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The construction of the nanohybrid composed of two carbonaceous nanomaterials is a promising strategy to inhibit their aggregation, and effectively exert the advantages of their excellent mechanical properties as reinforcement for polymers. Here, carbon nanotubes (CNTs) were in situ perpendicularly growing on the surface of graphene oxide (GO) through metal-organic frameworks (MOF)-derived strategy by chemical vapor deposition (CVD), aiming to facilitate their dispersion on poly(l-lactic acid) (PLLA) bone scaffold fabricated by selective laser sintering (SLS). Specifically, GO provided nucleation sites for the growth of MOF, and worked as the templates when CNTs grew, in which MOF provided catalysts and carbon sources simultaneously. The precursor was heated to 550 °C and kept for 2 h, then heated to 900 °C and kept for 2 h before cooling. The obtained nanohybrid (GO@CNT) exhibited a superior dispersion state than the pure GO in the scaffold at the same loading, especially when the loading was 0.75 wt%. Adding 0.75 wt% GO@CNT endowed the scaffold with a remarkable increment in tensile strength and compressive strength of 13.36 MPa and 24.72 MPa with enhancement of 55.35% and 18.85%, respectively, compared to the scaffold containing 0.75 wt% GO. A crack extension model combined with experiment results was proposed to better understand reinforcement mechanisms. Additionally, the scaffold containing GO@CNT exhibited benign cytocompatibility with a cell-spreading area of 86.31% and cell density of 564 cells/mm2 after culturing for 5 d according to the results of cell adhesion and immunofluorescence tests, making it a promising candidate for bone defect repair.

ABSTRACTCombining poly (L-lactic acid) (PLLA) with thermoplastic polyurethane elastomer (TPU) can integrate the advantages of excellent biocompatibility and intrinsic shape memory ability of PLLA and high elasticity and excellent shape memory properties of TPU in the application of minimally invasive surgery for bone tissue engineering. However, TPU easily forms a sea-island-like structure in PLLA matrix, decreasing shape memory properties. In this study, a co-continuous structure of TPU phase in PLLA matrix was constructed by adding Fe3O4 nanoparticles due to the changed interfacial tension and flow behavior of TPU, which endowed the TPU/PLLA/Fe3O4 blend fabricated via selective laser sintering (SLS) with excellent shape memory properties. As a result, the morphology of TPU in the blend changed from sea-island-like structure to complete co-continuous structure with increasing Fe3O4 content (0 to 10wt%), and shape recovery ratios in 50 °C water increased from 66.67 to 95.92%. The introduction of Fe3O4 endowed the blend with magnetic responsive shape memory in alternating magnetic field because Fe3O4 could heat it by generating heat from relative friction and particle collisions. Besides, the tensile modulus and hardness of the specimen with 10wt% Fe3O4 nanoparticles increased. In addition, the blend demonstrated excellent biocompatibility by promoting cell adhesion, spreading, and proliferation.

Introduction: Scaffolds loaded with antibacterial agents and osteogenic drugs are considered essential tools for repairing bone defects caused by osteomyelitis. However, the simultaneous release of two drugs leads to premature osteogenesis and subsequent sequestrum formation in the pathological situation of unthorough antibiosis. Objectives: In this study, a spatiotemporal drug-release polydopamine-functionalized mesoporous silicon nanoparticle (MSN) core/shell drug delivery system loaded with antibacterial silver (Ag) nanoparticles and osteogenic dexamethasone (Dex) was constructed and introduced into a poly-l-lactic acid (PLLA) scaffold for osteomyelitis therapy. Methods: MSNs formed the inner core and were loaded with Dex through electrostatic adsorption (MSNs@Dex), and then polydopamine was used to seal the core through the self-assembly of dopamine as the outer shell (pMSNs@Dex). Ag nanoparticles were embedded in the polydopamine shell via an in situ growth technique. Finally, the Ag-pMSNs@Dex nanoparticles were introduced into PLLA scaffolds (Ag-pMSNs@Dex/PLLA) constructed by selective laser sintering (SLS). Results: The Ag-pMSNs@Dex/PLLA scaffold released Ag+ at the 12th hour, followed by the release of Dex starting on the fifth day. The experiments verified that the scaffold had excellent antibacterial performance against Escherichia coli and Staphylococcus aureus. Moreover, the scaffold significantly enhanced the osteogenic differentiation of mouse bone marrow mesenchymal stem cells. Conclusion: The findings suggested that this spatiotemporal drug release scaffold had promising potential for osteomyelitis therapy.

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.

Biodegradable magnesium (Mg) and its alloy show huge potential as temporary bone substitute due to the favorable biocompatibility and mechanical compatibility. However, one issue deserves attention is the too fast degradation. In this work, mesoporous bioglass (MBG) with high pore volume (0.59 cc/g) and huge specific surface area (110.78 m2/g) was synthesized using improved sol-gel method, and introduced into Mg-based composite via laser additive manufacturing. Immersion tests showed that the incorporated MBG served as powerful adsorption sites, which promoted the in-situ deposition of apatite by successively adsorbing Ca2+ and HPO42−. Such dense apatite film acted as an efficient protection layer and enhanced the corrosion resistance of Mg matrix, which was proved by the electrochemical impedance spectroscopy measurements. Thereby, Mg based composite showed a significantly decreased degradation rate of 0.31 mm/year. Furthermore, MBG also improved the mechanical properties as well as cell behavior. This work highlighted the advantages of MBG in the fabrication of Mg-based implant with enhanced overall performance for orthopedic application.

Nasopharyngeal carcinoma (NPC) is a particular type of tumor connected to Epstein-Barr virus infection, genetic, and environmental factors. It is typically discovered late, with few therapeutic options and poor clinical outcomes. Cellular immune responses can be attenuated when programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) are combined. Although PD-1 inhibitors have a different anti-tumor response rate than chemotherapy alone, they can nevertheless considerably outperform chemotherapy in patients with metastatic or recurrent NPC. The nuclear β-catenin can bind to the CD274 promoter region, promoting transcription and upregulating the expression of tumor-specific PD-L1. Separation of β-catenin from E-cadherin and translocation it into nucleus were both aided by β-catenin phosphorylates at the Tyr654 site. Its function in NPC and the expression of PD-L1 have not yet been investigated. This study investigated the predictive significance of PD-L1 and p-β-cateninTyr654 expressions in NPC. Our findings indicated that patients with distant metastases or poor prognoses exhibited higher levels of PD-L1 and p-β-cateninTyr654 expressions. According to Cox multivariate prognostic analysis, PD-L1 was also an effective indicator for predicting the survival status of patients with NPC. We subsequently demonstrated that PD-L1 transcription and protein production could be downregulated by targeting inhibition of the level of β-catenin in NPC cells. This is for developing the β-catenin or TCF4 inhibitor as a potential new option for immune checkpoint immunosuppression in NPC.

Abstract 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.

