Nd-induced honeycomb structure of intermetallic phase enhances the corrosion resistance of Mg alloys for bone implants.

Mg-5.6Zn-0.5Zr alloy (ZK60) tends to degrade too rapid for orthopedic application, in spite of its natural degradation, suitable strength and good biocompatibility. In this study, Nd was alloyed with ZK60 via laser melting method to enhance its corrosion resistance. The microstructure features, mechanical properties and corrosion behaviors of ZK60-xNd (x = 0, 1.8, 3.6, 5.4 wt.%) were investigated. Results showed that laser melted ZK60-xNd were composed of fine ɑ-Mg grains and intermetallic phases along grain boundaries. And the precipitated intermetallic phases experienced successive changes: divorced island-like MgZn phase → honeycomb-like T phase → coarsened and agglomerated W phase with Nd increasing. It was worth noting that ZK60-3.6Nd with honeycomb-like T phase exhibited an optimal corrosion behavior with a corrosion rate of 1.56 mm year-1. The improved corrosion behavior was ascribed to: (I) dense surface film caused by the formation of Nd2O3 hindered the invasion of immersion solution; (II) the three-dimensional honeycomb structure of intermetallic phases formed a tight barrier to restrain the propagation of corrosion. Moreover, ZK60-3.6Nd exhibited good biocompatibility. It was suggested that ZK60-3.6Nd was a preferable candidate for biodegradable bone implant.

Functionalization of Calcium Sulfate/Bioglass Scaffolds with Zinc Oxide Whisker.

There are urgent demands for satisfactory antibacterial activity and mechanical properties of bone scaffolds. In this study, zinc oxide whisker (ZnOw) was introduced into calcium sulfate/bioglass scaffolds. Antimicrobial behavior was analyzed using Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The results showed that the scaffolds presented a strong antibacterial activity after introducing ZnOw, due to the antibacterial factors released from the degradation of ZnO. Moreover, ZnOw was also found to have a distinct reinforcing effect on mechanical properties. This was ascribed to whisker pull-out, crack bridging, crack deflection, crack branching and other toughening mechanisms. In addition, the cell culture experiments showed that the scaffolds with ZnOw had a good biocompatibility.

Focal adhesion kinase knockdown in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis via downregulating MCP-1/CCL2 expression.

Carcinoma-associated fibroblasts (CAFs) have been demonstrated to play an important role in the occurrence and development of oral squamous cell carcinoma (OSCC). The aim of this study is to investigate the influence of CAFs on OSCC cells and to explore the role of focal adhesion kinase (FAK) in this process. The results showed that oral CAFs expressed a higher level of FAK than normal human gingival fibroblasts (HGFs), and the conditioned medium (CM) of CAFs could induce the invasion and migration of SCC-25, one oral squamous carcinoma cell line. However, knockdown of FAK by small interfering RNA (siRNA) resulted in inhibition of CAF-CM induced cell invasion and migration in SCC-25, probably by reducing the production of monocyte chemoattractant protein-1 (MCP-1/CCL2), one of downstream target chemokines. Therefore, our findings indicated that targeting FAK in CAFs might be a promising strategy for the treatment of OSCC in the future.

Akermanite scaffolds reinforced with boron nitride nanosheets in bone tissue engineering.

Akermanite (AKM) is considered to be a promising bioactive material for bone tissue engineering due to the moderate biodegradability and excellent biocompatibility. However, the major disadvantage of AKM is the relatively inadequate fracture toughness, which hinders the further applications. In the study, boron nitride nanosheets (BNNSs) reinforced AKM scaffolds are fabricated by selective laser sintering. The effects of BNNSs on the mechanical properties and microstructure are investigated. The results show that the compressive strength and fracture toughness increase significantly with BNNSs increasing from 0.5 to 1.0 wt%. The remarkable improvement is ascribed to pull out and grain wrapping of BNNSs with AKM matrix. While, overlapping sheets is observed when more BNNSs are added, which results in the decline of mechanical properties. In addition, it is found that the composite scaffolds possess good apatite-formation ability when soaking in simulated body fluids, which have been confirmed by energy dispersed spectroscopy and flourier transform infrared spectroscopy. Moreover, MG63 osteoblast-like cells and human bone marrow stromal cells are seeded on the scaffolds. Scanning electron microscopy analysis confirms that both cells adhere and proliferate well, indicating favorable cytocompatibility. All the facts demonstrate the AKM scaffolds reinforced by BNNSs have potential applications for tissue engineering.

