Improving Hydrophilicity and Inducing Bone-Like Apatite Formation on PPBES by Polydopamine Coating for Biomedical Application.

Copoly(phthalazinone biphenyl ether sulfone) (PPBES) as a commercially available polyarylether is a promising orthopaedic implant material because its mechanical properties are similar to bone. However, the bioinert surface of polyarylether causes some clinical problems after implantation, which limits its application as an implant material. In this study, the surface of PPBES was modified by a biomineralization method of polydopamine-assisted hydroxyapatite formation (pHAF) to enhance its cytocompatibility. Polydopamine (PDA) coating, inspired by the adhesion mechanism of mussels, can readily endow PPBES with high hydrophilicity and the ability to integrate via the bone-like apatite coating. PPBES and PDA-coated PPBES were evaluated by scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. The water contact angles were reduced significantly after coating with PDA. PDA was successfully synthesized on PPBES and more PDA was obtained by increasing the temperature. Bone-like apatite on PPBES (apatite-coated PPBES) was confirmed by SEM and transmission electron microscopy (TEM). The cytotoxicity of pristine PPBES and apatite-coated PPBES were characterized by culturing of NIH-3T3 cells. Bone-like apatite synthesized by pHAF could further enhance cytocompatibility in vitro. This study provides a promising alternative for biofunctionalized PPBES with improved cytocompatibility for bone implant application.

From solvent-free microspheres to bioactive gradient scaffolds.

A solvent-free microsphere sintering technique was developed to fabricate scaffolds with pore size gradient for tissue engineering applications. Poly(D,L-Lactide) microspheres were fabricated through an emulsification method where TiO2 nanoparticles were employed both as particulate emulsifier in the preparation procedure and as surface modification agent to improve bioactivity of the scaffolds. A fine-tunable pore size gradient was achieved with a pore volume of 30±2.6%. SEM, EDX, XRD and FTIR analyses all confirmed the formation of bone-like apatite at the 14th day of immersion in Simulated Body Fluid (SBF) implying the ability of our scaffolds to bond to living bone tissue. In vitro examination of the scaffolds showed progressive activity of the osteoblasts on the scaffold with evidence of increase in its mineral content. The bioactive scaffold developed in this study has the potential to be used as a suitable biomaterial for bone tissue engineering and hard tissue regeneration.

Graphene Oxide Functionalized Gelatin Methacryloyl Microgel for Enhanced Biomimetic Mineralization and in situ Bone Repair.

Introduction: The formation of bone-like apatite (Ap) on natural polymers through biomimetic mineralization using simulated body fluid (SBF) can improve osteoconductivity and biocompatibility, while lowering immunological rejection. Nonetheless, the coating efficiency of the bone-like Ap layer on natural polymers requires improvement. Carbonyls (-COOH) and hydroxyls (-OH) are abundant in graphene oxide (GO), which may offer more active sites for biomimetic mineralization and promote the proliferation of rat bone marrow stromal cells (BMSCs). Methods: In this study, gelatin methacryloyl (GelMA) microgels were infused with GO (0, 0.5, 1, and 2 mg/mL) and embedded into microgels in SBF for 1, 7, and 14 days. Systematic in vitro and in vivo experiments were performed to evaluate the structure of the microgel and its effect on cell proliferation and ability to repair bone defects in rats. Results: The resulting GO-GelMA-Ap microgels displayed a porous, interconnected structure with uniformly coated surfaces in bone-like Ap, and the Ca/P ratio of the 1 mg/mL GO-GelMA-Ap group was comparable to that of natural bone tissue. Moreover, the 1 mg/mL GO-GelMA-Ap group exhibited a greater Ap abundance, enhanced proliferation of BMSCs in vitro and increased bone formation in vivo compared to the GelMA-Ap group. Discussion: Overall, this study offers a novel method for incorporating GO into microgels for bone tissue engineering to promote biomimetic mineralization.

Mussel-Inspired Surface Functionalization of Porous Albumin Cryogels Supporting Synergistic Antibacterial/Antioxidant Activity and Bone-Like Apatite Formation.