Carbon nanofibre (CNF) is a potential reinforcement in Zn implants. Nevertheless, its poor interfacial compatibility reduces the reinforcement efficiency drastically. In this study, rare earth lanthanum (La) was used as a compatible interface layer between CNF and Zn matrix. On the one hand, La in situ grew on acidified CNF by a chemical synthesis and achieved a firm coordination covalent bond with the oxygenated functional group derived from CNF. On the other hand, La, as an active rare earth element, could carry out the alloying reaction with the Zn matrix, thus forming strong metal bonding. Results showed that the tensile strength of composites was enhanced from 180.2 ± 12.1 to 243.4 ± 10.2 MPa since the La interface layer promoted the transfer of the interfacial shear stress from the Zn matrix to CNF and thereby consumed massive fracture energy. Encouragingly, it simultaneously improved the ductility, as La activated basal slip and improved the dislocation accommodation capacity. Moreover, the Zn implants displayed excellent anti-tumour efficiency.

Abstract Background The differentiation of human induced pluripotent stem cells (iPSCs) into oocytes, which involves the transformation from mitosis to meiosis, has been a hotspot of biological research for many years and represents a desirable experimental model and potential strategy for treating infertility. At present, studies have shown that most cells stagnate in the oogonium stage after differentiation into primordial germ cells (PGCs) from human iPSCs. Methods iPSCs carrying a SYCP3-mkate2 knock-in reporter were generated by the CRISPR/Cas9 strategy to monitor meiosis status during induced differentiation from iPSCs into oocytes. These induced PGCs/oogonia were activated by small molecules from the Wnt signaling pathway and then cocultured with reconstructed human ovarian nests in vivo for further development. Results First, human PGCs and oogonia were efficiently induced from iPSCs. Second, induced dormant PGCs resumed meiosis and then differentiated into primary oocytes through the in vitro activation of the Wnt signaling pathway. Finally, a new coculture system involving the reconstruction of ovarian nests in vitro could facilitate the differentiation of oocytes. Conclusions Human PGCs/oogonia induced from iPSCs can be activated and used to resume meiosis by molecules of the Wnt signaling pathway. The coculture of activated PGCs and reconstruction of ovarian nests facilitated differentiation into primary oocytes and the generation of haploid human oocytes in vivo. These findings established a new strategy for germline competence in primary oocytes and provided a keystone for human gametogenesis in vitro and in vivo.

Introduction: Nano-SiC has attracted great attention as ceramic reinforcement in metal matrix composites, but the weak interface bonding between them remains a bottleneck for efficient strengthening. Objective: In this study, pre-oxidation treatments and selective laser melting (SLM) were employed to prepare Zn/nano-SiC biocomposites with strengthened interface bonding via in situ reaction. Methods: Nano-SiC and Zn powders were pre-oxidized respectively, and then used to prepare Zn/nano-SiC biocomposites via SLM. The powder microstructure, and the interface characteristics and mechanical properties of the biocomposites were investigated. The degradation properties and cell response were analyzed to evaluate their feasibility for orthopedic applications. Results: The results indicated that the pre-oxidation treatments generated a uniform oxide layer on the surface of both nano-SiC and Zn particles and the thickness of the oxide layer increased with pre-oxidation temperature. During the SLM process, the oxide layers not only improved the metal-ceramic wettability by reducing interface energy, but also induced in situ reaction to form chemical bonding between the Zn matrix and nano-SiC, thereby improving the interface bonding. Consequently, the Zn biocomposite reinforced by nano-SiC with a pre-oxidation temperature of 1000 °C (ZS1000 biocomposite) exhibited more transgranular fracture and significantly enhanced compressive yield strength of 171.5 MPa, which was 31.6% higher than that of the Zn biocomposite reinforced by nano-SiC without pre-oxidation. Moreover, the ZS1000 biocomposite presented slightly accelerated degradation which might be ascribed to the facilitated electron transfer by the interface product (Zn2SiO4). In addition, the ZS1000 biocomposite also showed appropriate biocompatibility for MG-63 cell adhesion, growth, and proliferation. Conclusion: This study shows the potential practical applicability for the preparation of Zn-based biocomposites with strong interface bonding and mechanical properties for orthopedic applications.

The repair of segmental bone defects caused by traumatic injury or pathological diseases remains a substantial challenge in clinic. Poly-l-lactic acid (PLLA) is recognized as one potential bone substitute material due to its natural biodegradability and excellent biocompatibility. Nevertheless, it still faces several fundamental puzzles including insufficient mechanical properties, slow degradation and poor osteogenic activity. To address these issues, the corresponding strategies were thoroughly explored in this review. Regulation of molecular weight and crystallization, as well as the control of crack propagation were the mainstream methods to improve the mechanical properties of PLLA, whereas surface medication and polymer blending was commonly adopted to regulate the degradation behavior. To achieve desirable tissue regeneration ability, the combination of physical stimulation (electric and magnetic) brings about a new and attractive solution, since it is able to mimic the electro-magnetic microenvironment of human body. Furthermore, future research directions are proposed from the prospects of fabrication process, dynamic degradation and multifunctional application. This review aims to offer deep insights and meaningful guidelines for future study of PLLA as implants.

Magnetostrictive alloys have attracted increasing attention in biomedical applications because of the ability to generate reversible deformation in the presence of external magnetic fields. This review focuses on the advances in magnetostrictive alloys and their biomedical applications. The theories of magnetostriction are systematically summarized. The different types of magnetostrictive alloys and their preparation methods are also reviewed in detail. The magnetostrictive strains and phase compositions of typical magnetostrictive alloys, including iron based, rare-earth based and ferrite materials, are presented. Besides, a variety of approaches to preparing rods, blocks and films of magnetostriction materials, as well as the corresponding methods and setups for magnetostriction measurement, are summarized and discussed. Moreover, the interactions between magnetostrictive alloys and cells are analyzed and emphasis is placed on the transduction and transformation process of mechanochemical signals induced by magnetostriction. The latest applications of magnetostrictive alloys in remote microactuators, magnetic field sensors, wireless implantable devices and biodegradable implants are also reviewed. Furthermore, future research directions of magnetostrictive alloys are prospected with focus on their potential applications in remote cell actuation and bone repair.