Nano SiO2 and MgO improve the properties of porous ß-TCP scaffolds via advanced manufacturing technology.

Nano SiO2 and MgO particles were incorporated into ß-tricalcium phosphate (ß-TCP) scaffolds to improve the mechanical and biological properties. The porous cylindrical ß-TCP scaffolds doped with 0.5 wt % SiO2, 1.0 wt % MgO, 0.5 wt % SiO2 + 1.0 wt % MgO were fabricated via selective laser sintering respectively and undoped ß-TCP scaffold was also prepared as control. The phase composition and mechanical strength of the scaffolds were evaluated. X-ray diffraction analysis indicated that the phase transformation from ß-TCP to α-TCP was inhibited after the addition of MgO. The compressive strength of scaffold was improved from 3.12 ± 0.36 MPa (ß-TCP) to 5.74 ± 0.62 MPa (ß-TCP/SiO2), 9.02 ± 0.55 MPa (ß-TCP/MgO) and 10.43 ± 0.28 MPa (ß-TCP/SiO2/MgO), respectively. The weight loss and apatite-forming ability of the scaffolds were evaluated by soaking them in simulated body fluid. The results demonstrated that both SiO2 and MgO dopings slowed down the degradation rate and improved the bioactivity of ß-TCP scaffolds. In vitro cell culture studies indicated that SiO2 and MgO dopings facilitated cell attachment and proliferation. Combined addition of SiO2 and MgO were found optimal in enhancing both the mechanical and biological properties of ß-TCP scaffold.

Liquid phase sintered ceramic bone scaffolds by combined laser and furnace.

Fabrication of mechanically competent bioactive scaffolds is a great challenge in bone tissue engineering. In this paper, ß-tricalcium phosphate (ß-TCP) scaffolds were successfully fabricated by selective laser sintering combined with furnace sintering. Bioglass 45S5 was introduced in the process as liquid phase in order to improve the mechanical and biological properties. The results showed that sintering of ß-TCP with the bioglass revealed some features of liquid phase sintering. The optimum amount of 45S5 was 5 wt %. At this point, the scaffolds were densified without defects. The fracture toughness, compressive strength and stiffness were 1.67 MPam1/2, 21.32 MPa and 264.32 MPa, respectively. Bone like apatite layer was formed and the stimulation for apatite formation was increased with increase in 45S5 content after soaking in simulated body fluid, which indicated that 45S5 could improve the bioactivity. Furthermore, MG-63 cells adhered and spread well, and proliferated with increase in the culture time.

Current progress in bioactive ceramic scaffolds for bone repair and regeneration.

Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration.

Silicon dioxide nanoparticles decorated on graphene oxide nanosheets and their application in poly(l-lactic acid) scaffold.

INTRODUCTION: The aggregation of graphene oxide (GO) is considered as main challenge, although GO possesses excellent mechanical properties which arouses widespread attention as reinforcement for polymers. OBJECTIVES: In this study, silicon dioxide (SiO2) nanoparticles were decorated onto surface of GO nanosheets through in situ growth method for promoting dispersion of GO in poly(l-lactic acid) (PLLA) bone scaffold. METHODS: Hydroxyl and carboxyl functional groups of GO provided sites for SiO2 nucleation, and SiO2 grew with hydrolysis and polycondensation of tetraethyl orthosilicate (TEOS) and finally formed nanoparticles onto surface of GO with covalent bonds. Then, the GO@ SiO2 nanocomposite was blended with PLLA for the fabrication of bone scaffold by selective laser sintering (SLS). RESULT: The results indicated that the obtained SiO2 were distributed relatively uniformly on surface of GO under TEOS concentration of 0.10 mol/L (GO@SiO2-10), and the covering of SiO2 on GO could increase interlayer distance of GO nanosheets from 0.799 nm to 0.894 nm, thus reducing van der Waals forces between GO nanosheets and facilitating the dispersion. Tensile and compressive strength of scaffold containing GO@SiO2 hybrids were significantly enhanced, especially for the scaffold containing GO@SiO2-10 hybrids with enhancement of 30.95 % in tensile strength and 66.33 % in compressive strength compared with the scaffold containing GO. Additionally, cell adhesion and fluorescence experiments demonstrated excellent cytocompatibility of the scaffold. CONCLUSIONS: The good dispersion of GO@SiO2 enhances the mechanical properties and cytocompatibility of scaffold, making it a potential candidate for bone tissue engineering applications.

