Advanced Binary Guanosine and Guanosine 5'-Monophosphate Cell-Laden Hydrogels for Soft Tissue Reconstruction by 3D Bioprinting.

Soft tissue defects or pathologies frequently necessitate the use of biomaterials that provide the volume required for subsequent vascularization and tissue formation as autrografts are not always a feasible alternative. Supramolecular hydrogels represent promising candidates because of their 3D structure, which resembles the native extracellular matrix, and their capacity to entrap and sustain living cells. Guanosine-based hydrogels have emerged as prime candidates in recent years since the nucleoside self-assembles into well-ordered structures like G-quadruplexes by coordinating K+ ions and π-π stacking, ultimately forming an extensive nanofibrillar network. However, such compositions were frequently inappropriate for 3D printing due to material spreading and low shape stability over time. Thus, the present work aimed to develop a binary cell-laden hydrogel capable of ensuring cell survival while providing enough stability to ensure scaffold biointegration during soft tissue reconstruction. For that purpose, a binary hydrogel made of guanosine and guanosine 5'-monophosphate was optimized, rat mesenchymal stem cells were entrapped, and the composition was bioprinted. To further increase stability, the printed structure was coated with hyperbranched polyethylenimine. Scanning electron microscopic studies demonstrated an extensive nanofibrillar network, indicating excellent G-quadruplex formation, and rheological analysis confirmed good printing and thixotropic qualities. Additionally, diffusion tests using fluorescein isothiocyanate labeled-dextran (70, 500, and 2000 kDa) showed that nutrients of various molecular weights may diffuse through the hydrogel scaffold. Finally, cells were evenly distributed throughout the printed scaffold, cell survival was 85% after 21 days, and lipid droplet formation was observed after 7 days under adipogenic conditions, indicating successful differentiation and proper cell functioning. To conclude, such hydrogels may enable the 3D bioprinting of customized scaffolds perfectly matching the respective soft tissue defect, thereby potentially improving the outcome of the tissue reconstruction intervention.

Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival.

Tissue defects can lead to serious health problems and often require grafts or transplants to repair damaged soft tissues. However, these procedures can be complex and may not always be feasible due to a lack of available tissue. Hydrogels have shown potential as a replacement for tissue grafts due to their ability to support cell survival and encapsulate biomolecules such as growth factors. In particular, guanosine-based hydrogels have been explored as a potential solution, but they often exhibit limited stability which hampers their use in the biofabrication of complex grafts. To address this issue, we explored the use of borate ester chemistry and more complex boric acid derivatives to improve the stability and properties of guanosine-based hydrogels. We hypothesized that the aromatic rings in these derivatives would enhance the stability and printability of the hydrogels through added π-π stack interactions. After optimization, 13 compositions containing either 2-naphthylboronic acid or boric acid were selected. Morphology studies shows a well-defined nanofibrilar structure with good printable properties (thixotropic behaviour, print fidelity and printability). Moreover, the pH of all tested hydrogels was within the range suitable for cell viability (7.4-8.3). Nevertheless, only the boric acid-based formulations were stable for at least 7 days. Thus, our results clearly demonstrated that the presence of additional aromatic rings did actually impair the hydrogel properties. We speculate that this is due to steric hindrance caused by adjacent groups, which disrupt the correct orientation of the aromatic groups required for effective π-π stack interactions of the guanosine building block. Despite this drawback, the developed guanosine-boric acid hydrogel exhibited good thixotropic properties and was able to support cell survival, proliferation, and migration. For instance, SaOS-2 cells planted on these printed structures readily migrated into the hydrogel and showed nearly 100% cell viability after 7 days. In conclusion, our findings highlight the potential of guanosine-boric acid hydrogels as tissue engineering scaffolds that can be readily enhanced with living cells and bioactive molecules. Thus, our work represents a significant advancement towards the development of functionalized guanosine-based hydrogels.

Nucleoside-Based Supramolecular Hydrogels: From Synthesis and Structural Properties to Biomedical and Tissue Engineering Applications.