Abstract Background The reinforcement effect of fiber-reinforced polymer composites is usually limited because of the poor interfacial interaction between fiber and polymer, though fiber reinforcement is regarded as an effective method to enhance the mechanical properties of polymer. Methods In this study, nano-SiO2 particles grafted by 3-Glycidoxypropyltrimethoxysilane (KH560) were introduced onto the surface of 3-Aminopropyltriethoxysilane (KH550) modified carbon fiber (CF) by a self-assembly strategy to improve the interfacial bonding between CF and biopolymer poly (lactic acid) (PLLA). Results The results indicated that PLLA chains preferred to anchor at the surface of nano-SiO2 particles and then formed high order crystalline structures. Subsequently, PLLA spherulites could epitaxially grow on the surface of functionalized CF, forming a transcrystalline structure at the CF/PLLA interface. Meanwhile, the nano-SiO2 particles were fixed in the transcrystalline structure, which induced a stronger mechanical locking effect between CF and PLLA matrix. The results of tensile experiments indicated that the PLLA/CF-SiO2 scaffold with a ratio of CF to SiO2 of 9:3 possessed the optimal strength and modulus of 10.11 MPa and 1.18 GPa, respectively. In addition, in vitro tests including cell adhesion and fluorescence indicated that the scaffold had no toxicity and could provide a suitable microenvironment for the growth and proliferation of cell. Conclusion In short, the PLLA/CF-SiO2 scaffold with good mechanical properties and cytocompatibility had great potential in the application of bone tissue engineering.

The HD-Zip family of transcription factors is unique to the plant kingdom, and play roles in modulation of plant growth and response to environmental stresses. R. glutinosa is an important Chinese medicinal material. Its yield and quality are susceptible to various stresses. The HD-Zip transcription factors is unique to the plant, and roles in modulation of plant growth and response to environmental stresses. However, there is no relevant research on the HD-ZIP of R. glutinosa. In this study, 92 HD-Zip transcription factors were identified in R. glutinosa, and denominated as RgHDZ1-RgHDZ92. Members of RgHDZ were classified into four groups (HD-ZipI-IV) based on the phylogenetic relationship of Arabidopsis HD-Zip proteins, and each group contains 38, 18, 17, and 19 members, respectively. Expression analyses of RgHDZ genes based on transcriptome data showed that the expression of these genes could be induced by the endophytic fungus of R. glutinosa. Additionally, we showed that RgHDZ genes were differentially expressed in response to drought, waterlogging, temperature, and salinity treatments. This study provides important information for different expression patterns of stress-responsive HD-Zip and may contribute to the better understanding of the different responses of plants to biotic and abiotic stresses, and provide a molecular basis for the cultivation of resistant varieties of R. glutinosa.

Polycaprolactone (PCL) has been extensively investigated in the field of bone tissue engineering due to its good biocompatibility, biodegradability and processability. Nevertheless, the lack of bioactivity results in poor osseointegration between artificial implant and host bone tissue, which severely restricts its application for bone regeneration. In this study, PCL powder was first surface functionalized with polydopamine (PDA) coating through oxidative self-polymerization of monomer dopamine, and the PDA modified PCL powder was used for the fabrication of bone scaffold with intrinsic bioactivity via selective laser sintering (SLS). The results suggested that PDA was modified on the PCL powder surface successfully and still remained after laser sintering. The 3D printed scaffold achieved a transition from bioinert to bioactive as evaluated by the formation of apatite on its surface, which was the result of the interaction between the abundant active catechol groups in the introduced PDA and calcium ion from simulated body fluid. Besides, the scaffold provided more hydrophilic surfaces for cell adhesion and growth than the pure PCL scaffold due to the presence of amino and hydroxyl functional group.

Magnetostrictive Fe-Ga alloys have received extensive attention for their good mechanical properties and low saturation magnetization. However, the magnetostriction of bulk polycrystalline Fe-Ga alloys always suffers a major setback due to random grain orientation. In this study, selective laser melting (SLM) was used for the first time to manufacture bulk polycrystalline Fe81Ga19 alloys, and different scanning paths were determined for revealing the influences on grain orientation and magnetostrictive properties. The results showed that elongated columnar grains formed in the building direction due to the epitaxial growth during SLM. For zigzag scanning, grain orientation was parallel to the building direction while tilted by ∼17° for unidirectional scanning. And annular scanning resulted in mixed grain orientations in the alloys. Moreover, Fe81Ga19 alloy with zigzag scanning exhibited 〈100〉 preferred grain orientation. Consequently, the saturated magnetostriction of bulk Fe81Ga19 alloy with zigzag scanning reached ∼77.2 ppm, representing 23.9% and 25.1% increments compared with unidirectional and annular scanning, respectively. The Fe81Ga19 alloy with zigzag scanning also presented an ultimate compressive strength of 448.6 MPa and a degradation rate of 0.09 mm/y, as well as favorable biocompatibility. These results indicated that SLM might be a potential method for manufacturing magnetostrictive bulk Fe-Ga alloys for implant applications.

The incorporation of carbon nanotubes (CNT) and hydroxyapatite (HA) into biopolymer as bone scaffold is expected to combine the excellent mechanical properties of CNT and bioactivity of HA. However, the dispersion of CNT and HA in biopolymer is a challenge. In this paper, under the condition of hydrothermal reaction, HA nanoparticles were in situ synthesized on the surface of carboxyl multi-walled CNT to prevent their aggregation in poly (ε-caprolactone) (PCL) scaffold prepared by selective laser sintering (SLS). The mechanism of in situ synthesis of HA nanoparticles was that the carboxyl functional groups of cCNT acted as anchor sites for Ca2+ deposition, and then Ca2+ attracted HPO42− via electrovalent bonding to in situ nucleation and synthesis of HA nanocrystals. The results demonstrated that HA nanoparticles ranged from about 10 to 30 nm in diameter and 40–80 nm in length were homogeneously generated on the surface of cCNT. Compared with the pure PCL scaffold, the scaffold with contenting of 12% cCNT-HA was increased by 86.6% and 31.9% in tensile and compressive strength, respectively. The strengthening mechanisms could be explained from the bridging and pulling out of the cCNT-HA. Meanwhile, the mineralization experiment results demonstrated that the Ca/P ratio of apatite layer formed on the surface of the PCL/12% cCNT-HA scaffold was 1.66, which was close to that of human bone tissue, indicating the scaffold possessed good bioactivity for inducing the formation of apatite mineralization. Besides, the scaffolds displayed good cytocompatibility for cell attachment, growth and proliferation.

Zinc (Zn) possesses desirable degradability and favorable biocompatibility, thus being recognized as a promising bone implant material. Nevertheless, the insufficient mechanical performance limits its further clinical application. In this study, reduced graphene oxide (RGO) was used as reinforcement in Zn scaffold fabricated via laser additive manufacturing. Results showed that the homogeneously dispersed RGO simultaneously enhanced the strength and ductility of Zn scaffold. On one hand, the enhanced strength was ascribed to (i) the grain refinement caused by the pinning effect of RGO, (ii) the efficient load shift due to the huge specific surface area of RGO and the favorable interface bonding between RGO and Zn matrix, and (iii) the Orowan strengthening by the homogeneously distributed RGO. On the other hand, the improved ductility was owing to the RGO-induced random orientation of grain with texture index reducing from 20.5 to 7.3, which activated more slip systems and provided more space to accommodate dislocation. Furthermore, the cell test confirmed that RGO promoted cell growth and differentiation. This study demonstrated the great potential of RGO in tailoring the mechanical performance and cell behavior of Zn scaffold for bone repair.