A dual redox system for enhancing the biodegradability of Fe-C-Cu composite scaffold.

Fe-based biocomposites are emerging as temporary orthopedic implants due to natural biodegradability and high mechanical strength. Yet, the slow degradation kinetics restricts their biomedical applications. In this work, Cu-initiated redox system was established to accelerate the biodegradation of Fe-C composite scaffold prepared by selective laser melting. On the one hand, Cu induced micro-galvanic corrosion with Fe matrix due to their differences in potentials, accelerating the electron separation from Fe and further the dissolution of Fe matrix. On the other hand, Cu, as a good conductor of electron transfer, reduced the electron transfer impedance and increased the corrosion current density in Fe/C micro-galvanic cells. Consequently, the degradation rate of Fe-C scaffold was increased by 69% from 0.16 mm/y to 0.27 mm/y in the immersion tests. Additionally, the composite scaffold exhibited compression strength of 128 MPa and hardness of 148 HV, respectively. After co-culturing with the composite scaffold, MG-63 cells presented classical fusiform shape and good cell viability, indicating favorable biocompatibility. These results showed the potential applications of the developed redox systems as highly efficient initiator in accelerating the biodegradation of Fe-based biocomposites.

Stress-Induced Dual-Phase Structure to Accelerate Degradation of the Fe Implant.

Fe is considered as a potential candidate for implant materials, but its application is impeded by the low degradation rate. Herein, a dual-phase Fe30Mn6Si alloy was prepared by mechanical alloying (MA). During MA, the motion of dislocations driven by the impact stress promoted the solid solution of Mn in Fe, which transformed α-ferrite into γ-austenite since Mn was an austenite-stabilizing element. Meanwhile, the incorporation of Si decreased the stacking fault energy inside austenite grains, which tangled dislocations into stacking faults and acted as nucleation sites for ε-martensite. Resultantly, Fe30Mn6Si powder had a dual-phase structure composed of 53% γ-austenite and 47% ε-martensite. Afterward, the powders were prepared into implants by selective laser melting. The Fe30Mn6Si alloy had a more negative corrosion potential of -0.76 ± 0.09 V and a higher corrosion current of 30.61 ± 0.41 µA/cm2 than Fe and Fe30Mn. Besides, the long-term weight loss tests also proved that Fe30Mn6Si had the optimal degradation rate (0.25 ± 0.02 mm/year).

Construction of a stereocomplex between poly(D-lactide) grafted hydroxyapatite and poly(L-lactide): toward a bioactive composite scaffold with enhanced interfacial bonding.

The poly(L-lactide) (PLLA)/hydroxyapatite (HAP) composite scaffold is expected to combine the favorable compatibility and processability of PLLA with the excellent bioactivity and osteoconductivity of HAP. Unfortunately, the poor interfacial bonding between PLLA and HAP leads to a deterioration in mechanical properties. In this study, poly(D-lactide) (PDLA) was grafted onto the surface of HAP nanoparticles (g-HAP), and then g-HAP was incorporated into PLLA to improve interfacial bonding by stereocomplexation in a scaffold fabricated via selective laser sintering (SLS). The results showed that HAP nanoparticles were grafted with PDLA at a grafting rate of 8.72% by ring-opening polymerization through chemical bonding in the presence of the hydroxyl groups of HAP. The grafted PDLA formed an interfacial stereocomplex with PLLA via an intertwined spiral structure ascribed to their antiparallel and complementary configuration under the action of hydrogen bonding. Consequently, the tensile strength and modulus of the PLLA/g-HAP scaffold increased by 86% and 69%, respectively, compared to those of the PLLA/HAP scaffold. In addition, the scaffold displayed good bioactivity by inducing apatite nucleation and deposition and possessed good cytocompatibility for cell adhesion, growth and proliferation.

