Search

It is of great challenges to repair bone defect and prevent tumor recurrence in bone tumors postoperative treatment. Bone scaffolds loaded with zoledronate (ZOL) are expected to solve these issues due to its osteogenesis and anti-tumor ability. Furthermore, ZOL needs to be sustained release to meet the requirement of long-term therapy. In this study, ZOL was loaded into amination functionalized mesoporous silicon (SBA15NH

Background: Fe3O4 nanoparticles are highly desired for constructing endogenous magnetic microenvironment in scaffold to accelerate bone regeneration due to their superior magnetism. However, their random arrangement easily leads to mutual consumption of magnetic poles, thereby weakening the magnetic stimulation effect. Methods: In this study, magnetic nanochains are synthesized by magnetic-field-guided interface co-assembly of Fe3O4 nanoparticles. In detail, multiple Fe3O4 nanoparticles are aligned along the direction of magnetic force lines and are connected in series to form nanochain structures under an external magnetic field. Subsequently, the nanochain structures are covered and fixed by depositing a thin layer of silica (SiO2), and consequently forming linear magnetic nanochains (Fe3O4@SiO2). The Fe3O4@SiO2 nanochains are then incorporated into poly l-lactic acid (PLLA) scaffold prepared by selective laser sintering technology.Results: The results show that the Fe3O4@SiO2 nanochains with unique core-shell structure are successfully constructed. Meanwhile, the orderly assembly of nanoparticles in the Fe3O4@SiO2 nanochains enable to form magnetic energy coupling and obtain a highly magnetic micro-field. The in vitro tests indicate that the PLLA/Fe3O4@SiO2 scaffolds exhibit superior capacity in enhancing cell activity, improving osteogenesis-related gene expressions, and inducing cell mineralization compared with PLLA and PLLA/Fe3O4 scaffolds. Conclusion: In short, the Fe3O4@SiO2 nanochains endow scaffolds with good magnetism and cytocompatibility, which have great potential in accelerating bone repair.

Background Fe3O4 nanoparticles are highly desired for constructing endogenous magnetic microenvironment in scaffold to accelerate bone regeneration due to their superior magnetism. However, their random arrangement easily leads to mutual consumption of magnetic poles, thereby weakening the magnetic stimulation effect. Methods In this study, magnetic nanochains are synthesized by magnetic-field-guided interface co-assembly of Fe3O4 nanoparticles. In detail, multiple Fe3O4 nanoparticles are aligned along the direction of magnetic force lines and are connected in series to form nanochain structures under an external magnetic field. Subsequently, the nanochain structures are covered and fixed by depositing a thin layer of silica (SiO2), and consequently forming linear magnetic nanochains (Fe3O4@SiO2). The Fe3O4@SiO2 nanochains are then incorporated into poly l-lactic acid (PLLA) scaffold prepared by selective laser sintering technology. Results The results show that the Fe3O4@SiO2 nanochains with unique core–shell structure are successfully constructed. Meanwhile, the orderly assembly of nanoparticles in the Fe3O4@SiO2 nanochains enable to form magnetic energy coupling and obtain a highly magnetic micro-field. The in vitro tests indicate that the PLLA/Fe3O4@SiO2 scaffolds exhibit superior capacity in enhancing cell activity, improving osteogenesis-related gene expressions, and inducing cell mineralization compared with PLLA and PLLA/Fe3O4 scaffolds. Conclusion In short, the Fe3O4@SiO2 nanochains endow scaffolds with good magnetism and cytocompatibility, which have great potential in accelerating bone repair.