The incorporation of hydroxyapatite (HAP) into poly-l-lactic acid (PLLA) matrix serving as bone scaffold is expected to exhibit bioactivity and osteoconductivity to those of the living bone. While too low degradation rate of HAP/PLLA scaffold hinders the activity because the embedded HAP in the PLLA matrix is difficult to contact and exchange ions with body fluid. In this study, biodegradable polymer poly (glycolic acid) (PGA) was blended into the HAP/PLLA scaffold fabricated by laser 3D printing to accelerate the degradation. The results indicated that the incorporation of PGA enhanced the degradation rate of scaffold as indicated by the weight loss increasing from 3.3% to 25.0% after immersion for 28 days, owing to the degradation of high hydrophilic PGA and the subsequent accelerated hydrolysis of PLLA chains. Moreover, a lot of pores produced by the degradation of the scaffold promoted the exposure of HAP from the matrix, which not only activated the deposition of bone like apatite on scaffold but also accelerated apatite growth. Cytocompatibility tests exhibited a good osteoblast adhesion, spreading and proliferation, suggesting the scaffold provided a suitable environment for cell cultivation. Furthermore, the scaffold displayed excellent bone defect repair capacity with the formation of abundant new bone tissue and blood vessel tissue, and both ends of defect region were bridged after 8 weeks of implantation.

Mg alloys have been regarded as revolutionary metallic biomaterials for biodegradable bone implants, but their applications are mainly blocked by the too rapid degradation in physiological environment. This study explores the dual alloying effects of Mn and/or Sn on the performance of Mg alloys prepared by selective laser melting. The observed microstructure indicated remarkable refinement of both the grains and intermetallic phases in the Mn- and/or Sn-containing alloys during the rapid solidification process. Moreover, approximately a half decrease in corrosion rate was observed for AZ61–0.4Mn-0.8Sn alloy with respect to AZ61 alloy. The improved corrosion behavior was primarily due to the enhanced protective effects of surface layers, in which Mn- and/or Sn-rich phases acted as a helpful barrier against medium penetration and thereby alleviated the current exchange with the matrix. In addition, the solute Mn and/or Sn positively shifted the corrosion potential, which also brought about a better corrosion resistance. Furthermore, the strength and hardness of the alloys were also effectively improved and comparable to those of cortical bone. This could be ascribed to the dissolved Mn and/or Sn atoms and the finely dispersed intermetallic phases, which might cause lattice distortion and precipitation hardening. Besides, the Mn- and/or Sn-containing alloys showed good cytocompatibility as indicated by the normal morphology and increased viability of MG-63 cells. These findings suggest that the developed AZ61-Mn-Sn alloy is a promising candidate for biodegradable bone implants.

Objective To understand the epidemic characteristics and drug resistance of Salmonella I4, [5], 12∶I∶-in Maoming City. Methods Salmonella I4, [5], 12∶I∶-were identified by serological method, and then antibiotic sensitivity of isolated Salmonella I4, [5], 12∶I∶-was tested by broth microdilution method. Results Among 476 strains of Salmonella from patients’ feces, 143 strains of Salmonella I4, [5], 12∶I∶-were detected, and the detection rate was 33.81%. The feces of patients were mainly from infants

Internet applications have different needs for network bandwidth,latency,jitter,and packet loss.However,the fact that the network and applications are decoupled makes it difficult for the network to be aware of an application’s requirements and ensure its quality of service (e.g.,service level agreement,SLA).A framework called application-aware IPv6 networking (APN6) was proposed,which could encapsulate applications’ requirements into packets.Networks could be aware of an application’s requirements and perform traffic steering and network resource adjustment.Besides,a secure access control mechanism was designed to solve application information forgery and tampering issues in APN6,which ensured that APN6 only provided services to legal users.

Magnesium (Mg) alloy shows great potential as bone implant owing to its favourable biocompatibility and degradability. In the present work, bioglass-reinforced Mg-based composite was manufactured via laser additive manufacturing. The results showed that too low a volumetric energy density (Ev) resulted in the appearance of open pores on the surface, which significantly deteriorated the densification behaviour. In contrast, too high an Ev caused the occurrence of the‘balling phenomenon’ with discontinuous surface, because of the excessive liquid formation and extended pool lifetime. Under a proper Ev of 185.19 J/mm3, favourable part with high densification rate was obtained. Meanwhile, the refined grains together with orderly dispersed reinforcing particles contributed to the enhanced mechanical properties. Significantly, the incorporated bioglass promoted the apatite deposition on Mg matrix, which served as an effective protection layer and reduced the degradation rate. Furthermore, it also improved the cell growth and differentiation, showing great potential in clinical bone repair.

Cell responses and mechanical properties are vital for scaffold in bone regeneration. Fe3O4 nanoparticles with excellent magnetism can provide magnetic stimulation for cell growth, while graphene oxide (GO) nanosheets are commonly used as reinforcement phases due to their high strength. However, Fe3O4 or GO is tended to agglomerate in matrix. In present study, a novel co-dispersed Fe3O4-GO nanosystem was constructed through electrostatic self-assembly of positively charged Fe3O4 (pFe3O4) on negatively charged GO nanosheets. In the nanosystem, pFe3O4 nanoparticles and GO nanosheets support each other, which effectively alleviates the π-π stacking between GO nanosheets and magnetic attraction between pFe3O4 nanoparticles. Subsequently, the nanosystem was incorporated into poly L-lactic acid (PLLA) scaffolds fabricated using selective laser sintering. The results confirmed that the pFe3O4-GO nanosystem exhibited a synergistic enhancement effect on stimulating cell responses by integrating the capturing effect of GO and the magnetic simulation effect of pFe3O4. The activity, proliferation and differentiation of cells grown on scaffolds were significantly enhanced. Moreover, the nanosystem also exhibited a synergistic enhancement effect on mechanical properties of scaffolds, since the pFe3O4 loaded on GO improved the efficiency of stress transfer in matrix. The tensile stress and compressive strength of scaffolds were increased by 67.1% and 132%, respectively. In addition, the nanosystem improved the degradation capability and hydrophilicity of scaffolds.

Zn has currently drawn great attention as potential orthopedic implant material due to its desirable biodegradability and good biocompatibility. In present study, Cu was introduced into Zn bone implant fabricated by laser powder bed fusion. Particularly, Cu dissolved in Zn liquid during melting, and subsequently partitioned ahead of the advancing liquid-solid interface during cooling. In this condition, a peritectic phase, ɛ-CuZn5, precipitated priority and acted as heterogeneous nucleation sites. It reacted with surrounding liquid phase to generate refined η-Zn grains, resulting in grain refinement and precipitation strengthening. As a result, the compressive yield strength, ultimate tensile strength and hardness were increased to 165 ± 7 MPa, 223 ± 4 MPa and 97 ± 2 HV, respectively. Moreover, Zn-Cu alloy exhibited a greatly enhanced antibacterial activity as compared with Zn, as the released Cu ion could damage cell membrane structure and inhibit plasmid/DNA replication. Furthermore, it also presented favorable biocompatibility as well as suitable degradation rate. It was demonstrated that Zn-Cu alloy may be a promising candidate as bone implant.

