Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

Fabrication of a Nanoscale Magnesium/Copper Metal-Organic Framework on Zn-Based Guided Bone Generation Membranes for Enhancing Osteogenesis, Angiogenesis, and Bacteriostasis Properties.

Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal-organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu2+. As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn2+, Mg2+, and Cu2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.

Incorporation of Magnesium and Zinc Metallic Particles in PLGA Bi-layered Membranes with Sequential Ion Release for Guided Bone Regeneration.

Guided bone regeneration (GBR) membranes are commonly used for periodontal tissue regeneration. Due to the complications of existing GBR membranes, the design of bioactive membranes is still relevant. GBR membranes with an asymmetric structure can accommodate the functional requirements of different interfacial tissues. Here, poly(lactic acid-glycolic acid) (PLGA) was selected as the matrix for preparing a bi-layered membrane with both dense and porous structure. The dense layer for blocking soft tissues was incorporated with zinc (Zn) particles, while the porous layer for promoting bone regeneration was co-incorporated with magnesium (Mg) and Zn particles. Mg/Zn-embedded PLGA membranes exhibited 166% higher mechanical strength in comparison with pure PLGA membranes and showed suitable degradation properties with a sequential ion release behavior of Mg2+ first and continuously Zn2+. More importantly, the release of Zn2+ from bi-layered PLGA endowed GBR membranes with excellent antibacterial activity (antibacterial rate > 69.3%) as well as good cytocompatibility with MC3T3-E1 (mouse calvaria pre-osteoblastic cells) and HGF-1 (human gingival fibroblast cells). Thus, the asymmetric bi-layered PLGA membranes embedded with Mg and Zn particles provide a simple and effective strategy to not only reinforce the PLGA membrane but also endow membranes with osteogenic and antibacterial activity due to the continuous ion release profile, which serves as a promising candidate for use in GBR therapy.

Stiff Extracellular Matrix Promotes Invasive Behaviors of Trophoblast Cells.

The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell-ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the trophoblast model. We found that the spreading area of JAR cells, the formation of focal adhesions, and the polymerization of the F-actin cytoskeleton were all facilitated with increased ECM stiffness. Significantly, JAR cells also exhibited durotactic behavior on ECM with a gradient stiffness. Meanwhile, stiffness of the ECM affects the invasion of multicellular JAR spheroids. These results demonstrated that human trophoblast cells are mechanically sensitive, while the mechanical properties of the uterine microenvironment could play an important role in the implantation process.

Endowing biodegradable Zinc implants with dual-function of antibacterial ability and osteogenic activity by micro-addition of Mg and Ag (≤ 0.1 wt.%).

Infection remains the devastating complications associated with surgical fixation of bones fractured during trauma. In this study, we report a low-alloyed Zn-Mg-Ag that simultaneously has optimized strength degeneration profiles during degradation, outstanding antibacterial efficacy and osteogenic activity. Our results showed that Zn-0.05Mg-0.1Ag alloy had favorable mechanical properties (UTS: 247.8 ± 1.6 MPa, Elong.: 35 ± 2.2 %) and presented a better hold of mechanical integrity than pure Zn during 28 days corrosion, 2.6 % vs. 18.7 % reduction. After one-year of natural aging, the alloy still preserved an elongation of 24.07 ± 3.84 %. As verified by microbial cultures, Zn-0.05Mg-0.1Ag alloy demonstrated high antibacterial performance against Gram-positive and Gram-negative strains, as well as antibiotic-resistant strains (MRSA) in vitro and in vivo due to the synergistic antibacterial actions of Zn2+ and Ag+. Meanwhile, Zn-Mg-Ag alloy also exhibited enhanced viability, osteogenic differentiation, and gene expressions of osteoblasts in vitro, as well as promoted osteogenic activity than pure Zn in the femoral condyle defect repair model. The co-releasing of Zn, Mg and Ag ions did not induce toxic side effects. Collectively, low alloyed Zn-0.05Mg-0.1Ag indicated long-lasting mechanical integrity during degradation, and presented the ability to synergistically inhibit bacteria and promote osteogenesis, possessing tremendous potential in treating implant-associated infections. STATEMENT OF SIGNIFICANCE: Infection after fracture fixation (IAFF) remains the most common and serious side effects of orthopedic surgery. Additionally, widespread antibiotic use contributes to the development of multi-drug resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), which exacerbates IAFF treatment and prevention. IAFF treatment and prevention remain clinically challenging, so implants with dual antibacterial and osteogenic functions are in high demand. The antibacterial efficacy and osteogenic activity of low-alloyed Zn-Mg-Ag (≤0.1 wt.% Mg, Ag) alloys were investigated in vitro and in vivo. The results showed that micro addition of Mg and Ag could significantly improve osseointegration function, mechanical properties, and antibacterial performance. These quantification findings shed new light on the development and understanding of dual functional Zn-based orthopedic implants.