A crucial method for adding new functions to current biomaterials for biomedical applications has been surface functionalization via molecular design. Mussel-inspired polydopamine (PDA) has generated much attention as a facile method for the functionalization of biomaterials because of its substantial independence in deposition, beneficial cell interactions, and significant responsiveness aimed at secondary functionalization. Because of their porous structure, the bovine serum albumin methacryloyl (BSAMA)-BM cryogels were functionalized with PDA (BM-PDA), which may reproduce the architecture and biological purpose of the natural extracellular environment. Excellent antioxidative and antibacterial qualities, improved mineralization, and better cell responsiveness were all demonstrated by BM-PDA. BM-PDA scaffolds maintained their linked and uniform pores after functionalization, which can make it easier for nutrients to be transported during bone repair. As a result, hydroxyapatite (HA)-coated BM* and BM-PDA* cryogels were created through successive mineralization with the goal of mineralized bone tissue repair. The heterogeneous nucleation and surface roughness contributed to rod-like apatite production in BM-PDA* cryogels whereas BM* cryogels were made up of plate-like HA morphologies. Analysis results showed that after five cycles, the mineral contents were around 57% and the HA units remained equally dispersed on the surface of BM-PDA* with a Ca/P ratio of 1.63. Other natural polymer-based cryogels can be coated using this general, rapid, and simple PDA coating technique and utilized as implants for bone tissue engineering. Future clinical uses of albumin cryogels for bone tissue engineering will advance as a result of additional in-vivo testing of such PDA-coated cryogels.

Assessment of Titanate Nanolayers in Terms of Their Physicochemical and Biological Properties.

The surface modification of titanium substrates and its alloys in order to improve their osseointegration properties is one of widely studied issues related to the design and production of modern orthopedic and dental implants. In this paper, we discuss the results concerning Ti6Al4V substrate surface modification by (a) alkaline treatment with a 7 M NaOH solution, and (b) production of a porous coating (anodic oxidation with the use of potential U = 5 V) and then treating its surface in the abovementioned alkaline solution. We compared the apatite-forming ability of unmodified and surface-modified titanium alloy in simulated body fluid (SBF) for 1-4 weeks. Analysis of the X-ray diffraction patterns of synthesized coatings allowed their structure characterization before and after immersing in SBF. The obtained nanolayers were studied using Raman spectroscopy, diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), and scanning electron microscopy (SEM) images. Elemental analysis was carried out using X-ray energy dispersion spectroscopy (SEM EDX). Wettability and biointegration activity (on the basis of the degree of integration of MG-63 osteoblast-like cells, L929 fibroblasts, and adipose-derived mesenchymal stem cells cultured in vitro on the sample surface) were also evaluated. The obtained results proved that the surfaces of Ti6Al4V and Ti6Al4V covered by TiO2 nanoporous coatings, which were modified by titanate layers, promote apatite formation in the environment of body fluids and possess optimal biointegration properties for fibroblasts and osteoblasts.

Effect of doping different Si source on Ca-P bioceramic coating fabricated by laser cladding.

The doping of silicon (Si) has been proved to improve the bioactivity of Ca-P ceramics. In light of this thinking, in the present study, Ca-P coatings with La2O3 by addition of 10 wt% SiO2 and 10 wt% diatomaceous earth (DE) were fabricated by laser cladding on Ti6Al4V, respectively. Coating doped without Si was also fabricated as the comparison group for the experiment. The effect of two different Si sources on the surface morphology, microstructure, microhardness, and bioactivity was systematically studied. The experimental results show that the Si-doped coating is of rough surface morphology, and the addition of DE significantly reduces the number of cracks and improves the microhardness. The X-ray diffraction results reveal that the amount of bioactive phase tricalcium-phosphate (TCP) and hydroxyapatite (HA) reaches maximum in the DE-doped coating. After soaking in simulated body fluid (SBF), the precipitate of bone-like apatite in the DE-doped coating is significantly higher than that of the other coatings.

Polylactide Composite Pins Reinforced with Bioresorbable Continuous Glass Fibers Demonstrating Bone-like Apatite Formation and Spiral Delamination Degradation.