Blending Polyetheretherketone (PEEK) with Polyvinyl alcohol (PVA) is promising to obtain a composite scaffold combining the excellent biomechanical properties of PEEK and the remarkable degradability of PVA. However, the weak interfacial bonding between nonpolar PEEK and polar PVA would result in poor mechanical properties. In this study, owing to its unique amphiphilic properties, graphene oxide (GO) was employed to enhance the interfacial bonding between PEEK and PVA in PEEK/PVA scaffolds that were fabricated by laser 3D printing. On the one hand, the large π-conjugated structure of GO formed strong π-π interactions with the benzene rings in PEEK. On the other hand, the oxygen-containing groups of GO formed strong hydrogen bonds with the hydroxyl groups of PVA. As a result, the interfacial free energy between PEEK and PVA decreased from 37.4 to 29.6 mJ/m2 according to the harmonic-mean rule, and the PVA phase in PEEK matrix became much fine and uniform, indicating a reinforced interfacial bonding. Correspondingly, the strength and modulus of PEEK/PVA scaffolds increased by 97.16% and 147.06%, respectively, for a GO loading of 1%. Furthermore, the scaffolds exhibited good hydrophilicity and degradability, and promoted cell attachment and proliferation in vitro and osteogenic differentiation and bone regeneration in vivo.

A too slow degradation of iron (Fe) limits its orthopedic application. In this study, calcium chloride (CaCl2) was incorporated into a Fe-based biocomposite fabricated by laser additive manufacturing, with an aim to accelerate the degradation. It was found that CaCl2 with strong water absorptivity improved the hydrophilicity of the Fe matrix and thereby promoted the invasion of corrosive solution. On the other hand, CaCl2 could rapidly dissolve once contacting the solution and release massive chloride ion. Interestingly, the local high concentration of chloride ion effectively destroyed the corrosion product layer due to its strong erosion ability. As a result, the corrosion product layer covered on the Fe/CaCl2 matrix exhibited an extremely porous structure, thus exhibiting a significantly reduced corrosion resistance. Besides, in vivo cell testing proved that the Fe/CaCl2 biocomposite also showed favorable cytocompatibility.

Poly (lactic acid) (PLA) with good biodegradability, biocompatibility and processability has a wide application prospect in bone tissue engineering. However, PLA exhibits a very slow degradation rate, hindering the regeneration of new bone. In this study, the degradation mechanisms of PLA bone scaffold, including autocatalysis and non-catalysis, end-chain and random chain breaking, surface degradation and bulk degradation, were analyzed systematically, and the influence factors including crystallinity, molecular weight, pH, and so on, were introduced. On this basis, the strategies including blending, copolymerization, compounding and surface modification to accelerate the degradation of PLA were summarized, and the accelerating mechanisms were analyzed and discussed detailedly. In addition, rapid prototyping technologies with unique advantages on the structure and shape of scaffold were introduced. The mechanical properties (strength and modulus) and biological properties (in vivo and in vitro) of PLA scaffold were reviewed and discussed. Finally, the present problem of research including the simultaneous improvement of mechanical and degradation properties was put forward, and four-dimensional printing (4D printing) as an advanced technique which might bring new ideas to improve and extend the properties of PLA scaffold was mentioned.

Background: Ovarian cancer (OC)is a deadly gynecological malignancy worldwide. It is urgent to identify diagnostic biomarkers of OC to disclose the underlying mechanism.Methods and Materials: Bioinformatics analysis was used to identify target genes. Gene expression was detected and altered by qRT-PCR and cell transfection, respectively. The interaction between RP11-499E18.1 and PAK2, as well as that between PAK2 and SOX2, was determined using RNA pulldown, RNA immunoprecipitation (RIP), and co-immunoprecipitation (co-IP) assay, respectively. Localizations of RP11-499E18.1, PAK2, and SOX2 were respectively determined employing immunohistochemical (IHC), IF, and FISH. The regulatory effects of RP11-499E18.1, PAK2, and SOX2 on OC cell proliferation, migration, colony formation, epithelial–mesenchymal transition (EMT)-related factor expression, and SOX2 nuclear translocation were determined. Finally, the effects of RP11-499E18.1 and PAK2 expression on the tumor growth in nude mice were determined.Results: RP11-499E18.1, PAK2, and SOX2 were selected in our study. RP11-499E18.1 was downregulated, while PAK2 and SOX2 was upregulated in OC tissues and cells. RP11-499E18.1 coexists in the nucleus and cytoplasm of OC cells. There is an interaction between RP11-499E18.1 and PAK2, as well as PAK2 and SOX2 in OC cells. Alteration of RP11-499E18.1 and PAK2 expression both had no influence on PAK2 and SOX2 levels, but PAK2 upregulation notably augmented p-SOX2 level. RP11-499E18.1 overexpression suppressed OC cell proliferation, migration, and colony formation, as well as SOX2 nuclear translocation. Besides, it inhibited tumor growth in nude mice. However, these effects were notably reversed by PAK2 upregulation and eventually offset by SOX2 knockdown. Additionally, RP11-499E18.1 overexpression reduced PAK2–SOX2 interaction and SOX phosphorylation, and increased the binding of RP11-499E18.1 by PAK2.Conclusion: These lines of evidence demonstrated that RP11-499E18.1 might play its tumor suppressor roles in OC via regulation of the RP11-499E18.1–PAK2–SOX2 axis. This research indicated that RP11-499E18.1 might be used as a diagnostic biomarker for OC in the future.

Iron (Fe) has been highly anticipated as a bone implant material owing to the biodegradability and excellent mechanical properties, but limited by the slow degradation and poor bioactivity. In this study, novel Fe-palladium (Pd)-bredigite biocomposites were developed by selective laser melting aiming to improve both the degradation behavior and bioactivity of Fe. The results showed that most Pd formed Pd-rich intermetallic phases (IMPs) with a nearly continuous network while the bredigite phase was distributed at the grain boundaries. In addition, a large amount of much nobler IMPs formed micro-galvanic pairs with the Fe matrix, inducing tremendous micro-galvanic corrosion. The IMPs contained a high amount of Pd2+ with a high reduction potential, which further promoted the efficiency of micro-galvanic corrosion. Moreover, the rapid degradation of bredigite also facilitated the penetration of the corrosion medium. As a result, the Fe-4Pd-5bredigite biocomposite showed a uniform degradation with a rate that is 6 times that of Fe. Furthermore, the developed Fe-Pd-bredigite biocomposites also featured excellent bioactivity, cytocompatibility, and suitable mechanical properties as characterized by the rapid apatite deposition, normal proliferation of human osteoblast-like cells (MG-63), and comparable strength and microhardness with the native bone. Overall, this study opens a new avenue for improving both the degradation and bioactivity of Fe-based composites and may facilitate their applications as biodegradable implants for tissue/organ repair. Keywords: Iron-based biocomposites, Palladium, Bredigite, Biodegradability, Bioactivity, Selective laser melting