A surface-eroding poly(1,3-trimethylene carbonate) coating for magnesium based cardiovascular stents with stable drug release and improved corrosion resistance.

Magnesium alloys with integration of degradability and good mechanical performance are desired for vascular stent application. Drug-eluting coatings may optimize the corrosion profiles of magnesium substrate and reduce the incidence of restenosis simultaneously. In this paper, poly (trimethylene carbonate) (PTMC) with different molecular weight (50,000 g/mol named as PTMC5 and 350,000 g/mol named as PTMC35) was applied as drug-eluting coatings on magnesium alloys. A conventional antiproliferative drug, paclitaxel (PTX), was incorporated in the PTMC coating. The adhesive strength, corrosion behavior, drug release and biocompatibility were investigated. Compared with the PLGA control group, PTMC coating was uniform and gradually degraded from surface to inside, which could provide long-term protection for the magnesium substrate. PTMC35 coated samples exhibited much slower corrosion rate 0.05 µA/cm2 in comparison with 0.11 µA/cm2 and 0.13 µA/cm2 for PLGA and PTMC5 coated counterparts. In addition, PTMC35 coating showed more stable and sustained drug release ability and effectively inhibited the proliferation of human umbilical vein vascular smooth muscle cells. Hemocompatibility test indicated that few platelets were adhered on PTMC5 and PTMC35 coatings. PTMC35 coating, exhibiting surface erosion behavior, stable drug release and good biocompatibility, could be a good candidate as a drug-eluting coating for magnesium-based stent.

Current status and outlook of biodegradable metals in neuroscience and their potential applications as cerebral vascular stent materials.

Over the past two decades, biodegradable metals (BMs) have emerged as promising materials to fabricate temporary biomedical devices, with the purpose of avoiding potential side effects of permanent implants. In this review, we first surveyed the current status of BMs in neuroscience, and briefly summarized the representative stents for treating vascular stenosis. Then, inspired by the convincing clinical evidence on the in vivo safety of Mg alloys as cardiovascular stents, we analyzed the possibility of producing biodegradable cerebrovascular Mg alloy stents for treating ischemic stroke. For these novel applications, some key factors should also be considered in designing BM brain stents, including the anatomic features of the cerebral vasculature, hemodynamic influences, neuro-cytocompatibility and selection of alloying elements. This work may provide insights into the future design and fabrication of BM neurological devices, especially for brain stents.

Preparation of Magnetic-Luminescent Bifunctional Rapeseed Pod-Like Drug Delivery System for Sequential Release of Dual Drugs.

Drug delivery systems (DDSs) limited to a single function or single-drug loading are struggling to meet the requirements of clinical medical applications. It is of great significance to fabricate DDSs with multiple functions such as magnetic targeting or fluorescent labeling, as well as with multiple-drug loading for enhancing drug efficacy and accelerating actions. In this study, inspired by the dual-chamber structure of rapeseed pods, biomimetic magnetic-luminescent bifunctional drug delivery carriers (DDCs) of 1.9 ± 0.3 µm diameter and 19.6 ± 4.4 µm length for dual drug release were fabricated via double-needle electrospraying. Morphological images showed that the rapeseed pod-like DDCs had a rod-like morphology and Janus dual-chamber structure. Magnetic nanoparticles and luminescent materials were elaborately designed to be dispersed in two different chambers to endow the DDCs with excellent magnetic and luminescent properties. Synchronously, the Janus structure of DDCs promoted the luminescent intensity by at least threefold compared to single-chamber DDCs. The results of the hemolysis experiment and cytotoxicity assay suggested the great blood and cell compatibilities of DDCs. Further inspired by the core-shell structure of rapeseeds containing oil wrapped in rapeseed pods, DDCs were fabricated to carry benzimidazole molecules and doxorubicin@chitosan nanoparticles in different chambers, realizing the sequential release of benzimidazole within 12 h and of doxorubicin from day 3 to day 18. These rapeseed pod-like DDSs with excellent magnetic and luminescent properties and sequential release of dual drugs have potential for biomedical applications such as targeted drug delivery, bioimaging, and sustained treatment of diseases.