Black phosphorus (BP) exhibits great potential as antibacterial materials due to its unique photocatalytic activity. However, the unsatisfactory optical absorption and quick recombination of photoinduced electron–hole pairs restrain its photocatalytic antibacterial performance. In this work, silver nanoparticles (AgNPs) were decorated on BP to construct BP@AgNPs nanohybrids and then introduced into poly-l-lactic acid scaffold. Combining the tunable bandgap of BP and the LSPR effect of AgNPs, BP@AgNPs nanohybrids displayed the broaden visible light absorption. Furthermore, AgNPs acted as electron acceptors could accelerate charge transfer and suppress electron–hole recombination. Therefore, BP@AgNPs nanohybrids achieved synergistically enhanced photocatalytic antibacterial activity under visible light irradiation. Fluorescence probe experiment verified that BP@AgNPs promoted the generation of reactive oxygen species, which could disrupt bacteria membrane, damage DNA and oxide proteins, and finally lead to bacteria apoptosis. As a result, the scaffold possessed strong antibacterial efficiency with a bactericidal rate of 97% under light irradiation. Moreover, the scaffold also exhibited good cytocompatibility. This work highlighted a new strategy to develop photocatalytic antibacterial scaffold for bone implant application.

Black phosphorous (BP) is recognized as an effective reinforcement for polymer scaffold because of its excellent mechanical property and biocompatibility. Nevertheless, its poor stability in physiological environment limits its application in bone repair. In this work, BP was modified with dopamine by self-polymerization approach (donated as BP@PDA) to improve its stability, and then was introduced into poly-L-lactic acid (PLLA) scaffold fabricated by selective laser sintering technology. Results showed the compressive and tensile strength of PLLA/BP@PDA scaffold were improved by 105% and 50%, respectively. The enhanced strength was ascribed to the increased stability of BP and the improved compatibility of BP@PDA with PLLA matrix after modifying with polydopamine. Simultaneously, the bioactivity of PLLA scaffold was significantly improved. It was attributed to that BP@PDA provided the sustained source of PO43- ions which could capture Ca2+ ions from physiological medium to facilitate in situ biomineralization, thereby promoting cell adhesion, proliferation and differentiation. This study demonstrated the great potential of BP@PDA in bone repair.

Poly-L-lactic acid (PLLA) lacks osteogenic activity, which limits its application in bone repair. Zinc (Zn) is widely applied to strengthen the biological properties of polymers due to its excellent osteogenic activity. In the present study, Zn-doped mesoporous silica (Zn-MS) particles were synthesized by one-pot hydrothermal method. Then, the particles were induced into PLLA scaffolds prepared by selective laser sintering technique, aiming to improve their osteogenic activity. Our results showed that the synthesized particles possessed rosette-like morphology and uniform mesoporous structure, and the composite scaffold displayed the sustained release of Zn ion in a low concentration range, which was attributed to the shield effect of the PLLA matrix and the strong bonding interaction of Si-O-Zn. The scaffold could evidently promote osteogenesisdifferentiation of mouse bone marrow mesenchymal stem cells by upregulating their osteogenesis-related gene expression. Besides, Zn-MS particles could significantly increase the compressive strength of the PLLA scaffold because of their rosettelike morphology and mesoporous structure, which can form micromechanical interlocking with the PLLA matrix. The Zn-MS particles possess great potential to improve various polymer scaffold properties due to their advantageous morphology andphysicochemical properties.

Anti-washout calcium phosphate cement (CPC) was prepared by dissolving water-soluble konjac glucomannan (KGM) and κ-carrageenan (KC) blend in the cement liquid. The anti-washout property, setting time, compressive strength and in vitro cytocompatibility of the CPC modified with KGM/KC blend were evaluated. The results indicated that the CPC pastes modified with KGM/KC blend exhibited excellent anti-washout property. The addition of KGM/KC blend shortened the setting time and increased the injectability of CPC. Although the introduction of KGM/KC blend reduced the compressive strength of CPC, the compressive strength still surpassed that of human cancellous bone. The optimal KGM/KC mass ratio was 2:8, with which the modified cement exhibited the most efficient washout resistance and the highest compressive strength. The introduction of KGM/KC blend obviously promoted the proliferation of mouse bone marrow mesenchymal stem cells. This anti-washout CPC modified by KGM/KC blend with excellent in vitro cytocompatibility will have good prospects for application in bone defect repair.