Abstract Background Premature ovarian insufficiency (POI) is a common disease in reproductive women. The pathogenesis of POI is not clear, although it is known that it involves the disorder of oocyte differentiation and development. The introduction of reprogramming human somatic cells into induced pluripotent stem cells (iPSCs) offers a unique opportunity to study many aspects of POI from cell differentiation in vitro that could ultimately lead to novel drug development and testing to help treat the disorder. Methods The fibroblasts from POI patients, including fragile X syndrome, abnormal karyotype (45, X; 45, X/46, XX; 45, XO and 47, XXX), and the gene mutation (FIGLA and GDF9) were reprogrammed to pluripotency status by retroviral transduction using defined factors. The morphology, growth characteristics, gene expression profiles, epigenetic status, and in vitro and in vivo differentiation potential of the POI-1-iPSCs (from fragile X syndrome) were analyzed. Then, POI-1-iPSCs were induced to differentiation into primordial germ cells (PGCs) with DNA methyltransferase inhibitors. Results The iPSCs were successfully generated from POI patients’ fibroblasts. The formed iPS clones have the same characteristics of human ESCs. POI-1-iPSCs were successfully generated with germline competence. The POI-1-iPSCs, with genotypes of fragile X syndrome, can be induced to differentiation into PGCs with high efficiency under our culture system by DNA demethylation. This study proved that disease-specific iPSC lines derived from POI patients could be generated and successfully differentiated into PGCs. Conclusions We established some novel, systemic cell models for the studying of the pathogenesis of POI patients. Second, DNA demethylation may accelerate the induction of human PGCs from iPSCs in vitro and the conclusion needs further exploration. This represents an important step in the novel approach for the study of the pathophysiology and potential egg resource for POI patients.

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.

Background: To develop a deep learning model to classify primary bone tumors from preoperative radiographs and compare performance with radiologists. Methods: A total of 1356 patients (2899 images) with histologically confirmed primary bone tumors and pre-operative radiographs were identified from five institutions’ pathology databases. Manual cropping was performed by radiologists to label the lesions. Binary discriminatory capacity (benign versus not-benign and malignant versus not-malignant) and three-way classification (benign versus intermediate versus malignant) performance of our model were evaluated. The generalizability of our model was investigated on data from external test set. Final model performance was compared with interpretation from five radiologists of varying level of experience using the Permutations tests. Findings: For benign vs. not benign, model achieved area under curve (AUC) of 0•894 and 0•877 on cross-validation and external testing, respectively. For malignant vs. not malignant, model achieved AUC of 0•907 and 0•916 on cross-validation and external testing, respectively. For three-way classification, model achieved 72•1% accuracy vs. 74•6% and 72•1% for the two subspecialists on cross-validation (p = 0•03 and p = 0•52, respectively). On external testing, model achieved 73•4% accuracy vs. 69•3%, 73•4%, 73•1%, 67•9%, and 63•4% for the two subspecialists and three junior radiologists (p = 0•14, p = 0•89, p = 0•93, p = 0•02, p

Graphene oxide has been proven to be a promising anti-penetrant shield for Mg alloys against their over-rapid biodegradation, but the weak interfacial bonding between graphene oxide and Mg alloy is the main obstacle for effective protection. In this study, magnesium oxide (MgO) nanoparticles are coated on reduced graphene oxide (RGO) surface and then introduced in AZ61 alloy by laser melting, expecting to strengthen the interfacial bonding between Mg matrix and RGO. The results reveal that MgO acts as an interfacial bridge between Mg matrix and RGO and constructs nanoscale-contact and distortion areas with RGO. Moreover, MgO and α-Mg form a semi-coherent interfacial structure, in which an orientation relationship of MgO (‾200)//α-Mg (‾110‾2) and a small planar disregistry of 7.5% are detected. These interfacial characteristics indicate strong bonding at both the RGO/MgO and MgO/α-Mg interfaces, which thereby strengthens the protective capability of RGO. Compared with AZ61-RGO composite and AZ61 alloy, the AZ61-RGO/MgO composite present 13.3% and 34.0% decreases in corrosion rate, respectively. Meanwhile, the compressive strength and hardness of AZ61 alloy are also enhanced owing to the strengthened interfacial bonding. These findings demonstrate that the RGO/Mg interfacial strengthening is a promising candidate for improving the degradation behavior of Mg alloys.

Polyvinylidene fluoride (PVDF), as a typical piezoelectric polymer, has a great potential in reconstructing the electrical microenvironment of bone tissue. In present study, graphene oxide (GO) was introduced into PVDF scaffold manufactured via selective laser sintering, aiming to enhance piezoelectric effect of PVDF by increasing β phase content. In detail, the oxygen-containing functional groups of GO could form strong hydrogen bonding with fluorine groups of PVDF. The interaction would force the fluorine groups to be arranged in parallel and perpendicular to the polymer chain, thereby inducing the transformation from α phase to β phase. Results demonstrated that the PVDF/0.3GO scaffold with improved β phase exhibited the maximal output voltage (~8.2 V) and current (~101.6 nA), which were improved by 82.2% and 68.2%, respectively, in comparison with pure PVDF. In vitro cell culture confirmed that enhanced electrical charges could significantly improve cell behavior. Moreover, the scaffold presented a 97.9% increase in compressive strength and 24.5% increase in tensile strength, which was attributed to GO reinforcements forming strong interaction with PVDF chains. These positive results suggested that the scaffold might have possible application in bone tissue engineering. Keywords: Bone regeneration, Piezoelectric, Polyvinylidene fluoride, Graphene oxide, Selective laser sintering

In present study, a strategy is presented to construct a magnetic micro-environment in poly-l-lactide/polyglycolic acid (PLLA/PGA) scaffolds fabricated via selective laser sintering by incorporating Fe3O4 magnetic nanoparticles (MNPs), aiming to enhance cell viability and promote bone regeneration. In the micro-environment, each nanoparticle provides a nanoscale magnetic field to activate cellular responses. The results in vitro demonstrated that the magnetic scaffolds not only stimulated cell adhesion and viability, but also enhanced proliferation rate and alkaline phosphatase activity. Meanwhile, the compressive strength and modulus were increased by 81.9% and 71.6%, respectively, which were determined by the rigid enhancement effect of MNPs. Moreover, the magnetic scaffolds were implanted into rabbit radius bone defect in vivo, and the results indicated that the magnetic scaffolds significantly induced substantial blood vessel tissue, fibrous tissue and new bone tissue formation at 2 months post-implantation, revealing the excellent bone regeneration capability. These positive results indicate that the construction of magnetic micro-environment in scaffolds is a working countermeasure to promote bone regeneration. Keywords: Magnetic scaffolds, Fe3O4 nanoparticles, Magnetic stimulation, Bone regeneration

