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    Dynamic protein corona influences immune-modulating osteogenesis in magnetic nanoparticle (MNP)-infiltrated bone regeneration scaffolds in vivo. Zhu Yue,Jiang Peipei,Luo Bin,Lan Fang,He Jing,Wu Yao Nanoscale An inflammatory reaction initiates fracture healing and directly influences the osteoinductive effect of the magnetic hydroxyapatite (MHA) scaffold, but the underlying mechanism is yet to be elucidated. Protein corona as a real biological identity of a biomaterial significantly affects the biological function of the bone regenerative scaffold. Hence, we developed a simple and effective in vivo dynamic model for the protein corona of MHA scaffolds to predict the correlation between the inflammatory reaction and bone wound healing, as well as the underlying mechanism governing such a process. Certain proteins including proteins related to the immune response and inflammation, bone and wound healing, extracellular matrix, cell behavior, and signaling increased in the protein corona of the magnetic nanoparticle (MNP)-infiltrated scaffolds in a time-dependent manner. Moreover, the enriched proteins related to the immune response and inflammation adsorbed on the MHA scaffolds correlated well with the proteins that significantly enhanced bone wound healing, as suggested by the same variation tendency of the proteins related to bone and wound healing, and immune response and inflammation. The presence of MNPs suppressed the chronic inflammatory responses and highly promoted the acute inflammatory responses. More importantly, the activation of the acute inflammatory responses led to the recruitment of immune cells, remodeling of the extracellular matrix and even the acceleration of bone healing. The bone repair in vivo model and inflammatory cytokine in vitro model results further corroborated the critical involvement of inflammatory reaction in enhancing bone wound healing. This opens up the great potential of protein corona formation to understand the complicated mechanisms involved in immune-modulated bone wound healing. 10.1039/c8nr08614a
    Preparation and characterization of the collagen/cellulose nanocrystals/USPIO scaffolds loaded kartogenin for cartilage regeneration. Yang Wei,Zheng Yuanyuan,Chen Jie,Zhu Qiyu,Feng Longbao,Lan Yong,Zhu Ping,Tang Shuo,Guo Rui Materials science & engineering. C, Materials for biological applications The regeneration of cartilage is a challenging problem for lack of innate abilities to mount a sufficient healing response. Kartogenin (KGN), an emerging chondroinductive non-protein small molecule, bound to the surface of the ultrasmall super-paramagnetic iron-oxide (USPIO) by innovational one-step technology, followed by being incorporated into the cross-linking collagen/cellulose nanocrystals (Col/CNC) bioactive scaffolds to stimulate an appropriate microenvironment for the growth and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs), thus facilitating the formation of chondrocyte. Herein, USPIO not only served as a carrier for small molecule drugs, but also as MRI contrast agents, which can non-invasively monitor the degradation of the scaffolds and the self-repair capacity of cartilage. In vitro studies showed that the KGN could release from the composite scaffolds in a sustained and stable manner and promote the chondrogenic differentiation of BMSCs based on UV spectrophotometry test, and specific markers analysis. Of note, USPIO labeled composite scaffolds retained their stability without loss of relaxation rate the composite scaffolds can be a promising biomaterials for cartilage repair, with the function of noninvasive visualization and semiquantitative analysis of scaffolds degradation and neocartilage. 10.1016/j.msec.2019.02.071