Supramolecular hydrogels are of great interest in tissue scaffolding, diagnostics, and drug delivery due to their biocompatibility and stimuli-responsive properties. In particular, nucleosides are promising candidates as building blocks due to their manifold noncovalent interactions and ease of chemical modification. Significant progress in the field has been made over recent years to allow the use of nucleoside-based supramolecular hydrogels in the biomedical field, namely drug delivery and 3D bioprinting. For example, their long-term stability, printability, functionality, and bioactivity have been greatly improved by employing more than one gelator, incorporating different cations, including silver for antibacterial activity, or using additives such as boric acid or even biomolecules. This now permits their use as bioinks for 3D printing to produce cell-laden scaffolds with specified geometries and pore sizes as well as a homogeneous distribution of living cells and bioactive molecules. We have summarized the latest advances in nucleoside-based supramolecular hydrogels. Additionally, we discuss their synthesis, structural properties, and potential applications in tissue engineering and provide an outlook and future perspective on ongoing developments in the field.

Bacteriostatic Poly Ethylene Glycol Plasma Coatings for Orthodontic Titanium Mini-Implants.

Titanium mini-implants are used as anchorage for orthodontic tooth movements. However, these implants present problems due to the infection of surrounding tissues. The aim of this work was to obtain a polyethylene glycol (PEG) layer by plasma in order to achieve a bacteriostatic surface. Titanium surfaces were activated by argon plasma and, after, by PEG plasma with different powers (100, 150 and 200 W) for 30 and 60 min. The roughness was determined by white light interferometer microscopy and the wettability was determined by the contact angle technique. Surface chemical compositions were characterized by X-ray photoelectron spectroscopy (XPS) and cytocompatibility and cell adhesion studies were performed with fibroblast (hFFs) and osteoblast (SAOS-2) cells. Bacterial cultures with Spectrococcus Sanguinis and Lactobacillus Salivarius were performed, and bacterial colonization was determined. The results showed that plasma treatments do not affect the roughness. Plasma makes the surfaces more hydrophilic by decreasing the contact angles from 64.2° for titanium to 5.2° for argon-activated titanium, with values ranging from 12° to 25° for the different PEG treatments. The plasma has two effects: the cleaning of the surface and the formation of the PEG layer. The biocompatibility results were, for all cases, higher than 80%. The polymerization treatment with PEG reduced the adhesion of hFFs from 7000 to 6000 and, for SAOS-2, from 14,000 to 6500, for pure titanium and those treated with PEG, respectively. Bacterial adhesion was also reduced from 600 to 300 CFU/mm2 for Spetrococcuns Sanguinis and from 10,000 to 900 CFU/mm2 for Lactobacillus Salivarius. The best bacteriostatic treatment corresponded to PEG at 100 W and 30 s. As a consequence, the PEG coating would significantly prevent the formation of bacterial biofilm on the surface of titanium mini-implants.

Evaluation of the inflammatory and osteogenic response induced by titanium particles released during implantoplasty of dental implants.

Implantoplasty is a mechanical decontamination technique that consists of removing the threads and polishing and smoothing the dental implant surface. During implantoplasty there is a large release of titanium metal particles that might provoke a proinflammatory response and reduce the viability of osteogenic cells. We analyze the inflammatory and osteogenic response induced by Ti6Al4V particles released during implantoplasty and by as-received commercially pure Ti particles. Macrophages stimulated with metal particles obtained by implantoplasty and with as-received Ti particles showed an increased proinflammatory expression of TNF-α and a decreased expression of TGF-ß and CD206. Regarding cytokine release, there was an increase in IL-1ß, while IL-10 decreased. The osteogenic response of Ti6Al4V extracts showed a significant decrease in Runx2 and OC expression compared to the controls and commercially pure Ti extracts. There were no relevant changes in ALP activity. Thus, implantoplasty releases metal particles that seems to induce a pro-inflammatory response and reduce the expression of osteogenic markers.

Antibacterial approaches in tissue engineering using metal ions and nanoparticles: From mechanisms to applications.

Bacterial infection of implanted scaffolds may have fatal consequences and, in combination with the emergence of multidrug bacterial resistance, the development of advanced antibacterial biomaterials and constructs is of great interest. Since decades ago, metals and their ions had been used to minimize bacterial infection risk and, more recently, metal-based nanomaterials, with improved antimicrobial properties, have been advocated as a novel and tunable alternative. A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria. Antibacterial mechanisms such as oxidative stress induction, ion release and disruption of biomolecules are currently well accepted. However, the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood. The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing, and allow to mitigate potential side effects to the host. Starting with a general overview of antibacterial mechanisms, we subsequently focus on specific metal ions such as silver, zinc, copper, iron and gold, and outline their distinct modes of action. Finally, we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure.

Direct extrusion of individually encapsulated endothelial and smooth muscle cells mimicking blood vessel structures and vascular native cell alignment.