Reduced graphene oxide (RGO) shows great advantages as nano reinforcement for zinc (Zn) based implants owing to its excellent fracture strength, large specific surface area and good biocompatibility. Nevertheless, the poor interfacial bonding between Zn matrix and RGO impairs the strengthening efficiency. In this work, titanium carbide (TiC) was used as an interface bridging between Zn matrix and RGO to improve the interface adhesion. On one hand, TiC was in-situ generated on RGO plane through chemical vapor deposition, and tightly integrated together via chemical bond. On the other hand, a semi-coherent bonding was formed between TiC and Zn matrix, owing to the small lattice misfit and similar atomic arrangement between the (200)Zn plane and (002)TiC plane. Results showed that TiC@RGO offered an improved strengthening efficiency with tensile strength of scaffolds increasing from 30.6 to 59.9 MPa, as the TiC nanoparticles considerably enhanced the load transfer strengthening of RGO and contributed an Orowan strengthening. Significantly, it also improved the plasticity of Zn scaffolds, since the semi-coherent structure inhibited the premature stress concentration and dislocation accumulation. Moreover, TiC@RGO promoted the cell differentiation behavior of Zn scaffolds.

Implant-related bacterial infection is a serious complication, which even causes implant failure. Silver (Ag) nanoparticles are broadly used antibacterial agents due to their excellent antibacterial ability and broad-spectrum bactericidal property. However, the significance of burst release cannot be entirely ignored. In this study, Ag doped mesoporous bioactive glasses (Ag-MBG) nanospheres were synthesized using modified Stober method, then incorporated into poly L-lactic acid (PLLA) matrix to prepare the composite scaffolds via selective laser sintering (SLS) technology. Herein, Mesoporous bioactive glasses (MBG) sol had many negatively-charged silicon hydroxyl groups, which could adsorb positively-charged Ag ions by electrostatic interaction and eventually form Si-O-Ag bonds into MBG. Moreover, MBG promoted osteoblast colonization due to its continuous release of Si ions. The results showed the Ag-MBG/PLLA scaffold could sustainedly release Ag ions for 28 days, and exhibited significantly antibacterial ability against Escherichia coli, its bacterial inhibition rate was over 80%. In addition, the composite scaffold also showed good cytocompatibility. It may be concluded that the prepared Ag-MBG/PLLA scaffold has great potential to repair implant-associated bone infection.

Ceramic-metal composite materials, namely cermets, are provided with characteristics of both ceramic and metal. Herein, for the first time bio-cermets based on β-tricalcium phosphate (β-TCP) bioceramic with biodegradable iron being reinforcement phase, were fabricated using the powder metallurgic method. The phase composition, microstructure, mechanical properties and in vitro cell behaviors of bio-cermets were investigated. The results revealed that atomic diffusion occurred between the iron and β-TCP matrix during the sintering process. The bio-cermets attained remarkable increase in fracture toughness (1.16–1.55 MPa m1/2) compared to the β-TCP bioceramic (0.54 MPa m1/2). The bio-cermets with 10 vol% iron showed the highest compressive strength (640 MPa), significantly higher than that of plain β-TCP bioceramic (285 MPa). The in vitro cell behaviors test indicated that the bio-cermets did not showed any sign of toxicity; the iron ions released from bio-cermets up-regulated bone-related gene expression of bone mesenchymal stem cells. The bio-cermets developed in this study represent potential bone substitutes for application in the load-bearing bone defects.

Scaffold of gelatin-chondroitin sulfate-hyaluronan-polyvinyl alcohol (GCH-PVA) with orientated microtubule structure and good hydrophilicity was fabricated by unidirectional freeze-drying method mimicking the composition and structure of tracheal cartilage extracellular matrix. PVA was incorporated to improve flexibility and viscoelasticity of GCH scaffold. All wet scaffolds showed similar compressive elastic modulus with native cartilage. GCH-PVA scaffolds showed high relative remaining stress during relaxation indicating good mechanical stability. The hysteresis ratio during cyclic compression increased gradually with PVA content and close to native cartilage. During multiple frequency compression, all scaffolds showed a low loss tangent close to native cartilage, and PVA incorporation enhanced the elasticity of scaffolds when they were stressed under high frequency. The incorporation of PVA promoted gene expression of adhesion related integrin α5β1 and actin by mouse bone marrow mesenchymal stem cells (mBMSCs). With the orientated microtubule structure, cells ingrowth into scaffolds was facilitated by dynamic culture method.