    Magnetothermal heating facilitates the cryogenic recovery of stem cell-laden alginate-FeO nanocomposite hydrogels. Zhang Xiaozhang,Zhao Gang,Cao Yuan,Haider Zeeshan,Wang Meng,Fu Jianping Biomaterials science Constructs of magnetic nanocomposite hydrogels microencapsulated with stem cells are of great interest as smart materials for tissue engineering and regenerative medicine. Due to the short shelf life of such biocomposites at an ambient temperature, their long-term storage and banking at cryogenic temperatures are essential for the "off-the-shelf" availability of such biocomposites for widespread clinical applications. However, high-quality cryogenic recovery of stem cell-nanocomposite hydrogel constructs has not yet been achieved due to the damage to cells and/or microstructures of hydrogel constructs caused by ice formation, particularly during warming from cryogenic temperatures. Herein, stem cell-magnetic nanocomposite hydrogel constructs, which have an inherent magnetothermal property provided by embedded magnetic nanoparticles, are explored to achieve ultra-rapid cryogenic warming. The binding of water molecules by the hydrogel combined with the magnetothermal heating greatly suppressed ice formation during both cryogenic cooling and warming. Thus, the cryogenic recovery of nanocomposite hydrogel constructs with intact microstructures and fully functional stem cells from ultra-low temperatures was successfully achieved. We further demonstrated that magnetic nanocomposite hydrogels microencapsulated with stem cells could be conveniently manipulated for a self-assembled 3D culture. Together, we have developed a highly efficient and easy-to-perform approach for the cryogenic recovery of stem cell-encapsulated magnetic nanocomposite hydrogel constructs. Our results will facilitate the applications of such stem cell-magnetic nanocomposite hydrogels in regenerative medicine and tissue engineering. 10.1039/c8bm01004h
    Novel magnetic calcium phosphate-stem cell construct with magnetic field enhances osteogenic differentiation and bone tissue engineering. Xia Yang,Chen Huimin,Zhao Yantao,Zhang Feimin,Li Xiaodong,Wang Lin,Weir Michael D,Ma Junqing,Reynolds Mark A,Gu Ning,Xu Hockin H K Materials science & engineering. C, Materials for biological applications Superparamagnetic iron oxide nanoparticles (IONPs) are promising bioactive additives to fabricate magnetic scaffolds for bone tissue engineering. To date, there has been no report on osteoinductivity of IONP-incorporated calcium phosphate cement (IONP-CPC) scaffold on stem cells using an exterior static magnetic field (SMF). The objectives of this study were to: (1) develop a novel magnetic IONP-CPC construct for bone tissue engineering, and (2) investigate the effects of IONP-incorporation and SMF application on the proliferation, osteogenic differentiation and bone mineral synthesis of human dental pulp stem cells (hDPSCs) seeded on IONP-CPC scaffold for the first time. The novel magnetic IONP-CPC under SMF enhanced the cellular performance of hDPSCs, yielding greater alkaline phosphatase activities (about 3-fold), increased expressions of osteogenic marker genes, and more cell-synthesized bone minerals (about 2.5-fold), compared to CPC control and nonmagnetic IONP-CPC. In addition, IONP-CPC induced more active osteogenesis than CPC control in rat mandible defects. These results were consistent with the enhanced cellular performance by magnetic IONP in media under SMF. Moreover, nano-aggregates were detected inside the cells by transmission electron microscopy (TEM). Therefore, the enhanced cell performance was attributed to the physical forces generated by the magnetic field together with cell internalization of the released magnetic nanoparticles from IONP-CPC constructs. 10.1016/j.msec.2018.12.120
    Iron oxide nanoparticles in liquid or powder form enhanced osteogenesis via stem cells on injectable calcium phosphate scaffold. Xia Yang,Zhao Yantao,Zhang Feimin,Chen Bo,Hu Xiantong,Weir Michael D,Schneider Abraham,Jia Lu,Gu Ning,Xu Hockin H K Nanomedicine : nanotechnology, biology, and medicine The objectives of this study were to incorporate iron oxide nanoparticles (IONPs) into calcium phosphate cement (CPC) to enhance bone engineering, and to investigate the effects of IONPs as a liquid or powder on stem cells using IONP-CPC scaffold for the first time. IONP-CPCs were prepared by adding 1% IONPs as liquid or powder. Human dental pulp stem cells (hDPSCs) were seeded. Subcutaneous implantation in mice was investigated. IONP-CPCs had better cell spreading, and greater ALP activity and bone mineral synthesis, than CPC control. Subcutaneous implantation for 6 weeks showed good biocompatibility for all groups. In conclusion, incorporating IONPs in liquid or powder form both substantially enhanced hDPSCs on IONP-CPC scaffold and exhibited excellent biocompatibility. IONP incorporation as a liquid was better than IONP powder in promoting osteogenic differentiation of hDPSCs. Incorporating IONPs and chitosan lactate together in CPC enhanced osteogenesis of hDPSCs more than using either alone. 10.1016/j.nano.2019.102069