Cardiovascular diseases (CVDs) are considered the principal cause of worldwide death, being atherosclerosis the main etiology. Up to now, the predominant treatment for CVDs has been bypass surgery from autologous source. However, due to previous harvest or the type of disease, this is not always an option. For this reason, tissue engineered blood vessels (TEBV) emerged as an alternative graft source for blood vessel replacement. In order to develop a TEBV, it should mimic the architecture of a native blood vessel encapsulating the specific vascular cells in their respective layers with native alignment, and with appropriate mechanical stability. Here, we propose the extrusion of two different cell encapsulating hydrogels, mainly alginate and collagen, and a sacrificial polymer, through a triple coaxial nozzle, which in contact with a crosslinking solution allows the formation of bilayered hollow fibers, mimicking the architecture of native blood vessels. Prior to extrusion, the innermost cell encapsulating hydrogel was loaded with human umbilical vein endothelial cells (HUVECs), whereas the outer hydrogel was loaded with human aortic smooth muscle cells (HASMCs). The size of the TEVB could be controlled by changing the injection speed, presenting homogeneity between the constructs. The obtained structures were robust, allowing its manipulation as well as the perfusion of liquids. Both cell types presented high rates of survival after the extrusion process as well as after 20 d in culture (over 90%). Additionally, a high percentage of HASMC and HUVEC were aligned perpendicular and parallel to the TEBV, respectively, in their own layers, resembling the physiological arrangement foundin vivo. Our approach enables the rapid formation of TEBV-like structures presenting high cell viability and allowing proliferation and natural alignment of vascular cells.

Torsion Resistance of the Ball Head System Screw and Screwdriver for Angled Screw Channels on Implant Prosthetics.

The primary objective of this study was to determine the torsion resistance of the Ball Head System (BHS) screw and screwdriver set at 0°, 20°, and 30° angulations. The secondary objective was to compare the BHS set with the 1.3-mm hexagonal screwdriver system (HexS) at 20° and analyze the condition of the BHS after 10 and 30 iterations with 30 N·cm torque at 30° angulation. A workbench made from type 4 plaster with 6 steel implant replicas (external hexagon, 4.1 mm) inserted at 0°, 20°, and 30° angulation was designed. An analogical torque meter was used. The deformations produced on the whole set were examined by field emission scanning electron microscopy. A descriptive analysis was performed. The maximum torque performance for BHS at 30° angulation was 54 ± 12 N·cm. Most screws could be removed despite the deformations produced. At 20° angulation, the BHS set achieved an average torque resistance of 67 ± 12 N·cm, whereas the HexS failed at 45 ± 2 N·cm. Although the iterations performed at 30 N·cm torque and 20° angulation produced some deformations on BHS sets; these could be tightened and unscrewed. The BHS allows tightening at a torque of up to 54 N·cm. Under the same conditions, BHS showed more torque resistance than HexS. Deformation of BHS sets was directly related to the number of iterations.

Comparison between Sandblasted Acid-Etched and Oxidized Titanium Dental Implants: In Vivo Study.

The surface modifications of titanium dental implants play important roles in the enhancement of osseointegration. The objective of the present study was to test two different implant surface treatments on a rabbit model to investigate the osseointegration. The tested surfaces were: a) acid-etched surface with sandblasting treatment (SA) and b) an oxidized implant surface (OS). The roughness was measured by an interferometeric microscope with white light and the residual stress of the surfaces was measured with X-ray residual stress Bragg-Bentano diffraction. Six New Zealand white rabbits were used for the in vivo study. Implants with the two different surfaces (SA and OS) were inserted in the femoral bone. After 12 weeks of implantation, histological and histomorphometric analyses of the blocks containing the implants and the surrounding bone were performed. All the implants were correctly implanted and no signs of infection were observed. SA and OS surfaces were both surrounded by newly formed trabeculae. Histomorphometric analysis revealed that the bone-implant contact % (BIC) was higher around the SA implants (53.49 ± 8.46) than around the OS implants (50.94 ± 16.42), although there were no significant statistical differences among them. Both implant surfaces (SA and OS) demonstrated a good bone response with significant amounts of newly formed bone along the implant surface after 12 weeks of implantation. These results confirmed the importance of the topography and physico-chemical properties of dental implants in the osseointegration.

Enhanced osteoconductivity on electrically charged titanium implants treated by physicochemical surface modifications methods.