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.

Fe has attracted great attention as biodegradable bone implant. Unfortunately, its degradation rate is too slow for bone repair. It is well known that the lower the electrode potential is, the faster the metals degrade. In the case of dissolving low electrode potential species (Mg for instance) into Fe lattice, the corrosion potential of the matrix can be negatively shifted and the overall degradation rate can be accelerated. However, Fe and Mg are immiscible in equilibrium due to their large differences in melting and boiling temperature. In this study, a supersaturated Fe–Mg solid solution was developed in solid-state by mechanical alloying (MA). In detail, Fe particles experienced cycled mechanical impact and friction during MA, which produced a large number of dislocations and defects. In this condition, Mg atoms were forcibly diffused into Fe lattice along with the motion of dislocations and defects. The results showed that about 8.5 at.% Mg was dissolved in Fe (0.02 at.% in equilibrium). Subsequently, the MA powders were fabricated into bone implants by selective laser melting (SLM), in which the fast laser scanning speed resulted in a rapid cooling rate. The molten liquid passed the immiscible zone quickly, thereby avoiding the separation of Mg solute. SLMed implants exhibited a lowered electrode potential (−0.93 V) comparing with Fe. Additionally, the implants also had good cytocompatibility and promoted cell proliferation.

Poly l-lactic acid (PLLA) was limited in the further orthopaedic application due to its insufficient mechanical property and poor bioactivity. Graphene oxide (GO) is an effective reinforcement, whereas silicon-doped hydroxyapatite (Si-HA) possesses excellent bioactivity, but either GO or Si-HA tends to aggregate in PLLA matrix. In this study, a GO@Si-HA nanosystem was achieved by in-situ growth of Si-HA on GO, and then incorporated into PLLA scaffold fabricated by laser sintering technology. On one hand, Si-HA on the surface of GO effectively prevented the aggregation of GO by acting as a barrier between GO nanosheets. On the other hand, GO hindered the aggregation of Si-HA by means of anchoring Si-HA. Results displayed that the compressive strength and modulus of the PLLA/GO@Si-HA composite scaffold were enhanced by 85% and 120%, respectively. Meanwhile, the scaffold exhibited significantly improved bioactivity, and consequently promoted cell adhesion, proliferation and differentiation. The developed PLLA/GO@Si-HA composite scaffold with excellent mechanical properties and superior bioactivity could serve as a promising substitute for bone repairing.

Polyvinylidene fluoride (PVDF)/barium titanate (BaTiO3) composites are becoming increasingly attractive in bone repair since it combines the advantage of polymer flexibility and ceramic piezoelectric constant. Herein, silver (Ag) nanoparticles were decorated on polydopamine functioned BaTiO3 (Ag-pBT) by in situ growth. Then the strawberry-like structured Ag-pBT nanoparticles were introduced into PVDF scaffold fabricated by selective laser sintering. On one hand, Ag nanoparticles would act as a conductive phase to enhance the strength of the polarized electric field on BaTiO3, thereby forcing more domains to be aligned in the direction of the electric field and make piezoelectric effect of BaTiO3 fully play in composite scaffold. On the other hand, Ag nanoparticles would attack multiple targets in bacteria by release of Ag+ and production of reactive oxygen species. In fact, the antibacterial activity is highly desirable for bone repair. Results demonstrated that the PVDF/4Ag-pBT scaffold exhibited enhanced piezoelectric properties with output current and voltage increased by 50% and 40% than that of PVDF/pBT, respectively. In vitro cell culture confirmed that the enhanced electric output further promoted cell proliferation and differentiation. Meanwhile, the scaffold presented robust antibacterial activity against E.coli.