Synthesis of a mace-like cellulose nanocrystal@Ag nanosystem via in-situ growth for antibacterial activities of poly-L-lactide scaffold.

Antibacterial property for scaffolds is an urgent problem to prevent infections in bone repair. Ag nanoparticles possess excellent bactericidal activities, whereas their agglomeration restricts the full play of antibacterial property in scaffold. Herein, a mace-like nanosystem was constructed to improve their dispersion by in-situ growth of Ag nanoparticles on cellulose nanocrystal (CNC), which was labeled CNC@Ag nanosystem. Subsequently, the CNC@Ag nanosystem was introduced into poly-L-lactide (PLLA) scaffolds. Results demonstrated that the nanosystem uniformly dispersed in scaffold. The antibacterial tests demonstrated that the scaffolds possessed robust antibacterial activities against E. coli, with bacterial inhibition rate over 95%. Moreover, ion release behavior corroborated the scaffolds continuously released Ag+ for more than 28 days, which benefited from the immobilization effect of CNC on Ag. Encouragingly, the mechanical properties of the scaffolds were remarkably higher than that of PLLA/CNC scaffolds, owing to the mace-like CNC@Ag nanosystem improved the load transfer efficiency in the scaffold.

Constructing core-shell structured BaTiO3@carbon boosts piezoelectric activity and cell response of polymer scaffolds.

Piezoelectric composites have shown great potential in constructing electrical microenvironment for bone healing since their integration of polymer flexibility and ceramic piezoelectric coefficient. Herein, core-shell structured BaTiO3@carbon (BT@C) hybrid nanoparticles were prepared by in situ oxidative self-polymerization and template carbonization. Then the BT@C was introduced into polyvinylidene fluoride (PVDF) scaffolds manufactured by selective laser sintering. On one hand, the carbon shell could strengthen the local electric field loaded on BT in poling process owing to it served as a diffusion layer to provide space for charge transfer and accumulation. In this case, more electric domain within BT would be aligned along the polarization field direction and thus promoted the paly of BT's piezoelectric activity. On the other hand, the carbon shell could induce the formation of ß phase due to the sp2 hybrid-bonded carbon atoms in carbon shell forming electrostatic interaction with hydrogen atoms in PVDF chains, which further enhanced the piezoelectric response of the scaffolds. Results showed that the scaffold presented augmented piezoelectric performance with output voltage of 5.7 V and current of 79.8 nA. The improved electrical signals effectively accelerated cell proliferation and differentiation. Furthermore, the scaffold displayed improved mechanical performance due to rigid particle strengthen effect.

Rod-like Eutectic Structure in Biodegradable Zn-Al-Sn Alloy Exhibiting Enhanced Mechanical Strength.

Zn alloy is recognized as a promising biodegradable metal for bone implant applications because of its good biocompatibility and moderate degradation rate. Nevertheless, the insufficient strength limits its applications. In this study, a rod-like eutectic structure was fabricated in Zn-Al-Sn alloy with the addition of Sn via selective laser melting. It was found that the Al-enriched phase nucleated primarily during cooling and caused the rapid precipitation of Zn. This inevitably consumed the liquid Zn and increased the ratio of Sn to Zn in the liquid phase, resulting in the formation of the eutectic, which was composed of the Sn-enriched phase and the Zn-enriched phase. More importantly, the coupled growth of the Sn-enriched and Zn-enriched phases and their volume differences together led to a rod-like morphology of the eutectic according to the volume fraction theory. Consequently, the yield and ultimate compressive strengths were enhanced to 180 ± 18.8 and 325 ± 29.6 MPa for the Zn-Al-2Sn alloy, respectively. This could be attributed to the pinning effect of the rod-like eutectic, which could block dislocation motion and result in dislocation pile-up, thereby conducing to the mechanical reinforcement. In addition, the Zn-Al-Sn alloy also exhibited good biocompatibility and increased degradation rate because of the enhanced galvanic corrosion. This study showed the potential of rod-like eutectic for the mechanical enhancement of the biodegradable Zn alloy.

