Comparison of the Antibacterial Effect of Silver Nanoparticles and a Multifunctional Antimicrobial Peptide on Titanium Surface.

Titanium implantation success may be compromised by Staphylococcus aureus surface colonization and posterior infection. To avoid this issue, different strategies have been investigated to promote an antibacterial character to titanium. In this work, two antibacterial agents (silver nanoparticles and a multifunctional antimicrobial peptide) were used to coat titanium surfaces. The modulation of the nanoparticle (≈32.1 ± 9.4 nm) density on titanium could be optimized, and a sequential functionalization with both agents was achieved through a two-step functionalization method by means of surface silanization. The antibacterial character of the coating agents was assessed individually as well as combined. The results have shown that a reduction in bacteria after 4 h of incubation can be achieved on all the coated surfaces. After 24 h of incubation, however, the individual antimicrobial peptide coating was more effective than the silver nanoparticles or their combination against Staphylococcus aureus. All tested coatings were non-cytotoxic for eukaryotic cells.

Dual-Action Effect of Gallium and Silver Providing Osseointegration and Antibacterial Properties to Calcium Titanate Coatings on Porous Titanium Implants.

Previously, functional coatings on 3D-printed titanium implants were developed to improve their biointegration by separately incorporating Ga and Ag on the biomaterial surface. Now, a thermochemical treatment modification is proposed to study the effect of their simultaneous incorporation. Different concentrations of AgNO3 and Ga(NO3)3 are evaluated, and the obtained surfaces are completely characterized. Ion release, cytotoxicity, and bioactivity studies complement the characterization. The provided antibacterial effect of the surfaces is analyzed, and cell response is assessed by the study of SaOS-2 cell adhesion, proliferation, and differentiation. The Ti surface doping is confirmed by the formation of Ga-containing Ca titanates and nanoparticles of metallic Ag within the titanate coating. The surfaces generated with all combinations of AgNO3 and Ga(NO3)3 concentrations show bioactivity. The bacterial assay confirms a strong bactericidal impact achieved by the effect of both Ga and Ag present on the surface, especially for Pseudomonas aeruginosa, one of the main pathogens involved in orthopedic implant failures. SaOS-2 cells adhere and proliferate on the Ga/Ag-doped Ti surfaces, and the presence of gallium favors cell differentiation. The dual effect of both metallic agents doping the titanium surface provides bioactivity while protecting the biomaterial from the most frequent pathogens in implantology.

Quantification of Plasma-Produced Hydroxyl Radicals in Solution and their Dependence on the pH.

HO radicals are the most important reactive species generated during water treatment by non-thermal plasma devices. In this letter, we report the first quantification of the steady-state concentration and lifetime of plasma-produced hydroxyl radicals in water solutions at pH 3 and 7, and we discuss the differences based on their reactivity with other plasma-generated species. Finally, we show to what extent the use of chemical probes to quantify short-lived reactive species has an influence on the results and that it should be taken into account.

Chemically Diverse Multifunctional Peptide Platforms with Antimicrobial and Cell Adhesive Properties.

Bacterial infections and incomplete biomaterial integration are major problems that can lead to the failure of medical implants. However, simultaneously addressing these two issues remains a challenge. Here, we present a chemical peptide library based on a multifunctional platform containing the antimicrobial peptide LF1-11 and the cell-adhesive motif RGD. The scaffolds were customized with catechol groups to ensure straightforward functionalization of the implant surface, and linkers of different length to assess the effect of peptide accessibility on the biological response. The peptidic platforms significantly improved the adhesion of mesenchymal stem cells and showed antimicrobial effects against Staphylococcus aureus. Of note is that peptides bearing spacers that were too long displayed the lowest efficiency. Subsequently, we designed a platform replacing linear RGD by cyclic RGD; this further enhanced eukaryotic cell adhesion while retaining excellent antimicrobial properties, thus being a suitable candidate for tissue engineering applications.

Computed tomography and histological evaluation of xenogenic and biomimetic bone grafts in three-wall alveolar defects in minipigs.