In vitro degradation, biocompatibility and antibacterial properties of pure zinc: assessing the potential of Zn as a guided bone regeneration membrane.

Membrane exposure is a common complication after the guided bone regeneration (GBR) procedure and has a detrimental influence on the bone regeneration outcomes, while the commercially available GBR membranes show limited exposure tolerance. Recently, zinc (Zn) has been suggested as a promising material to be used as a barrier membrane in GBR therapy for bone augmentation. In this study, the degradation behavior in artificial saliva solution, cytotoxicity and antibacterial activity of pure Zn were investigated to explore its degradation and associated biocompatibility in the case of premature membrane exposure. The results indicated that the degradation rate of Zn in artificial saliva solution was about 31.42 µm year-1 after 28 days of immersion. The corrosion products on the Zn surface were mainly composed of Zn3(PO4)2, Ca3(PO4)2, CaHPO4, Zn5(CO3)2(OH)6 and ZnO. Besides, Zn presented an acceptable in vitro HGF cytocompatibility and a high antibacterial activity against Porphyromonas gingivalis. The preliminary results demonstrate that pure Zn exhibits appropriate degradation behavior, adequate cell compatibility and favorable antibacterial properties in the oral environment and is thus believed to sustain profitable function when membrane exposure occurs. The results provided new insights for understanding the exposure tolerance of Zn based membranes and are beneficial to their clinical applications.

Effect of strain on degradation behaviors of WE43, Fe and Zn wires.

The biodegradable metallic devices undergo stress/strain-induced corrosion when they are used for load-bearing applications. The stress/strain induced-corrosion behavior causes differences in corrosion rate, corrosion morphology, strain distribution and mechanical performance of the devices. One representative example is the biodegradable stent. Biodegradable stents undergo complex inhomogeneous deformation that can cause dramatic non-uniform stent degradation, resulting in stress concentration and stents failure. The degradation of biodegradable devices requires special attention to the mutual effect between the applied strain and degradation. The quantitative relationship between strain and corrosion of the sample alloys (WE43, Fe and Zn), selected from three typical biodegradable metals, is firstly investigated and compared in this study. The in vitro degradation and the strength retention of WE43, Fe and Zn wires were investigated under different elastic and plastic strain levels ranging from 0.1% to 30%. The results indicated that the applied strain could bring down the corrosion potential, increase corrosion current and accelerate the degradation of three biodegradable metals. Specifically, remarkable enhanced localized corrosion was observed for plastic strained WE43 compared with those with elastic strains. This localized corrosion morphology significantly accelerated the strength decline at first, while the differences diminished with longer immersion period. Fe and Zn exhibited increased degradation with plastic strain applications than those under elastic strains. However, the degradation was not further increased with the increasing magnitude of plastic strains. Moreover, the bended wires were subcutaneously implanted in the dorsal aspect of the rats and the effect of bending deformation on in vitro and in vivo degradation of three metallic wires were also compared. The U-bended WE43 wires suffered more severe in vitro degradation at the stress concentrated region. Surprisingly, the early fracture of the undeformed regions was observed in the in vivo test. In conclusion, the corrosion rate, corrosion morphology and mechanical properties of WE43, Fe and Zn was sensitive to magnitude of the applied strains. The quantification results provided new insights into understanding the strain-dependent corrosion of three biodegradable metals both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Biodegradable implants are subjected to various mechanical environment during the deployment and subsequent physiological activity. It is necessary to have a clear understanding of the effects of the applied stress on degradation. This study addresses the quantitative effects of applied strain/stress on the in vitro and in vivo degradation of three typical biodegradable metals (Mg, Fe and Zn). These quantification results provide new insights into understanding the strain-induced corrosion of three metals.

In vitro and in vivo degradation behavior of Mg-2Sr-Ca and Mg-2Sr-Zn alloys.