Biomimetic design is a key tenet of orthopedic device technology, and in particular the development of responsive surfaces that promote ion exchange with interfacing tissues, facilitating the ionic events that occur naturally during bone repair, hold promise in orthopedic fixation strategies. Non-bioactive nanostructured titanium implants treated by shot-blasting and acid-etching (AE) induced higher bone implant contact (BIC=52% and 65%) compared to shot-blasted treated (SB) implants (BIC=46% and 47%) at weeks 4 and 8, respectively. However, bioactive charged implants produced by plasma (PL) or thermochemical (BIO) processes exhibited enhanced osteoconductivity through specific ionic surface-tissue exchange (PL, BIC= 69% and 77% and BIO, BIC= 85% and 87% at weeks 4 and 8 respectively). Furthermore, bioactive surfaces (PL and BIO) showed functional mechanical stability (resonance frequency analyses) as early as 4 weeks post implantation via increased total bone area (BAT=56% and 59%) ingrowth compared to SB (BAT=35%) and AE (BAT=35%) surfaces.

In vitro evaluation of a multispecies oral biofilm over antibacterial coated titanium surfaces.

Peri-implantitis is an infectious disease that affects the supporting soft and hard tissues around dental implants and its prevalence is increasing considerably. The development of antibacterial strategies, such as titanium antibacterial-coated surfaces, may be a promising strategy to prevent the onset and progression of peri-implantitis. The aim of this study was to quantify the biofilm adhesion and bacterial cell viability over titanium disc with or without antibacterial surface treatment. Five bacterial strains were used to develop a multispecies oral biofilm. The selected species represent initial (Streptococcus oralis and Actinomyces viscosus), early (Veillonella parvula), secondary (Fusobacterium nucleatum) and late (Porphyromonas gingivalis) colonizers. Bacteria were sequentially inoculated over seven different types of titanium surfaces, combining different roughness level and antibacterial coatings: silver nanoparticles and TESPSA silanization. Biofilm formation, cellular viability and bacterial quantification over each surface were analyzed using scanning electron microscopy, confocal microscopy and real time PCR. Biofilm formation over titanium surfaces with different bacterial morphologies could be observed. TESPSA was able to significantly reduce the cellular viability when compared to all the surfaces (p < 0.05). Silver deposition on titanium surface did not show improved results in terms of biofilm adhesion and cellular viability when compared to its corresponding non-coated surface. The total amount of bacterial biofilm did not significantly differ between groups (p > 0.05). TESPSA was able to reduce biofilm adhesion and cellular viability. However, silver deposition on titanium surface seemed not to confer these antibacterial properties.

Novel Ball Head Screw and Screwdriver Design for Implant-Supported Prostheses With Angled Channels: A Finite Element Analysis.

The primary objective of this study was to design the optimal geometry of a novel screwdriver, create the grooves on a ball head screw, and demonstrate its resistance to a torque of up to 40 Ncm at angulations of 0°, 15°, and 30° by using nonlinear finite element analysis. A secondary objective was to create a foolproof, easily recognizable system. The grooved ball head screw and geometry of the screwdriver, functioning from an angulation of 0° to 30°, was generated using Pro-ENGINEER Wildfire 5.0 software. Static structural analyses among bodies in contact were performed at different angles of 0°, 15°, and 30° at a torque of 20 Ncm and 40 Ncm using nonlinear finite element simulation by means of ANSYS 12.0. The maximum stress supported by the ball head screw and screwdriver was similar at 20 Ncm and 40 Ncm. Although greater deformations were found at 40 Ncm, these were small and might not affect the performance of the system. Further, the rupture torque value for the M2 connection was 55 Ncm for 0° and 30°, and 47.5 Ncm for 15°. Numerical simulation showed that the ball head system design can achieve the mechanical strength requirements expected for screws used in implant-supported restorations at an angulation of up to 30°. Finite element analysis showed this novel ball head screw and screwdriver system to be a good solution for angled screw channels in implant-supported prostheses.

Regenerating Bone via Multifunctional Coatings: The Blending of Cell Integration and Bacterial Inhibition Properties on the Surface of Biomaterials.