The emergence of polylactide composites reinforced with bioresorbable silicate glass fibers has allowed for the long-term success of biodegradable polymers in load-bearing orthopedic applications. However, few studies have reported on the degradation behavior and bioactivity of such biocomposites. The aim of this work was to investigate the degradation behavior and in vitro bioactivity of a novel biocomposite pin composed of bioresorbable continuous glass fibers and poly-L-D-lactide in simulated body fluid for 78 weeks. As the materials degraded, periodic spiral delamination formed microtubes and funnel-shaped structures in the biocomposite pins. It was speculated that the direction of degradation, from both ends towards the middle of the fibers and from the surface through to the bulk of the polymer matrix, could facilitate bone healing. Following immersion in simulated body fluid, a bone-like apatite layer formed on the biocomposite pins which had a similar composition and structure to natural bone. The sheet- and needle-like apatite nanostructure was doped with sodium, magnesium, and carbonate ions, which acted to lower the Ca/P atomic ratio to less than the stoichiometric apatite and presented a calcium-deficient apatite with low crystallinity. These findings demonstrated the bioactivity of the new biocomposite pins in vitro and their excellent potential for load-bearing applications.

Cell Type Influences Local Delivery of Biomolecules from a Bioinspired Apatite Drug Delivery System.

Recently, the benefit of step-wise sequential delivery of fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 from a bioinspired apatite drug delivery system on mouse calvarial bone repair was demonstrated. The thicknesses of the nanostructured poly-l-Lysine/poly-l-Glutamic acid polyelectrolyte multilayer (PEM) and the bone-like apatite barrier layer that make up the delivery system, were varied. The effects of the structural variations of the coating on the kinetics of cell access to a cytotoxic factor delivered by the layered structure were evaluated. FGF-2 was adsorbed into the outer PEM, and cytotoxic antimycin-A (AntiA) was adsorbed to the substrate below the barrier layer to detect the timing of the cell access. While MC3T3-E1 osteoprogenitor cells accessed AntiA after three days, the RAW 264.7 macrophage access occurred within 4 h, unless the PEM layer was removed, in which case the results were reversed. Pits were created in the coating by the RAW 264.7 macrophages and initiated delivery, while the osteoprogenitor cell access to drugs occurred through a solution-mediated coating dissolution, at junctions between the islands of crystals. Macrophage-mediated degradation is therefore a mechanism that controls drug release from coatings containing bioinspired apatite.

Biodegradation Resistance and Bioactivity of Hydroxyapatite Enhanced Mg-Zn Composites via Selective Laser Melting.

Mg-Zn alloys have attracted great attention as implant biomaterials due to their biodegradability and biomechanical compatibility. However, their clinical application was limited due to the too rapid degradation. In the study, hydroxyapatite (HA) was incorporated into Mg-Zn alloy via selective laser melting. Results showed that the degradation rate slowed down due to the decrease of grain size and the formation of protective layer of bone-like apatite. Moreover, the grain size continually decreased with increasing HA content, which was attributed to the heterogeneous nucleation and increased number of nucleation particles in the process of solidification. At the same time, the amount of bone-like apatite increased because HA could provide favorable areas for apatite nucleation. Besides, HA also enhanced the hardness due to the fine grain strengthening and second phase strengthening. However, some pores occurred owing to the agglomerate of HA when its content was excessive, which decreased the biodegradation resistance. These results demonstrated that the Mg-Zn/HA composites were potential implant biomaterials.

In vitro evaluation for apatite-forming ability of cellulose-based nanocomposite scaffolds for bone tissue engineering.