OBJECTIVES: This study aimed to compare the performance of a xenograft (XG) and a biomimetic synthetic graft (SG) in three-wall alveolar defects in minipigs by means of 3D computerised tomography and histology. MATERIALS AND METHODS: Eight minipigs were used. A total of eight defects were created in the jaw of each animal, three of which were grafted with XGs, three with SGs, and two were left empty as a negative control. The allocation of the different grafts was randomised. Four animals were euthanised at 6 weeks and four at 12 weeks. The grafted volume was then measured by spiral computed tomography to assess volume preservation. Additionally, a histological analysis was performed in undecalcified samples by backscattered scanning electron microscopy and optical microscopy after Masson's trichrome staining. RESULTS: A linear mixed-effects model was applied considering four fixed factors (bone graft type, regeneration time, anatomic position, and maxilla/mandible) and one random factor (animal). The SG exhibited significantly larger grafted volume (19%) than the XG. The anterior sites preserved better the grafted volume than the posterior ones. Finally, regeneration time had a positive effect on the grafted volume. Histological observations revealed excellent osseointegration and osteoconductive properties for both biomaterials. Some concavities found in the spheroidal morphologies of SGs were associated with osteoclastic resorption. CONCLUSIONS: Both biomaterials met the requirements for bone grafting, i.e. biocompatibility, osseointegration, and osteoconduction. Granule morphology was identified as an important factor to ensure a good volume preservation. CLINICAL RELEVANCE: Whereas both biomaterials showed excellent osteoconduction, SGs resulted in better volume preservation.

Use of three-dimensionally printed ß-tricalcium phosphate synthetic bone graft combined with recombinant human bone morphogenic protein-2 to treat a severe radial atrophic nonunion in a Yorkshire terrier.

OBJECTIVE: To describe a novel surgical approach to treat a critical-sized bone defect due to severe, radial atrophic nonunion in a miniature dog. STUDY DESIGN: Case report ANIMAL: A 1-year-old Yorkshire terrier with a critical-sized left radial defect after failed internal fixation of a transverse radial fracture. METHODS: Computed tomographic (CT) images of the radius were imported for three-dimensional (3D) printing of a custom-designed synthetic 3D-printed ß-tricalcium phosphate (ß-TCP) scaffold. The radius was exposed, and the ß-TCP scaffold was press-fitted in the bone gap underneath the plate. Recombinant human bone morphogenic protein-2 (RhBMP-2) collagen sponges were squeezed to soak the scaffold with growth factor and then placed on both sides of the synthetic graft. Two additional cortical screws were also placed prior to routine closure of the surgical site. RESULTS: Radiographic examination was consistent with complete healing of the radius defect 4 months after surgery. The bone plate was removed 10 months after surgery. According to CT examination 18 months after surgery, there was no evidence of the synthetic graft; instead, complete corticalization of the affected area was noted. Complete functional recovery was observed until the last clinical follow-up 36 months postoperatively. CONCLUSION: Screw fixation and use of a 3D-printed ceramic scaffold augmented with rhBMP-2 resulted in excellent bone regeneration of the nonunion and full recovery of a miniature breed dog. CLINICAL SIGNIFICANCE: The therapeutic approach used in this dog could be considered as an option for treatment of large-bone defects in veterinary orthopedics, especially for defects affecting the distal radius of miniature dogs.

A Dual Molecular Biointerface Combining RGD and KRSR Sequences Improves Osteoblastic Functions by Synergizing Integrin and Cell-Membrane Proteoglycan Binding.

Synergizing integrin and cell-membrane heparan sulfate proteoglycan signaling on biomaterials through peptidic sequences is known to have beneficial effects in the attachment and behavior of osteoblasts; however, controlling the exact amount and ratio of peptides tethered on a surface is challenging. Here, we present a dual molecular-based biointerface combining integrin (RGD) and heparin (KRSR)-binding peptides in a chemically controlled fashion. To this end, a tailor-made synthetic platform (PLATF) was designed and synthesized by solid-phase methodologies. The PLATF and the control linear peptides (RGD or KRSR) were covalently bound to titanium via silanization. Physicochemical characterization by means of contact angle, Raman spectroscopy and XPS proved the successful and stable grafting of the molecules. The biological potential of the biointerfaces was measured with osteoblastic (Saos-2) cells both at short and long incubation periods. Biomolecule grafting (either the PLATF, RGD or KRSR) statistically improved (p < 0.05) cell attachment, spreading, proliferation and mineralization, compared to control titanium. Moreover, the molecular PLATF biointerface synergistically enhanced mineralization (p < 0.05) of Saos-2 cells compared to RGD or KRSR alone. These results indicate that dual-function coatings may serve to improve the bioactivity of medical implants by mimicking synergistic receptor binding.

