest that titania nanotubes can attenuate the macrophage inflammatory response via suppression of MAPK and NF-κB pathways providing a potential mechanism for their anti-inflammatory activity.

In vitro performance assessment of new beta Ti-Mo-Nb alloy compositions.

New ß-titanium based alloys with low Young's modulus are currently required for the next generation of metallic implant materials to ensure good mechanical compatibility with bone. Several of these are representatives of the ternary Ti-Mo-Nb system. The aim of this paper is to assess the in vitro biological performance of five new low modulus alloy compositions, namely Ti12Mo, Ti4Mo32Nb, Ti6Mo24Nb, Ti8Mo16Nb and Ti10Mo8Nb. Commercially pure titanium (cpTi) was used as a reference material. Comparative studies of cell activity exhibited by MC3T3-E1 pre-osteoblasts over short- and long-term culture periods demonstrated that these newly-developed metallic substrates exhibited an increased biocompatibility in terms of osteoblast proliferation, collagen production and extracellular matrix mineralization. Furthermore, all analyzed biomaterials elicited an almost identical cell response. Considering that macrophages play a pivotal role in bone remodeling, the behavior of a monocyte-macrophage cell line, RAW 264.7, was also investigated showing a slightly lower inflammatory response to Ti-Mo-Nb biomaterials as compared with cpTi. Thus, the biological performances together with the superior mechanical properties recommend these alloys for bone implant applications.

Reduced inflammatory activity of RAW 264.7 macrophages on titania nanotube modified Ti surface.

Macrophages play a pivotal role in the hosts response to biomaterials being considered as an essential cell type during both optimal tissue-implant integration and pathologic process of implant failure. Hence, understanding of their cellular activity on biomaterials is important for improving evaluation and design of biomaterials for biomedical applications. In the present study, we have comparatively investigated the interactions of titania nanotubes (78 nm diameter) and commercial pure Ti with RAW 264.7 macrophages in both standard and pro-inflammatory (stimulation with lipopolysaccharide, LPS) culture conditions. In vitro tests showed that TiO2 nanotubes exhibited significantly decreased inflammatory activity of macrophages with respect to cytokine and chemokine gene expression/protein secretion, induction of foreign body giant cells (FBGCs) and nitric oxide (NO) release thereby mitigating the inflammatory response induced by LPS as compared to flat Ti surface. Therefore, our results suggest a novel role of TiO2 nanotubes in modulating macrophage response in biomaterial-associated bacterial infections. Overall, the current study provides new insight into how TiO2 nanotubes can be involved in macrophage activation and supports the great promise of such surface modifications for biomedical applications.