Mg and its alloys have been identified as promising bone implant materials owing to their natural degradability, good biocompatibility and favorable mechanical properties. Nevertheless, the too fast degradation rate usually results in a premature disintegration of mechanical integrity and local hydrogen accumulation, which limit their clinical bone repair application. In this work, the current research status regarding Mg bone implants was systematically reviewed. The relevant strategies to enhance the corrosion resistance, including purification, alloying treatment, surface coating and Mg-based metal matrix composite, are comprehensively discussed. The fabricating techniques for Mg bone implants are also presented. Particularly, laser additive manufacturing can fabricate customized shape and complex porous structure basing on its unique additive manufacturing concept. More importantly, it can achieve rapid heating and cooling due to the characteristics of high laser energy density and good controllability, thereby regulating the microstructure and performance. Furthermore, the current challenges and future research perspectives are put forward. This work aims to offer some meaningful guidelines for researchers on the future study of Mg bone implants. Keywords: Mg bone implant, Degradation behavior, Additive manufacturing, Bone scaffold

The discrete secondary phases usually cause severe galvanic corrosion, thereby resulting in rapid degradation for Mg–Al alloys in orthopaedics application. In this study, CaO was introduced into Mg–Al–Zn (AZ61) alloy via selective laser melting (SLM) to ameliorate the characterisations of the secondary phases, with an aim to improve its corrosion behaviour. Results revealed that CaO reacted with Mg and Al in Mg–Al alloys during SLM, suppressing the formation of coarse Mg17Al12 phase and promoting the formation of (Mg, Al)2Ca phase. Meanwhile, the rapid solidification during SLM promoted the homogeneous precipitation of the second phase. As a result, inert (Mg, Al)2Ca phase homogeneously wrapped the Mg grains, which effectively protected them from the invasion of corrosion solution. Thus, the degradation rate was remarkably reduced from 0.073 to 0.031 mg cm–2 h–1. Furthermore, AZ61-9CaO exhibited good cytocompatibility. This work suggested that AZ61-9CaO was promising candidates for orthopaedics implants.

Zn possesses good biodegradability and biocompatibility, but its strength and hardness are insufficient for bone implants. In this study, Ag was introduced into Zn to improve the mechanical properties by selective laser melting. The results showed that Ag was dissolved in Zn, which generated constitutional undercooling in front of the advancing solid/liquid interface during solidification, making more nucleation events occur and thus refining the grains. When Ag content exceeded its solid solubility in Zn, AgZn3 phase is formed, which acted as active nucleation sites for Zn grains, further refining the grains. The refinement of the grains effectively hindered the plastic deformation and dislocation. As a result, the compressive strength and hardness were improved by about 100% and 116%, respectively. When Ag content continued increasing and became excessive, AgZn3 phase grew rapidly, coarsening the grains. Accordingly, the mechanical properties slightly decreased. These results demonstrated that the Zn–Ag alloys are potential implant biomaterials.

Abstract Background Cancer stem cells (CSCs) or tumor-initiating cells (TICs) represent a small population of cancer cells with self-renewal and tumor-initiating properties. Unlike the bulk of tumor cells, CSCs or TICs are refractory to traditional therapy and are responsible for relapse or disease recurrence in cancer patients. Stem cells have distinct metabolic properties compared to differentiated cells, and metabolic rewiring contributes to self-renewal and stemness maintenance in CSCs. Main body Recent advances in metabolomic detection, particularly in hyperspectral-stimulated raman scattering microscopy, have expanded our knowledge of the contribution of lipid metabolism to the generation and maintenance of CSCs. Alterations in lipid uptake, de novo lipogenesis, lipid droplets, lipid desaturation, and fatty acid oxidation are all clearly implicated in CSCs regulation. Alterations on lipid metabolism not only satisfies the energy demands and biomass production of CSCs, but also contributes to the activation of several important oncogenic signaling pathways, including Wnt/β-catenin and Hippo/YAP signaling. In this review, we summarize the current progress in this attractive field and describe some recent therapeutic agents specifically targeting CSCs based on their modulation of lipid metabolism. Conclusion Increased reliance on lipid metabolism makes it a promising therapeutic strategy to eliminate CSCs. Targeting key players of fatty acids metabolism shows promising to anti-CSCs and tumor prevention effects.

Poly‑l‑lactic acid (PLLA) is a promising bone repair material because of its good biocompatibility and natural degradability. Nevertheless, the poor mechanical properties and local inflammatory response limits its further application in bone repair. In this research, nano magnesium oxide (nMgO) was incorporated into PLLA scaffold manufactured by selective laser sintering technique. Results shown that nMgO with good affinity to PLLA could act as nucleating agent during crystallization process and effectively enhance the crystallinity of PLLA, which was proved by the isothermal behavior and non-isothermal behavior analysis. The evolution of crystallization was also achieved by polarized optical microscopy. Mechanical tests confirmed that the tensile strength, young modulus and Vickers hardness of PLLA/3nMgO was enhanced by 38%, 24% and 11%, respectively, as compared with PLLA. On the other hand, the incorporated nMgO neutralized the acid degradation by-products of PLLA, forming a weak alkaline environment which might contribute to avoiding sever local inflammation after implantation. Moreover, in vitro cell culture revealed an improved biocompatibility of PLLA/nMgO scaffolds. All these positive results suggested that PLLA/3nMgO scaffold was a potential material for bone repair application. Keywords: PLLA, Bone scaffolds, Mechanical properties, Degradation behavior, Biocompability

Poly-L-Lactic Acid (PLLA) is a bioabsorbable implant material due to its favorable biocompatibility and inherent degradability, while the insufficient mechanical strength hinders its further bone repair application. In present work, carbon nanotubes (CNTs) were introduced into PLLA scaffolds fabricated via selective laser sintering. It was found that the crystallinity of PLLA increased considerably since CNTs could promote the orderly stacking of its molecular chains, thereby improving the mechanical strength of PLLA scaffold. Furthermore, the fracture surface analysis revealed that CNTs acted as a bridge across the cracks and hindered their further expansion. Moreover, CNTs pulled out from the matrix to consume a large amount of fracture energy, which enhanced the resistance to external forces. As a consequence, the compressive strength, Vickers hardness and tensile strength of the scaffold were enhanced by 22.7%, 58.8% and 17.6%, respectively. Besides, the cells exhibited good attachment, spreading and proliferation on the scaffold. This study demonstrated that PLLA/CNTs scaffold was a promising candidate as bone implant.