The Effect of the Thermosensitive Biodegradable PLGA⁻PEG⁻PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement.

The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA⁻PEG⁻PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA⁻PEG⁻PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA⁻PEG⁻PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.

Extent and mechanism of phase separation during the extrusion of calcium phosphate pastes.

The aim of this study was to increase understanding of the mechanism and dominant drivers influencing phase separation during ram extrusion of calcium phosphate (CaP) paste for orthopaedic applications. The liquid content of extrudate was determined, and the flow of liquid and powder phases within the syringe barrel during extrusion were observed, subject to various extrusion parameters. Increasing the initial liquid-to-powder mass ratio, LPR, (0.4-0.45), plunger rate (5-20 mm/min), and tapering the barrel exit (45°-90°) significantly reduced the extent of phase separation. Phase separation values ranged from (6.22 ± 0.69 to 18.94 ± 0.69 %). However altering needle geometry had no significant effect on phase separation. From powder tracing and liquid content determination, static zones of powder and a non-uniform liquid distribution was observed within the barrel. Measurements of extrudate and paste LPR within the barrel indicated that extrudate LPR remained constant during extrusion, while LPR of paste within the barrel decreased steadily. These observations indicate the mechanism of phase separation was located within the syringe barrel. Therefore phase separation can be attributed to either; (1) the liquid being forced downstream by an increase in pore pressure as a result of powder consolidation due to the pressure exerted by the plunger or (2) the liquid being drawn from paste within the barrel, due to suction, driven by dilation of the solids matrix at the barrel exit. Differentiating between these two mechanisms is difficult; however results obtained suggest that suction is the dominant phase separation mechanism occurring during extrusion of CaP paste.

Porosity prediction of calcium phosphate cements based on chemical composition.

The porosity of calcium phosphate cements has an impact on several important parameters, such as strength, resorbability and bioactivity. A model to predict the porosity for biomedical cements would hence be a useful tool. At the moment such a model only exists for Portland cements. The aim of this study was to develop and validate a first porosity prediction model for calcium phosphate cements. On the basis of chemical reaction, molar weight and density of components, a volume-based model was developed and validated using calcium phosphate cement as model material. 60 mol% ß-tricalcium phosphate and 40 mol% monocalcium phosphate monohydrate were mixed with deionized water, at different liquid-to-powder ratios. Samples were set for 24 h at 37°C and 100% relative humidity. Thereafter, samples were dried either under vacuum at room temperature for 24 h or in air at 37 °C for 7 days. Porosity and phase composition were determined. It was found that the two drying protocols led to the formation of brushite and monetite, respectively. The model was found to predict well the experimental values and also data reported in the literature for apatite cements, as deduced from the small absolute average residual errors (<2.0%). In conclusion, a theoretical model for porosity prediction was developed and validated for brushite, monetite and apatite cements. The model gives a good estimate of the final porosity and has the potential to be used as a porosity prediction tool in the biomedical cement field.

Development and Characterization of Biphasic Hydroxyapatite/ß-TCP Cements.

Biphasic calcium phosphate bioceramics composed of hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP) have relevant properties as synthetic bone grafts, such as tunable resorption, bioactivity, and intrinsic osteoinduction. However, they have some limitations associated to their condition of high-temperature ceramics. In this work self-setting Biphasic Calcium Phosphate Cements (BCPCs) with different HA/ß-TCP ratios were obtained from self-setting α-TCP/ß-TCP pastes. The strategy used allowed synthesizing BCPCs with modulated composition, compressive strength, and specific surface area. Due to its higher solubility, α-TCP was fully hydrolyzed to a calcium-deficient HA (CDHA), whereas ß-TCP remained unreacted and completely embedded in the CDHA matrix. Increasing amounts of the non-reacting ß-TCP phase resulted in a linear decrease of the compressive strength, in association to the decreasing amount of precipitated HA crystals, which are responsible for the mechanical consolidation of apatitic cements. Ca2+ release and degradation in acidic medium was similar in all the BCPCs within the timeframe studied, although differences might be expected in longer term studies once ß-TCP, the more soluble phase was exposed to the surrounding media.