In dentistry and orthopedics, it is well accepted that implant fixation is a major goal. However, an emerging concern is bacterial infection. Infection of metallic implants can be catastrophic and significantly reduce patient quality of life. Accordingly, in this work, we focus on multifunctional coatings to simultaneously address and mitigate both these problems. We have developed a tailor-made peptide-based chemical platform that integrates the well-known RGD cell adhesive sequence and the lactoferrin-derived LF1-11 antimicrobial peptide. The platform was covalently grafted on titanium via silanization and the functionalization process characterized by contact angle, XPS, and QCM-D. The presence of the platform statistically improved the adhesion, proliferation and mineralization of osteoblast-like cells compared to control surfaces. At the same time, colonization by representative bacterial strains was significantly reduced on the surfaces. Furthermore, the biological potency of the multifunctional platform was verified in a co-culture in vitro model. Our findings demonstrate that this multifunctional approach can be useful to functionalize biomaterials to both improve cell integration and reduce the risk of bacterial infection.

Biofunctional polyethylene glycol coatings on titanium: An in vitro-based comparison of functionalization methods.

Three methods for the production of Polyethylene glycol (PEG) coatings on titanium are compared, i.e. plasma polymerization, electrodeposition and silanization. The compared deposition methods presented similar wettability (hydrophilic coatings), chemical composition assessed by XPS and thickness around 1nm. The coatings lowered albumin adsorption and presented a decreased fibroblast, Streptococcus sanguinis and Lactobacillus salivarius adhesion. Immobilization of a cell adhesion peptide (RGD) presented a higher fibroblast adhesion and no alteration of the bacterial adhesion, giving three methods for the biofunctionalization of titanium for dental implants. The feasibility of each methodology is compared in terms of the process parameters in order to provide a guide for the election of the methodology.

Surface immobilization and bioactivity of TGF-ß1 inhibitor peptides for bone implant applications.

TGF-ß1 is the most related cytokine with the production of fibrotic tissue. It plays an important role on the production of collagen by fibroblasts and other types of cells. The inhibition of this cytokine reduces fibrosis in various types of tissue. Biofunctionalization of dental and orthopedic implants with biomolecules enables modification of the physical, chemical and biochemical properties of their surfaces to improve its biological and clinical performance. Our objective was to develop a reliable method to immobilize oligopeptides on Ti surfaces to obtain a surface with TGF-ß1 inhibitory activity that will potentially minimize fibrotic encapsulation of implants during the process of osseointegration. We covalently immobilized TGF-ß1 inhibitor P17-peptides on Ti surfaces and assessed by characterizing each step of the process that we successfully biofunctionalized the implant surfaces. High amounts of peptides were anchored and homogeneously distributed on the surfaces with mechanical and thermochemical stability after in vitro simulated challenges. Notably, the immobilized peptides retained their TGF-ß1 inhibitory activity in vitro. Thus, these biofunctional coatings are potential candidates for inducing a fast and reliable osseointegration in vivo.

Determination of fluid leakages in the different screw-retained implant-abutment connections in a mechanical artificial mouth.

This study shows the potential risk of microfiltration between two different types of implant-abutment connections screwed at 45 Ncm: external and internal. For the first time the use of a mechanical artificial mouth is used with the values (compression and torsion loads with a frequency of 2 Hz) of the human chewing. The mechanical tests were performed with an artificial saliva at 37°C. The microgap in the connection was measured by an Image Analysis software incorporated in a high resolution scanning electron microscopy. Implant connections were filled with methylene blue by using self-adjustable precision pipettes and the quantity of leakage was determined by high sensitivity spectometry. We showed that the internal connection has lower microgaps compared to the external ones and these microgaps increased with the number of mechanical cycles. The leakage of methylene blue was higher when the external connection was performed. Microgaps and the influence of the mechanical loads are very important for the long-term behavior avoiding the bacteria colonization in the dental implants. These aspects should be known by the implantologists.

Biofunctionalization strategies on tantalum-based materials for osseointegrative applications.

The use of tantalum as biomaterial for orthopedic applications is gaining considerable attention in the clinical practice because it presents an excellent chemical stability, body fluid resistance, biocompatibility, and it is more osteoconductive than titanium or cobalt-chromium alloys. Nonetheless, metallic biomaterials are commonly bioinert and may not provide fast and long-lasting interactions with surrounding tissues. The use of short cell adhesive peptides derived from the extracellular matrix has shown to improve cell adhesion and accelerate the implant's biointegration in vivo. However, this strategy has been rarely applied to tantalum materials. In this work, we have studied two immobilization strategies (physical adsorption and covalent binding via silanization) to functionalize tantalum surfaces with a cell adhesive RGD peptide. Surfaces were used untreated or activated with either HNO3 or UV/ozone treatments. The process of biofunctionalization was characterized by means of physicochemical and biological methods. Physisorption of the RGD peptide on control and HNO3-treated tantalum surfaces significantly enhanced the attachment and spreading of osteoblast-like cells; however, no effect on cell adhesion was observed in ozone-treated samples. This effect was attributed to the inefficient binding of the peptide on these highly hydrophilic surfaces, as evidenced by contact angle measurements and X-ray photoelectron spectroscopy. In contrast, activation of tantalum with UV/ozone proved to be the most efficient method to support silanization and subsequent peptide attachment, displaying the highest values of cell adhesion. This study demonstrates that both physical adsorption and silanization are feasible methods to immobilize peptides onto tantalum-based materials, providing them with superior bioactivity.