Calcium phosphate cement (CPC) is an excellent bone graft material due to its self-setting, easiness to shape, good biocompatibility and osteoconductivity. However, low osteogenic activity and slow degradation rate of CPC severely influence its bone regeneration efficiency. Herein, zinc silicate (ZS) and poly (lactic-co-glycolic acid) (PLGA) microspheres were incorporated into CPC to overcome these issues. The addition of ZS obviously downregulated the expression of inflammatory-related genes (interleukin-1β, interleukin-6, and tumor necrosis factor α), while markedly upregulated the anti-inflammatory gene expression (interleukin-10). The incorporation of ZS significantly promoted the adhesion and proliferation of mouse bone marrow stem cells (mBMSCs). In addition, macrophage-conditioned ZS/PLGA/CPC extracts profoundly promoted osteogenic differentiation of mBMSCs, and evidently suppressed osteoclastogenesis of RAW264.7 cells. The optimum added amount of ZS was 10 wt.%. In vivo results also displayed that the addition of 10 wt.% ZS significantly improved bone repair effect of the composite. Therefore, the addition of ZS together with PLGA microspheres is a promising way for modifying the osteogenic activity and degradability of CPC via in-situ pore generation, promoting osteogenic differentiation and macrophage immunomodulation due to the simultaneous release of active silicon and zinc ions.

Inefficient bone regeneration of self-hardening calcium phosphate cement (CPC) increases the demand for interconnected macropores and osteogenesis-stimulated substances. It remains a challenge to fabricate porous CPC with interconnected macropores while maintaining its advantages, such as plasticity. Herein, pastes containing CPC and wollastonite (WS) are infiltrated into a 3D plotted poly(lactic-co-glycolic acid) (PLGA) network to fabricate plastic CPC-based composite cement (PLGA/WS/CPC). The PLGA/WS/CPC recovers the plasticity of CPC after being heated above the glass transition temperature of PLGA. The presence of the 3D PLGA network significantly increases the flexibility of CPC in prophase and generates 3D interconnected macropores in situ upon its degradation. The addition of WS is helpful to improve the attachment, proliferation, and osteogenic differentiation of mouse bone marrow stromal cells in vitro. The in vivo experimental results indicate that PLGA/WS/CPC promotes rapid angiogenesis and bone formation. Therefore, the plastic CPC-based composite cement with a 3D PLGA network and wollastonite shows an obviously improved efficiency for repairing bone defects and is expected to facilitate the wider application of CPC in the clinic.

Polymer sphere-based scaffolds, which are prepared by bonding the adjacent spheres via sintering the randomly packed spheres, feature uniform pore structure, full three-dimensional (3D) interconnection, and considerable mechanical strength. However, bioceramic sphere-based scaffolds fabricated by this method have never been reported. Due to high melting temperature of bioceramic, only limited diffusion rate can be achieved when sintering the bioceramic spheres, which is far from enough to form robust bonding between spheres. In the present study, for the first time we fabricated 3D interconnected β-tricalcium phosphate ceramic sphere-based (PG/TCP) scaffolds by introducing phosphate-based glass (PG) as sintering additive and placing uniaxial pressure during the sintering process. The sintering mechanism of PG/TCP scaffolds was unveiled. The PG/TCP scaffolds had hierarchical pore structure, which was composed by interconnected macropores (>200 μm) among spheres, pores (20–120 μm) in the interior of spheres, and micropores (1–3 μm) among the grains. During the sintering process, partial PG reacted with β-TCP, forming β-Ca2P2O7; metal ions from PG substituted to Ca2+ sites of β-TCP. The mechanical properties (compressive strength 2.8–10.6 MPa; compressive modulus 190–620 MPa) and porosity (30%–50%) of scaffolds could be tailored by manipulating the sintering temperatures. The introduction of PG accelerated in vitro degradation of scaffolds, and the PG/TCP scaffolds showed good cytocompatibility. This work may offer a new strategy to prepare bioceramic scaffolds with satisfactory physicochemical properties for application in bone regeneration.