Interfacial reinforcement in bioceramic/biopolymer composite bone scaffold: The role of coupling agent.

The combination of biopolymer and bioceramic can mimic the chemical composition of the native bone extracellular matrix which is composed of inorganic minerals and organic collagenous. However, the poor interfacial compatibility between organic biopolymer and inorganic bioceramic restricts the full development of bioceramic/biopolymer composite scaffold for bone regeneration application. Coupling agents have been widely used to build a "molecular bridge" in the interface between biopolymer and bioceramic due to the two different functional groups in its structure. One is organophilic functional groups which can react with polymer molecules, and the other is special functional groups which can adsorb on bioceramic surface to form a firm bond. As a result, the stress transfer efficiency between biopolymer and bioceramic can be enhanced, and thereby improving the mechanical properties of the composite scaffold. In this study, the interfacial features between bioceramic and biopolymer and the methods to improve interface bonding were presented, and the interfacial reaction mechanisms under the action of coupling agents especially silane coupling agents were focused on discussing. In addition, the mechanical properties, in vitro and in vivo biological properties of the bioceramic/biopolymer composite scaffold after coupling agent modification were systematically summarized. Finally, suggestions for further work were put forward, including the study on controlling coupling agent content, and more in vitro and in vivo experimental evaluation.

TiO2-Induced In Situ Reaction in Graphene Oxide-Reinforced AZ61 Biocomposites to Enhance the Interfacial Bonding.

Graphene oxide (GO) can improve the degradation resistance of biomedical Mg alloy because of its excellent impermeability and outstanding chemical inertness. However, the weak interfacial bonding between GO and Mg matrix leads to easily detaching during degradation. In this study, in situ reaction induced by TiO2 took place in the AZ61-GO biocomposite to enhance the interfacial bonding between GO and Mg matrix. For the specific process, TiO2 was uniformly and tightly deposited onto the GO surface by hydrothermal reaction (TiO2/GO) first and then used for fabricating AZ61-TiO2/GO biocomposites by selective laser melting (SLM). Results showed that TiO2 was in situ reduced by magnesiothermic reaction during SLM process, and the reduzate Ti, on the one hand, reacted with Al in the AZ61 matrix to form TiAl2 and, on the other hand, reacted with GO to form TiC at the AZ61-GO interface. Owing to the enhanced interfacial bonding, the AZ61-TiO2/GO biocomposite showed 12.5% decrease in degradation rate and 10.1% increase in compressive strength as compared with the AZ61-GO biocomposite. Moreover, the AZ61-TiO2/GO biocomposite also showed good cytocompatibility because of the slowed degradation. These findings may provide guidance for the interfacial enhancement in GO/metal composites for biomedical applications.

Graphene-assisted barium titanate improves piezoelectric performance of biopolymer scaffold.

Biopolymer scaffold is expected to generate electrical stimulation, aiming to mimic an electrical microenvironment to promote cell growth. In this work, graphene and barium titanate (BT) was introduced into selective laser sintered poly-l-lactic acid (PLLA) scaffold. BT as one piezoelectric ceramic was used as the piezoelectric source, whereas graphene served as superior conductive filler. Significantly, the incorporated graphene enhanced the electrical conductivity and thereby increased the electric field strength applied on BT nanoparticles during poling. In this case, more electric domain within BT rearranged along the poling field direction, thus promoting the piezoelectric response of the composites. Results showed that the PLLA/BT/graphene scaffold exhibited relatively high output voltage of 1.4 V and current of 10 nA. Cells tests proved that these electrical signals considerably promoted cell proliferation and differentiation. Moreover, the scaffold exhibited improved mechanical properties due to the rigid particle enhancement effect and increased crystallinity.