Biomimetic treatment on dental implants for short-term bone regeneration.

OBJECTIVES: The main purpose of this work was to assess the short-term bone regenerative potential of new osteoconductive implants. The novelty of the study lies in the analysis of the effectiveness of a novel two-step treatment which combines shot-blasting with a thermo-chemical treatment, at very short times after implant placement in a minipig model. MATERIALS AND METHODS: Three hundred twenty implants with four different surface treatments, namely bioactivated surfaces, micro-rough grit-blasted, micro-rough acid-etched and smooth as-machined titanium implants were placed into the bone of 20 minipigs. The percent of bone-to-implant contact was determined 3 days, 1, 2, 3 and 10 weeks after implant placement by histomorphometric analysis. Surface composition, topography and wettability of the implant specimens were analysed. RESULTS: The combination of shot-blasting and thermo-chemical treatment accelerated bone regeneration at early stages in comparison with all other treatments between day 3 and week 3 (p < 0.05). The value of osseointegration attained at week 2 was maintained until the end of the experiment without any significant changes (percent direct contact ≈ 85 %). This was mostly attributed to the ability of these implants to form in vivo a layer of apatitic mineral that coated the implant and could rapidly stimulate bone nucleation and growth from the implant surface. CONCLUSIONS: The surface quality resulting from this treatment on cpTi provided dental implants with a unique ability of rapid bone regeneration and osseointegration. CLINICAL RELEVANCE: This treatment represents a step forward in the direction of reducing the time prior to implant loading.

Toughening 3D printed biomimetic hydroxyapatite scaffolds: Polycaprolactone-based self-hardening inks.

The application of 3D printing to calcium phosphates has opened unprecedented possibilities for the fabrication of personalized bone grafts. However, their biocompatibility and bioactivity are counterbalanced by their high brittleness. In this work we aim at overcoming this problem by developing a self-hardening ink containing reactive ceramic particles in a polycaprolactone solution instead of the traditional approach that use hydrogels as binders. The presence of polycaprolactone preserved the printability of the ink and was compatible with the hydrolysis-based hardening process, despite the absence of water in the ink and its hydrophobicity. The microstructure evolved from a continuous polymeric phase with loose ceramic particles to a continuous network of hydroxyapatite nanocrystals intertwined with the polymer, in a configuration radically different from the polymer/ceramic composites obtained by fused deposition modelling. This resulted in the evolution from a ductile behavior, dominated by the polymer, to a stiffer behavior as the ceramic phase reacted. The polycaprolactone binder provides two highly relevant benefits compared to hydrogel-based inks. First, the handleability and elasticity of the as-printed scaffolds, together with the proven possibility of eliminating the solvent, opens the door to implanting the scaffolds freshly printed once lyophilized, while in a ductile state, and the hardening process to take place inside the body, as in the case of calcium phosphate cements. Second, even with a hydroxyapatite content of more than 92 wt.%, the flexural strength and toughness of the scaffolds after hardening are twice and five times those of the all-ceramic scaffolds obtained with the hydrogel-based inks, respectively. STATEMENT OF SIGNIFICANCE: Overcoming the brittleness of ceramic scaffolds would extend the applicability of synthetic bone grafts to high load-bearing situations. In this work we developed a 3D printing ink by replacing the conventional hydrogel binder with a water-free polycaprolactone solution. The presence of polycaprolactone not only enhanced significantly the strength and toughness of the scaffolds while keeping the proportion of bioactive ceramic phase larger than 90 wt.%, but it also conferred flexibility and manipulability to the as-printed scaffolds. Since they are able to harden upon contact with water under physiological conditions, this opens up the possibility of implanting them immediately after printing, while they are still in a ductile state, with clear advantages for fixation and press-fit in the bone defect.

Three-Dimensional Printed Patient-Specific Vestibular Augmentation: A Case Report.