Research on synthetic bioactive bone graft materials has significantly expanded in the past decade. In this study, the nanocomposite scaffold of semi-interpenetrating networks (semi-IPN) cellulose-graft-polyacrylamide/nano-hydroxyapatite was synthesized through free radical polymerization. The scaffolds were fabricated by the freeze-drying technique. The prepared semi-IPN nanocomposite scaffolds were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis. In addition, the mechanical properties (i.e., elastic modulus and compressive strength) of the scaffolds were investigated. The SEM images showed that the pores of the scaffolds were interconnected, and their sizes ranged from 120 µm to 190 µm. Under optimum conditions, the prepared scaffolds had a compressive strength of 4.80 MPa, an elastic modulus of 0.29 GPa and a value of 47.37% porosity. Furthermore, the apatite-forming ability of the scaffolds was determined using simulated body fluid (SBF) for 28 days. The results revealed that the new apatite particles could grow on the surface of the scaffolds after a 14-day immersion in SBF. Finally, this study suggests that the prepared semi-IPN nanocomposites that closely mimic the properties of bone tissue could be a promising scaffold for bone tissue engineering.

Enhanced apatite-forming ability and antibacterial activity of porous anodic alumina embedded with CaO-SiO2-Ag2O bioactive materials.

In this study, to provide porous anodic alumina (PAA) with bioactivity and anti-bacterial properties, sol-gel derived bioactive CaO-SiO2-Ag2O materials were loaded onto and into PAA nano-pores (termed CaO-SiO2-Ag2O/PAA) by a sol-dipping method and subsequent calcination of the gel-glasses. The in vitro apatite-forming ability of the CaO-SiO2-Ag2O/PAA specimens was evaluated by soaking them in simulated body fluid (SBF). The surface microstructure and chemical property before and after soaking in SBF were characterized. Release of ions into the SBF was also measured. In addition, the antibacterial properties of the samples were tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that CaO-SiO2-Ag2O bioactive materials were successfully decorated onto and into PAA nano-pores. In vitro SBF experiments revealed that the CaO-SiO2-Ag2O/PAA specimens dramatically enhanced the apatite-forming ability of PAA in SBF and Ca, Si and Ag ions were released from the samples in a sustained and slow manner. Importantly, E. coli and S. aureus were both killed on the CaO-SiO2-Ag2O/PAA (by 100%) samples compared to PAA controls after 3 days of culture. In summary, this study demonstrated that the CaO-SiO2-Ag2O/PAA samples possess good apatite-forming ability and high antibacterial activity causing it to be a promising bioactive coating candidate for implant materials for orthopedic applications.

Tuning the surface microstructure of titanate coatings on titanium implants for enhancing bioactivity of implants.

Biological performance of artificial implant materials is closely related to their surface characteristics, such as microtopography, and composition. Therefore, convenient fabrication of artificial implant materials with a cell-friendly surface structure and suitable composition was of great significance for current tissue engineering. In this work, titanate materials with a nanotubular structure were successfully fabricated through a simple chemical treatment. Immersion test in a simulated body fluid and in vitro cell culture were used to evaluate the biological performance of the treated samples. The results demonstrate that the titanate layer with a nanotubular structure on Ti substrates can promote the apatite-inducing ability remarkably and greatly enhance cellular responses. This highlights the potential of such titanate biomaterials with the special nanoscale structure and effective surface composition for biomedical applications such as bone implants.

Bone-like apatite coating on functionalized poly(etheretherketone) surface via tailored silanization layers technique.

Poly(etheretherketone) (PEEK) is a rigid semi-crystalline polymer with outstanding mechanical properties, bone-like stiffness and suitable biocompatibility that has attracted much interest as a biomaterial for orthopedic and dental implants. However, the bio-inert surface of PEEK limits its biomedical applications when direct osteointegration between the implants and the host tissue is desired. In this work, -PO4H2, -COOH and -OH groups were introduced on the PEEK surface by further chemical treatments of the vinyl-terminated silanization layers formed on the hydroxylation-pretreated PEEK surface. Both the surface-functionalized and pristine specimens were characterized by X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and water contact angle measurements. When placed in 1.5 strength simulated body fluid (SBF) solution, apatite was observed to form uniformly on the functionalized PEEK surface and firmly attach to the substrate. The characterized results demonstrated that the coating was constituted by poorly crystallized bone-like apatite and the effect of surface functional groups on coating formation was also discussed in detail. In addition, in vitro biocompatibility of PEEK, in terms of pre-osteoblast cell (MC3T3-E1) attachment, spreading and proliferation, was remarkably enhanced by the bone-like apatite coating. Thus, this study provides a method to enhance the bioactivity of PEEK and expand its applications in orthopedic and dental implants.