Iron (Fe) has attracted intensive attention as a bone implant material because of its inherent biodegradability, favorable biocompatibility and mechanical properties. Nevertheless, it degrades too slowly in a physiological environment, which limits its further clinical application. In this work, mesoporous carbon (MC) was introduced into Fe bone implant manufactured via a laser-additive manufacturing process. Particularly, MC possesses a noble standard corrosion potential and excellent electrical conductivity, thus acting as an effective cathode and activating micro-galvanic corrosion in the Fe matrix. More importantly, its high specific surface area enhanced the area ratio between cathode and anode, which further enhanced the galvanic corrosion effect. As a consequence, the corrosion rate was enhanced from 0.09 to 0.24 mm/year based on immersion tests. Besides, Fe/MC composite exhibited good cytocompatibility, as well as excellent mechanical properties. The positive results proved that the Fe/MC composite shows great potential as a bone implant.

In order to improve the interfacial bonding between hydroxyapatite (HAP) and poly-l-lactic acid (PLLA), 2-Carboxyethylphosphonic acid (CEPA), a phosphonic acid coupling agent, was introduced to modify HAP nanoparticles. After this. the PLLA scaffold containing CEPA-modified HAP (C-HAP) was fabricated by selective laser sintering (frittage). The specific mechanism of interfacial bonding was that the PO32− of CEPA formed an electrovalent bond with the Ca2+ of HAP on one hand, and on the other hand, the −COOH of CEPA formed an ester bond with the −OH of PLLA via an esterification reaction. The results showed that C-HAP was homogeneously dispersed in the PLLA matrix and that it exhibited interconnected morphology pulled out from the PLLA matrix due to the enhanced interfacial bonding. As a result, the tensile strength and modulus of the scaffold with 20% C-HAP increased by 1.40 and 2.79 times compared to that of the scaffold with HAP, respectively. In addition, the scaffold could attract Ca2+ in simulated body fluid (SBF) solution by the phosphonic acid group to induce apatite layer formation and also release Ca2+ and PO43− by degradation to facilitate cell attachment, growth and proliferation.

Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs) and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs) are a family of transcripts longer than 200 nt without or with very low protein-coding potential. Recent studies have demonstrated that lncRNAs are widely involved in the regulation of lineage commitment and differentiation of stem cells through multiple mechanisms. In this review, we will summarize the roles and molecular mechanism of lncRNAs including H19, MALAT1, MODR, HOTAIR, DANCR, MEG3, HoxA-AS3, and MIAT in osteogenesis ossification; lncRNA ZBED3-AS1 and CTA-941F9.9, DANCR, and HIT in chondrogenic differentiation; and lncRNA DANCR in osteoclast differentiation. These findings will facilitate the development and application of novel molecular drugs which regulate the balance of bone formation and absorption.

Calcium sulfate (CaSO4), as a promising tissue repair material, has been applied widely due to its outstanding bioabsorbability and osteoconduction. However, fast disintegration, insufficient mechanical strength and poor bioactivity have limited its further application. In the study, CaSO4 scaffolds fabricated by using selective laser sintering were improved by adding 45S5 bioglass. The 45S5 bioglass enhanced stability significantly due to the bond effect of glassy phase between the CaSO4 grains. After immersing for four days in simulated body fluid (SBF), the specimens with 45S5 bioglass could still retain its original shape compared as opposed to specimens without 45S5 bioglass who experienced disintegration. Meanwhile, its compressive strength and fracture toughness increased by 80% and 37%, respectively. Furthermore, the apatite layer was formed on the CaSO4 scaffolds with 45S5 bioglass in SBF, indicating good bioactivity of the scaffolds. In addition, the scaffolds showed good ability to support the osteoblast-like cell adhesion and proliferation.

Diopside exhibits favorable potential for bone repair on account of the good mechanical performance, bioactivity and biocompatibility. In this paper, diopside scaffolds with high pore interconnectivity were successfully fabricated by laser three-dimensional (3D) printing. The microstructure and mechanical performance of the diopside scaffolds were studied. The experimental analysis indicated that diopside particles gradually fused together until a dense structure was built with an energy density increasing in the range between 2.4 and 4.8 J·mm-2. Meanwhile, compressive strength and fracture toughness increased gradually from 5.96 ± 0.88 MPa to 10.87 ± 0.55 MPa. However, mechanical properties decreased due to the appearance of voids when energy density were 5.4 and 6 J·mm-2. Simulated body fluid (SBF) tests showed that apatite crystals formed on the diopside scaffolds surface, and the apatite crystals increased with soaking time. Cell culture tests indicated the scaffolds supported the adhesion and growth of MG-63 cells. The study suggested that diopside scaffolds fabricated by laser 3D printing are promising candidates for bone tissue engineering.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.9845

Nano SiO2 and MgO particles were incorporated into β-tricalcium phosphate (β-TCP) scaffolds to improve the mechanical and biological properties. The porous cylindrical β-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 β-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 β-TCP to α-TCP was inhibited after the addition of MgO. The compressive strength of scaffold was improved from 3.12 ± 0.36 MPa (β-TCP) to 5.74 ± 0.62 MPa (β-TCP/SiO2), 9.02 ± 0.55 MPa (β-TCP/MgO) and 10.43 ± 0.28 MPa (β-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 β-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 β-TCP scaffold.

CaO-Al2O3-SiO2 (CAS) as a liquid phase was introduced into hydroxyapatite (HAp) to prepare bone scaffolds. The effects of the CAS content (1, 2, 3, 4 and 5 wt%) on microstructure and mechanical properties of HAp ceramics were investigated. The optimal compression strength, fracture toughness and Vickers hardness reached 22.22 MPa, 1.68 MPa·m1/2 and 4.47 GPa when 3 wt% CAS was added, which were increased by 105%, 63% and 11% compared with those of HAp ceramics without CAS, respectively. The improvement of the mechanical properties was attributed to the improved densification, which was caused by the solid particle to rearrange during liquid phase sintering. Moreover, simulated body fluid (SBF) study indicated the HAp ceramics could maintain the mechanical properties and form a bone-like apatite layer when they were immersed in SBF. Cell culture was used to evaluate biocompatibility of the HAp ceramics. The results demonstrated MG-63 cells adhered and spread well.

Carbon nanotubes are ideal candidates for the mechanical reinforcement of ceramic due to their excellent mechanical properties, high aspect ratio and nanometer scale diameter. In this study, the effects of multi-walled carbon nanotubes (MWCNTs) on the mechanical properties of diopside (Di) scaffolds fabricated by selective laser sintering were investigated. Results showed that compressive strength and fracture toughness improved significantly with increasing MWCNTs from 0.5 to 2 wt %, and then declined with increasing MWCNTs to 5 wt %. Compressive strength and fracture toughness were enhanced by 106% and 21%, respectively. The reinforcing mechanisms were identified as crack deflection, MWCNTs crack bridging and pull-out. Further, the scaffolds exhibited good apatite-formation ability and supported adhesion and proliferation of cells in vitro.