Background: The anterior maxilla is challenging regarding aesthetic rehabilitation. Current bone augmentation techniques are complex and 3D-printed bioceramic bone grafts can simplify the intervention. Aim: A four-teeth defect in the anterior maxilla was reconstructed with a 3D-printed synthetic patient-specific bone graft in a staged approach for dental implant delivery. Methods: The bone graft was designed using Cone-Beam Computed Tomography (CBCT) images. The bone graft was immobilized with fixation screws. Bone augmentation was measured on CBCT images at 11 days and 8 and 13 months post-surgery. A biopsy sample was retrieved at reentry (10 months post-augmentation) and evaluated by histological and micro-computed tomography assessments. The definitive prosthesis was delivered 5 months post-reentry and the patient attended a visit 1-year post-loading. Results: A total bone width of 8 mm was achieved (3.7 mm horizontal bone gain). The reconstructed bone remained stable during the healing period and was sufficient for placing two dental implants (with an insertion torque > 35 N·cm). The fractions of new bone, bone graft, and soft tissue in the biopsy were 40.77%, 41.51%, and 17.72%, respectively. The histological assessment showed no signs of encapsulation, and mature bone was found in close contact with the graft, indicating adequate biocompatibility and suggesting osteoconductive properties of the graft. At 1-year post-loading, the soft tissues were healthy, and the dental implants were stable. Conclusions: The anterior maxilla's horizontal ridge can be reconstructed using a synthetic patient-specific 3D-printed bone graft in a staged approach for implant placement. The dental implants were stable and successful 1-year post-loading.

Redefining biomaterial biocompatibility: challenges for artificial intelligence and text mining.

The surge in 'Big data' has significantly influenced biomaterials research and development, with vast data volumes emerging from clinical trials, scientific literature, electronic health records, and other sources. Biocompatibility is essential in developing safe medical devices and biomaterials to perform as intended without provoking adverse reactions. Therefore, establishing an artificial intelligence (AI)-driven biocompatibility definition has become decisive for automating data extraction and profiling safety effectiveness. This definition should both reflect the attributes related to biocompatibility and be compatible with computational data-mining methods. Here, we discuss the need for a comprehensive and contemporary definition of biocompatibility and the challenges in developing one. We also identify the key elements that comprise biocompatibility, and propose an integrated biocompatibility definition that enables data-mining approaches.

Gallium and silver-doped titanium surfaces provide enhanced osteogenesis, reduce bone resorption and prevent bacterial infection in co-culture.

Bacterial infection remains a significant problem associated with orthopaedic surgeries leading to surgical site infection (SSI). This unmet medical need can become an even greater complication when surgery is due to malignant bone tumor. In the present study, we evaluated in vitro titanium (Ti) implants subjected to gallium (Ga) and silver (Ag)-doped thermochemical treatment as strategy to prevent SSI and improve osteointegration in bone defects caused by diseases such as osteoporosis, bone tumor, or bone metastasis. Firstly, as Ga has been reported to be an osteoinductive and anti-resorptive agent, its performance in the mixture was proved by studying human mesenchymal stem cells (hMSC) and pre-osteoclasts (RAW264.7) behaviour. Then, the antibacterial potential provided by Ag was assessed by resembling "The Race for the Surface" between hMSC and Pseudomonas aeruginosa in two co-culture methods. Moreover, the presence of quorum sensing molecules in the co-culture was evaluated. The results highlighted the suitability of the mixture to induce osteodifferentiation and reduce osteoclastogenesis in vitro. Furthermore, the GaAg surface promoted strong survival rate and retained osteoinduction potential of hMSCs even after bacterial inoculation. Therefore, GaAg-modified titanium may be an ideal candidate to repair bone defects caused by excessive bone resorption, in addition to preventing SSI. STATEMENT OF SIGNIFICANCE: This article provides important insights into titanium for fractures caused by osteoporosis or bone metastases with high incidence in surgical site infection (SSI) because in this situation bacterial infection can become a major disaster. In order to solve this unmet medical need, we propose a titanium implant modified with gallium and silver to improve osteointegration, reduce bone resorption and avoid bacterial infection. For that aim, we study osteoblast and osteoclast behavior with the main novelty focused on the antibacterial evaluation. In this work, we recreate "the race for the surface" in long-term experiments and study bacterial virulence factors (quorum sensing). Therefore, we believe that our article could be of great interest, providing a great impact on future orthopedic applications.

Phase composition of calcium phosphate materials affects bone formation by modulating osteoclastogenesis.