In Situ Generation of Hydroxyapatite on Biopolymer Particles for Fabrication of Bone Scaffolds Owning Bioactivity.

Hydroxyapatite (HAP) can endow a biopolymer scaffold with good bioactivity and osteoconductive ability, while the interfacial bonding is fairly weak between HAP and biopolymers. In this study, HAP was in situ generated on poly(l-lactic acid) (PLLA) particles, and then they were used to fabricate a scaffold by selective laser sintering. Detailedly, PLLA particles were first functionalized by dopamine oxide polymerization, which introduced abundance active catechol groups on the particle surface, and subsequently, the catechol groups concentrated Ca2+ ions by chelation in a simulated body fluid solution, and then, Ca2+ ions absorbed PO43- ions through electrostatic interactions for in situ nucleation of HAP. The results indicated that HAP was homogeneously generated on the PLLA particle surface, and HAP and PLLA exhibited good interfacial bonding in the HAP/PLLA scaffolds. Meanwhile, the scaffolds displayed excellent bioactivity by inducing apatite precipitation and provided a good environment for human bone mesenchymal stem cell attachment, proliferation, and osteogenic differentiation. More importantly, the ingrowth of blood vessel and the formation of new bone could be stimulated by the scaffolds in vivo, and the bone volume fraction and bone mineral density increased by 44.44 and 41.73% compared with the pure PLLA scaffolds, respectively. Serum biochemical indexes fell within the normal range, which indicated that there was no harmful effect on the normal functioning of the body after implanting the scaffold.

Surface modification enhances interfacial bonding in PLLA/MgO bone scaffold.

The poor interfacial bonding and resultant agglomeration of nanoparticles in polymer-based composite severely deteriorated their reinforcement effect. In this work, MgO nanoparticles (MgO-NPs) were surface modified with Poly (L-lactic acid-co-malic acid) (PLMA) to improve the interfacial compatibility in Poly-l-lactic acid (PLLA) scaffold manufactured by selective laser sintering. PLMA possess a hydrophilic end with carboxyl group (comes from the malic acid) and an l-lactic acid chain. On one hand, the carboxyl group was able to form hydrogen bonding with the hydroxyl groups of MgO-NPs. On the other hand, the l-lactic acid chain containing the hydroxyl groups could react with the carboxyl group of PLLA. Results revealed that the scaffold exhibited significantly enhanced compressive strength and modulus by 47.1% and 237.7%, respectively, which could be ascribed to the enhanced interfacial bonding between PLLA and MgO-NPs, as well as the rigid particle reinforcement. In addition, the scaffold was favorable for cell adhesion, proliferation and differentiation, owing to the improved hydrophilic and suitable pH environment. It was suggested the scaffold was a promising material for bone repair application.

Functionalized BaTiO3 enhances piezoelectric effect towards cell response of bone scaffold.

Piezoelectric effect of polyvinylidene fluoride (PVDF) plays a crucial role in restoring the endogenous electrical microenvironment of bone tissue, whereas more ß phase in PVDF leads to higher piezoelectric performance. Nanoparticles can induce the nucleation of the ß phase. However, they are prone to aggregate in PVDF matrix, resulting in weakened nucleation ability of ß phase. In this work, the hydroxylated BaTiO3 nanoparticles were functionalized with polydopamine to promote their dispersion in PVDF scaffolds fabricated via selective laser sintering. On one hand, the catechol groups of polydopamine could form hydrogen bonding with the hydroxyl groups of the BaTiO3. On the other hand, the amino groups of polydopamine were able to bond with CF group of PVDF. As a result, the functionalized BaTiO3 nanoparticles homogeneously distributed in PVDF matrix, which significantly increased the ß phase fraction from 46% to 59% with an enhanced output voltage by 356%. Cell testing confirmed the enhanced surface electric cues significantly promoted cell adhesion, proliferation and differentiation. Furthermore, the scaffolds exhibited enhanced tensile strength and modulus, which was ascribed to the rigid particle strengthening effect and the improved interfacial adhesion. This study suggested that the piezoelectric scaffolds shown a potential application in bone repair.