Magnesium alloys with integration of degradability and good mechanical performance are desired for orthopedic implants. In this paper, Mg-2Sr-Ca and Mg-2Sr-Zn alloys were prepared and the degradation as well as the bone response were investigated. Compared with the binary Mg-2Sr alloys, the addition of Ca and Zn improved the in vitro and in vivo corrosion resistance. Mg-2Sr-Ca and Mg-2Sr-Zn alloys exhibited more uniform corrosion and maintained the configuration of the implants 4 weeks post-implantation. The in vivo corrosion rates were 0.85 mm/yr for Mg-2Sr-Zn and 1.10 mm/yr for Mg-2Sr-Ca in comparison with 1.37 mm/yr for Mg-2Sr. The in vitro cell tests indicated that Mg-2Sr-Ca and Mg-2Sr-Zn alloys exhibited higher MG63 cell viability than Mg-2Sr alloy. Furthermore, these two alloys can promote the mineralization and new bone formation without inducing any significant adverse effects and this sound osteogenic properties suggest its attractive clinical potential.

Positive Effect of Magnetic-Conductive Bifunctional Fibrous Scaffolds on Guiding Double Electrical and Magnetic Stimulations to Pre-Osteoblasts.

Development of bone tissue engineering has provided a promising method for bone rehabilitation. Tissue engineering scaffolds with magnetic or conductive properties may conduct electric or magnetic signals and bring out synergetic promoting effect to cells growth. In this work, polypyrrole (PPy)/Fe3O4/polylactic acid-glycolic acid (PLGA) magnetic-conductive bifunctional fibrous scaffolds were prepared through in-situ polymerization of pyrrole on Fe3O4/PLGA fibers. The prepared magnetic-conductive bifunctional PPy/Fe3O4/PLGA fibrous scaffolds showed good conductive and magnetic properties to deliver electrical and magnetic signals. The PPy/Fe3O4/PLGA fibrous scaffolds had a conductivity of 0.58 S/cm at 180 mM pyrrole and still remained with good fibrous morphology. MC3T3-E1 pre-osteoblasts inoculated on PPy/Fe3O4/ PLGA scaffolds under double electrical stimulation (ES) and magnetic stimulation (MS) demonstrated highest cell viabilities compared with those under single ES, MS or without any stimulation. The enhancement of cell viabilities by the Fe3O4/PLGA and PPy/Fe3O4/PLGA fibrous scaffolds from 1 to 5 d culture indicate that both of them had good biocompatibility. MS can also induce cell alignment arrangement on the magnetic scaffolds according to resultant cell scanning electron microscope (SEM) images. In addition, better hydrophilicity and thermal stability of the PPy/Fe3O4/PLGA fibrous scaffolds, as compared to Fe3O4/PLGA fibrous scaffolds, allowed the bifunctional scaffolds wide application in bone tissue engineering.

Biodegradable Magnesium-Incorporated Poly(l-lactic acid) Microspheres for Manipulation of Drug Release and Alleviation of Inflammatory Response.

Poly(l-lactic acid) (PLLA) and magnesium (Mg) are widely concerned biodegradable materials, but during in vivo implantation, the former produces acidic degradation byproducts and can easily induce inflammation in surrounding tissues, whereas the latter is fast corroded and generates alkaline products. The purpose of this study is to develop Mg/PLLA composite microspheres as a novel delivery system, in which Mg particles are used to regulate the drug release profile and suppress PLLA-induced inflammatory response. Morphological observation shows that multiple Mg particles are dispersed both on the surface and in the interior of composite microspheres. In vitro release study indicates that by varying the Mg contents or its particle sizes, the internal connectivity of composite microspheres is changed during hydrolytic degradation, and drug delivery can be facilely manipulated with tunable release patterns. In vivo release study further confirms the feasibility of Mg/PLLA microspheres for tailoring drug release in a physiological environment. The animal experiment reveals that Mg particles can alleviate macrophage infiltration and inflammatory cytokine expression. These results demonstrate the availability of using biodegradable Mg particles to manipulate drug release as well as alleviate PLLA-induced inflammation. The present Mg/PLLA composite microspheres have potential applications in controlled delivery of various therapeutic agents, especially some growth factors, for bone regeneration.

Degradation and biocompatibility of a series of strontium substituted hydroxyapatite coatings on magnesium alloys.