Mesoscopically ordered bone-mimetic nanocomposites.

A sustainable approach that highly mimics bone-material deposition is reported to produce mechanically stable, degradable composites with nanostructures resembling that of natural bone. Molecular self-assembly combining intermolecular crosslinking leads to resilient matrices possessing long-range ordered aqueous domains, inside which moderately aligned poorly crystalline apatite is converted from the transient amorphous calcium phosphate phase.

In vitro apatite formation on porous anodic alumina induced by a phosphorylation treatment.

In this study, a phosphorylation treatment of porous anodic alumina (PAA) was performed by wet impregnation in phosphoric acid and a subsequent heat treatment. The PAA and phosphorylated PAA specimens were analyzed using a field emission scanning electron microscope, an energy-dispersive X-ray spectrometer, and Fourier transform infrared spectroscopy. The apatite-forming ability of the phosphorylated PAA was evaluated by soaking the specimens in simulated body fluid for 1, 3, and 7 days. The surface microstructures and chemical property changes after soaking in simulated body fluid were again characterized by field emission scanning electron microscope, energy-dispersive X-ray spectrometer, and Fourier transform infrared spectroscopy. Results of this study demonstrated that the functional -PO4 groups introduced onto the PAA surface dramatically promoted the deposition of bone-like apatite on PAA. The results from this study indicated that the phosphorylation treatment of anodic alumina is an effective method for inducing bone-like apatite formation, and this phosphorylated PAA can be a promising candidate to be used as bioactive surface coatings on implant metals and alloys for orthopedic and dental applications.

Biomimetic growth of bone-like apatite via simulated body fluid on hydroxyethyl cellulose/polyvinyl alcohol electrospun nanofibers.

In this study, randomly oriented hydroxyethyl cellulose/polyvinyl alcohol (HEC/PVA) nanofibers were fabricated by electrospinning. The blend solutions of HEC/PVA with different weight ratio of HEC to PVA were prepared using water as solvent to fabricate nanofibers. These nanofibrous scaffolds were coated with bone-like apatite by immersing into 10x simulated body fluid (SBF) for different time periods. The morphology and structure of the nanofibers were characterized by SEM, FTIR and DSC. FESEM-EDS and FTIR analysis were used to confirm the deposition of apatite on the surface of nanofibers. The results of this study suggest that this apatite coated nanofibrous scaffolds could be a suitable biomaterial for bone tissue engineering.

Preparation of electrospun poly(lactic acid)-based hybrids containing siloxane-doped vaterite particles for bone regeneration.

Siloxane/poly(L-lactic acid)/vaterite hybrid (SiPVH) fibremats constantly release calcium ions and ionic silicon species that have the potential to promote bone regeneration. In order to improve the mechanical properties of the SiPVH fibremats, the effect of various silixane-containing vaterite (denoted by SiV) content (10-60 wt%) on tensile properties was assessed. SiPVH fibremats with 30 wt% SiV content showed the highest tensile strength of 2.87 ± 0.39 MPa. Based on the energy-dissipation mechanism, failure initiated at the stress concentration points such as pores on the fibre surfaces or filler particles. In the case of the SiPVH fibremats with 20 and 30 wt% SiV, stress concentration occurred around the filler particles, where the applied energy was directly converted to small volume dilatation around the filler particles during failure of the fibres. This mechanism can be applied only when the material contains the polymer and the filler particles in specific ratios; 20 and 30 wt% filler content in the fibremat in this work. To coat the fibre surfaces with bone-like apatite SiPVH fibremats were soaked in modified simulated body fluid (1.5 SBF). Bone-like apatite formed on the surfaces of SiPVH fibremats with more than 30 wt% of SiV content in 1 day of soaking. These results reveal that the SiPVH fibremats containing 30 wt% SiV have suitable mechanical properties for bone filler materials.