Human mesenchymal stromal cells (hMSCs) seeded on calcium phosphate (CaP) bioceramics are extensively explored in bone tissue engineering and have recently shown effective clinical outcomes. In previous pre-clinical studies, hMSCs-CaP-mediated bone formation was preceded by osteoclastogenesis at the implantation site. The current study evaluates to what extent phase composition of CaPs affects the osteoclast response and ultimately influence bone formation. To this end, four different CaP bioceramics were used, hydroxyapatite (HA), ß-tricalcium phosphate (ß-TCP) and two biphasic composites of HA/ß-TCP ratios of 60/40 and 20/80 respectively, for in vitro osteoclast differentiation and correlation with in vivo osteoclastogenesis and bone formation. All ceramics allowed osteoclast formation in vitro from mouse and human precursors, except for pure HA, which significantly impaired their maturation. Ectopic implantation alongside hMSCs in subcutis sites of nude mice revealed new bone formation at 8 weeks in all conditions with relative amounts for ß-TCP > biphasic CaPs > HA. Surprisingly, while hMSCs were essential for osteoinduction, their survival did not correlate with bone formation. By contrast, the degree of early osteoclastogenesis (2 weeks) seemed to define the extent of subsequent bone formation. Together, our findings suggest that the osteoclastic response could be used as a predictive marker in hMSC-CaP-based bone regeneration and strengthens the need to understand the underlying mechanisms for future biomaterial development. STATEMENT OF SIGNIFICANCE: The combination of mesenchymal stromal cells (MSCs) and calcium phosphate (CaP) materials has demonstrated its safety and efficacy for bone regeneration in clinical trials, despite our insufficient understanding of the underlying biological mechanisms. Osteoclasts were previously suggested as key mediators between the early inflammatory phase following biomaterial implantation and the subsequent bone formation. Here we compared the affinity of osteoclasts for various CaP materials with different ratios of hydroxyapatite to ß-tricalcium phosphate. We found that osteoclast formation, both in vitro and at early stages in vivo, correlates with bone formation when the materials were implanted alongside MSCs in mice. Surprisingly, MSC survival did not correlate with bone formation, suggesting that the number or phenotype of osteoclasts formed was more important.

De Novo Design of Integrin α5ß1 Modulating Proteins for Regenerative Medicine.

Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-coated titanium implants outperformed fibronectin and RGD-coated implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine. One-Sentence Summary: A de novo-designed fibronectin substitute, NeoNectin, is specific for integrin α5ß1 and can be incorporated into biomaterials for regenerative medicine.

Injectable collagen/α-tricalcium phosphate cement: collagen-mineral phase interactions and cell response.

A bone inspired material was obtained by incorporating collagen in the liquid phase of an α-tricalcium phosphate cement, either in solubilized or in fibrilized form. This material was able to set in situ, giving rise to a calcium deficient hydroxyapatite (CDHA)/collagen composite. The morphology and distribution of collagen in the composite was shown to be strongly affected by the collagen pre-treatment. The interactions between collagen and the inorganic phase were assessed by FTIR. A red shift of the amide I band was indicative of calcium chelation by the collagen carbonyl groups. The rate of CDHA formation was not affected when diluted collagen solutions (1 mg/ml) were used, whereas injectability improved. The presence of solubilized collagen, even in low amount (1 %), increased cell adhesion and proliferation on the composites. Still in the absence of osteogenic medium, significant ALP activity was detected both in the inorganic and the collagen-containing cements. The maximum ALP activity was advanced in the collagen-containing cement as compared to the inorganic cement.

High-aspect-ratio nanostructured hydroxyapatite: towards new functionalities for a classical material.

Hydroxyapatite-based materials have been widely used in countless applications, such as bone regeneration, catalysis, air and water purification or protein separation. Recently, much interest has been given to controlling the aspect ratio of hydroxyapatite crystals from bulk samples. The ability to exert control over the aspect ratio may revolutionize the applications of these materials towards new functional materials. Controlling the shape, size and orientation of HA crystals allows obtaining high aspect ratio structures, improving several key properties of HA materials such as molecule adsorption, ion exchange, catalytic reactions, and even overcoming the well-known brittleness of ceramic materials. Regulating the morphogenesis of HA crystals to form elongated oriented fibres has led to flexible inorganic synthetic sponges, aerogels, membranes, papers, among others, with applications in sustainability, energy and catalysis, and especially in the biomedical field.