There has been a surge in the research on magnesium (Mg) alloys as a promising selection for biomaterials application. However, as a foremost drawback, the fast degradation of Mg alloys limits its clinical use. In this study, a series of Sr-HA coatings with the Sr content ranging between 10-100% were prepared on Mg alloys, in order to control the degradation and enhance the osteoblast response. Microstructure analysis indicated the formation of Ca10-x Sr x (PO4)6(OH)2 coatings with the thickness ranging between 28-35 µm. The degradation results suggested that an increase in the Sr content in the coatings led to the decreasing degradation rate of the Sr-HA coated Mg. 100% Sr-HA coatings provided the best corrosion protective effect with nearly no hydrogen evolution during 10 days' immersion in Hank's solution. The in vitro cell biocompatibility was evaluated with MC3T3-E1 osteoblasts using the extract assay. In each case the released Sr affected the osteoblast proliferation and the expression of osteogenesis markers including, ALP, Col-I and RUNX2, in a Sr concentration-dependent manner. These results suggest that Sr-HA coating is a promising combination for controlling the degradation and enhancing the cytocompatibility of Mg alloys. The degradation and osteoblast response could be simply controlled through the adjustment of Sr content in the coatings.

Effect of stress on corrosion of high-purity magnesium in vitro and in vivo.

Magnesium-based implants are subjected to complicated stresses during implantation in the human body. The stress effects on corrosion of magnesium (Mg) in vitro were investigated in previous studies, whereas in this study, the corrosion behaviors of high-purity (HP) Mg under stress were comparatively studied in vitro in Hank's solution and in vivo in the subcutaneous environment of rats. Loading devices were designed to apply compressive stress (15.1 ±â€¯0.5 MPa) and tensile stress (13.2 ±â€¯0.2 MPa) on HP Mg specimens both in vitro and in vivo. Corrosion rates of HP Mg were characterized by mass and volume losses. It was shown that the applied compressive stress had no effect on in vitro corrosion behaviors and the applied tensile stress accelerated the in vitro corrosion, thereby causing severe pitting corrosions and stress corrosion cracking (SCC). However, there was no significant change for corrosion behaviors in vivo under neither compressive stress nor tensile stress. Severe pitting corrosion and SCC did not occur in vivo. Histological evaluation revealed that a fibrotic capsule induced by foreign body reaction was formed on the corrosion surfaces of HP Mg in the subcutaneous environment. It was proposed that the fibrotic capsule suppressed the effects of stress in vivo by protecting the corrosion surfaces. These results provided new insights into understanding the stress effects on the corrosion of Mg both in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Mg and its alloys have shown potential as biodegradable metallic materials. During implantation, Mg is subjected to various mechanical environments in the human body. It is necessary to have a clear understanding of different effects of stress on Mg corrosion. However, few studies were performed in vivo. It is important to analyze the effect of quantitative stress on Mg corrosion in vivo. Therefore, in this study, quantitative stresses were applied on Mg both in vitro and in vivo. The effects of stress on in vitro and in vivo corrosions of Mg were investigated and compared.

The effect of tensile and fluid shear stress on the in vitro degradation of magnesium alloy for stent applications.

Magnesium alloys have gained great attention as biodegradable materials for stent applications. Cardiovascular stents are continuously exposed to different types of mechanical loadings simultaneously during service, including tensile, compressive and fluid shear stress. In this study, the in vitro degradation of WE43 wires was investigated under combined effect of tensile loading and fluid shear stress and compared with that experienced an individual loading condition. For the individual mechanical loading treatment, the degradation of magnesium wires was more severely affected by tensile loading than fluid shear stress. Under tensile loading, magnesium wires showed faster increment of corrosion rates, loss of mechanical properties and localized corrosion morphology with the increasing tensile loadings. With the combined stress, smaller variation of the corrosion rates as well as the slower strength degeneration was shown with increasing stress levels, in comparison with the individual treatment of tensile loading. This study could help to understand the effect of complex stress condition on the corrosion of magnesium for the optimization of biodegradable magnesium stents.

A quantitative study on magnesium alloy stent biodegradation.