Fatigue life of bioactive titanium dental implants treated by means of grit-blasting and thermo-chemical treatment.

OBJECTIVE: This study focuses on the fatigue behavior of titanium dental implants as-received, with a grit-blasted surface and with a new bioactive surface treatment (2Steps). BACKGROUND: The 2Step process consists of (1) an initial grit-blasting process to produce a micro-rough surface, followed by (2) a combined thermo-chemical treatment that produces a potentially bioactive surface, that is, that can form an apatitic layer when exposed to biomimetic conditions in vitro. The 2Step treatment produced micro-rough and apatitic coating implants. METHODS: Residual stresses were determined by means of X-ray diffraction. The fatigue tests were carried out at 37°C on 500 dental implants, and the S-N curve was determined. The fatigue-crack nucleation for the different treatments was analyzed. RESULTS: The fatigue tests show that the grit-blasting process improves the fatigue life. This is a consequence of the layer of compressive residual stresses that the treatment generates in titanium surfaces. Dental implants that had its surfaced prepared with the 2Step procedure (grit-blasting and thermo-chemical treatment) had its fatigue life decreased by 10% due to the incorporation of oxygen to the surface and the relaxation of the compressive residual stress produced by the heat treatment. CONCLUSIONS: Thermo-chemical treatment is an excellent compromise between the improvement of bioactive and mechanical long-life behaviors.

Novel peptide-based platform for the dual presentation of biologically active peptide motifs on biomaterials.

Biofunctionalization of metallic materials with cell adhesive molecules derived from the extracellular matrix is a feasible approach to improve cell-material interactions and enhance the biointegration of implant materials (e.g., osseointegration of bone implants). However, classical biomimetic strategies may prove insufficient to elicit complex and multiple biological signals required in the processes of tissue regeneration. Thus, newer strategies are focusing on installing multifunctionality on biomaterials. In this work, we introduce a novel peptide-based divalent platform with the capacity to simultaneously present distinct bioactive peptide motifs in a chemically controlled fashion. As a proof of concept, the integrin-binding sequences RGD and PHSRN were selected and introduced in the platform. The biofunctionalization of titanium with this platform showed a positive trend towards increased numbers of cell attachment, and statistically higher values of spreading and proliferation of osteoblast-like cells compared to control noncoated samples. Moreover, it displayed statistically comparable or improved cell responses compared to samples coated with the single peptides or with an equimolar mixture of the two motifs. Osteoblast-like cells produced higher levels of alkaline phosphatase on surfaces functionalized with the platform than on control titanium; however, these values were not statistically significant. This study demonstrates that these peptidic structures are versatile tools to convey multiple biofunctionality to biomaterials in a chemically defined manner.

A bioactive elastin-like recombinamer reduces unspecific protein adsorption and enhances cell response on titanium surfaces.

We present the immobilization on synthetic substrates of elastin-like recombinamers (ELR) that combine a bioactive motif for cell adhesion with protein antifouling properties. Physical adsorption of the recombinamers and covalent-grafting through organosilane chemistry were investigated. The biochemically-modified surfaces were thoroughly characterized and tested for protein absorption in serum by fluorescence-labelling, XPS, Ellipsometry, and OWLS. The ELR were successfully grafted and stable, even upon mechanical stresses; being the covalent bonding favourable over physical adsorption. The coated metal surfaces exhibited excellent reduction of serum protein adsorption (9 ng/cm(2)) compared to the bare metal surface (310 ng/cm(2)). Non-specific protein adsorption may mask the introduced bioactive motifs; therefore, the bioactivated surfaces should display serum-protein antifouling properties. Finally, improved hMSCs response was assessed on the bioactivated substrates. In summary, the coatings simultaneously displayed anti-fouling and bioactive properties. These studies investigated key factors to enhance tissue material interactions fundamental for the design of bioactive devices and future biomedical applications.