Insufficient scaffolding time in the process of rapid corrosion is the main problem of magnesium alloy stent (MAS). Finite element method had been used to investigate corrosion of MAS. However, related researches mostly described all elements suffered corrosion in view of one-dimensional corrosion. Multi-dimensional corrosions significantly influence mechanical integrity of MAS structures such as edges and corners. In this study, the effects of multi-dimensional corrosion were studied using experiment quantitatively, then a phenomenological corrosion model was developed to consider these effects. We implemented immersion test with magnesium alloy (AZ31B) cubes, which had different numbers of exposed surfaces to analyze differences of dimension. It was indicated that corrosion rates of cubes are almost proportional to their exposed-surface numbers, especially when pitting corrosions are not marked. The cubes also represented the hexahedron elements in simulation. In conclusion, corrosion rate of every element accelerates by increasing corrosion-surface numbers in multi-dimensional corrosion. The damage ratios among elements with the same size are proportional to the ratios of corrosion-surface numbers under uniform corrosion. The finite element simulation using proposed model provided more details of changes of morphology and mechanics in scaffolding time by removing 25.7% of elements of MAS. The proposed corrosion model reflected the effects of multi-dimension on corrosions. It would be used to predict degradation process of MAS quantitatively.

Role of Recursive Partitioning Analysis and Graded Prognostic Assessment on Identifying Non-Small Cell Lung Cancer Patients with Brain Metastases Who May Benefit from Postradiation Systemic Therapy.

BACKGROUND: The role of postradiation systemic therapy in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) was controversial. Thus, we explored the role of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) and graded prognostic assessment (GPA) in identifying population who may benefit from postradiation systemic therapy. METHODS: The clinical data of NSCLC patients with documented BM from August 2007 to April 2015 of two hospitals were studied retrospectively. Cox regression was used for multivariate analysis. Survival of patients with or without postradiation systemic therapy was compared in subgroups stratified according to RTOG-RPA or GPA. RESULTS: Of 216 included patients, 67.1% received stereotactic radiosurgery (SRS), 24.1% received whole-brain radiation therapy (WBRT), and 8.8% received both. After radiotherapy, systemic therapy was administered in 58.3% of patients. Multivariate analysis found that postradiation systemic therapy (yes vs. no) (hazard ratio [HR] = 0.361, 95% confidence interval [CI] = 0.202-0.648, P = 0.001), radiation technique (SRS vs. WBRT) (HR = 0.462, 95% CI = 0.238-0.849, P = 0.022), extracranial metastasis (yes vs. no) (HR = 3.970, 95% CI = 1.757-8.970, P = 0.001), and Karnofsky performance status (<70 vs. ≥70) (HR = 5.338, 95% CI = 2.829-10.072, P < 0.001) were independent factors for survival. Further analysis found that subsequent tyrosine kinase inhibitor (TKI) therapy could significantly reduce the risk of mortality of patients in RTOG-RPA Class II (HR = 0.411, 95% CI = 0.183-0.923, P = 0.031) or with a GPA score of 1.5-2.5 (HR = 0.420, 95% CI = 0.182-0.968, P = 0.042). However, none of the subgroups stratified according to RTOG-RPA or GPA benefited from the additional conventional chemotherapy. CONCLUSION: RTOG-RPA and GPA may be useful to identify beneficial populations in NSCLC patients with BM if TKIs were chosen as postradiation systemic therapy.

The promoting effect on pre-osteoblast growth under electrical and magnetic double stimulation based on PEDOT/Fe3O4/PLGA magnetic-conductive bi-functional scaffolds.

Electrical stimulation (ES) and magnetic stimulation (MS) can promote bone tissue formation in vivo. Loading ES and MS simultaneously would be very beneficial for bone tissue construction in vitro or in vivo. Magnetic-conductive bi-functional scaffolds which are favorable for the transfer of ES and MS, could further facilitate bone cell/tissue growth. Poly(3,4-ethylenedioxythiophene) (PEDOT)/Fe3O4/polylactic acid-co-glycolic acid (PLGA) magnetic-conductive bi-functional fibrous scaffolds were prepared through in situ polymerization of EDOT on Fe3O4/PLGA fibers. MC3T3-E1 pre-osteoblasts were incubated on the PEDOT/Fe3O4/PLGA fibrous scaffolds and were stimulated by electrical, magnetic and electrical-magnetic signals respectively to detect the impact of different stimulation on cell viability. The measured results show that the scaffolds possess good conductivity and superparamagnetic responsiveness. Furthermore, both electrical and magnetic stimulation promoted cell proliferation and magnetic stimulation could induce cell alignment arrangement. Meanwhile, under electrical-magnetic double stimulation, cell viability was much higher than for cells under single electrical or magnetic stimulation. The growth promoting effects of PEDOT/Fe3O4/PLGA fibrous scaffolds under electrical-magnetic double stimulation has great practical potential for bone tissue engineering.