    Carbon nanotube/iron oxide hybrid particles and their PCL-based 3D composites for potential bone regeneration. Świętek Małgorzata,Brož Antonín,Tarasiuk Jacek,Wroński Sebastian,Tokarz Waldemar,Kozieł Agata,Błażewicz Marta,Bačáková Lucie Materials science & engineering. C, Materials for biological applications This study describes the preparation, and evaluates the biocompatibility, of hydroxylated multi-walled carbon nanotubes (fCNTs) functionalized with magnetic iron oxide nanoparticles (IONs) creating hybrid nanoparticles. These nanoparticles were used for preparing a composite porous poly(ε-caprolactone) scaffolds for potential utilization in regenerative medicine. Hybrid fCNT/ION nanoparticles were prepared in two mass ratios - 1:1 (H1) and 1:4 (H4). PCL scaffolds were prepared with various concentrations of the nanoparticles with fixed mass either of the whole nanoparticle hybrid or only of the fCNTs. The hybrid particles were evaluated in terms of morphology, composition and magnetic properties. The cytotoxicity of the hybrid nanoparticles and the pure fCNTs was assessed by exposing the SAOS-2 human cell line to colloids with a concentration range from 0.01 to 1 mg/ml. The results indicate a gradual increase in the cytotoxicity effect with increasing concentration. At low concentrations, interestingly, SAOS-2 metabolic activity was stimulated by the presence of IONs. The PCL scaffolds were characterized in terms of the scaffold architecture, the dispersion of the nanoparticles within the polymer matrix, and subsequently in terms of their thermal, mechanical and magnetic properties. A higher ION content was associated with the presence of larger agglomerates of particles. With exception of the scaffold with the highest content of the H4 nanoparticle hybrid, all composites were superparamagnetic. In vitro tests indicate that both components of the hybrid nanoparticles may have a positive impact on the behavior of SAOS-2 cells cultivated on the PCL composite scaffolds. The presence of fCNTs up to 1 wt% improved the cell attachment to the scaffolds, and a content of IONs below 1 wt% increased the cell metabolic activity. 10.1016/j.msec.2019.109913
    A Magnetic Iron Oxide/Polydopamine Coating Can Improve Osteogenesis of 3D-Printed Porous Titanium Scaffolds with a Static Magnetic Field by Upregulating the TGFβ-Smads Pathway. Huang Zhenfei,He Yu,Chang Xiao,Liu Jieying,Yu Lingjia,Wu Yuanhao,Li Yaqian,Tian Jingjing,Kang Lin,Wu Di,Wang Hai,Wu Zhihong,Qiu Guixing Advanced healthcare materials 3D-printed porous titanium-aluminum-vanadium (Ti6Al4V, pTi) scaffolds offer surgeons a good option for the reconstruction of large bone defects, especially at the load-bearing sites. However, poor osteogenesis limits its application in clinic. In this study, a new magnetic coating is successfully fabricated by codepositing of Fe O nanoparticles and polydopamine (PDA) on the surface of 3D-printed pTi scaffolds, which enhances cell attachment, proliferation, and osteogenic differentiation of hBMSCs in vitro and new bone formation of rabbit femoral bone defects in vivo with/without a static magnetic field (SMF). Furthermore, through proteomic analysis, the enhanced osteogenic effect of the magnetic Fe O /PDA coating with the SMF is found to be related to upregulate the TGFβ-Smads signaling pathway. Therefore, this work provides a simple protocol to improve the osteogenesis of 3D-printed porous pTi scaffolds, which will help their application in clinic. 10.1002/adhm.202000318
    Impact of the magnetic field on 3T3-E1 preosteoblasts inside SMART silk fibroin-based scaffolds decorated with magnetic nanoparticles. Tanasa Eugenia,Zaharia Catalin,Hudita Ariana,Radu Ionut-Cristian,Costache Marieta,Galateanu Bianca Materials science & engineering. C, Materials for biological applications This paper reports the impact of the magnetic field on 3T3-E1 preosteoblasts within silk-fibroin scaffolds decorated with magnetic nanoparticles. Scaffolds were prepared from silk fibroin and poly(2-hydroxyethyl methacrylate) template in which magnetite nanoparticles were embedded. The presence of the magnetite specific peaks within scaffolds compositions was evidenced by RAMAN analysis. Structural investigation was done by XRD analysis and morphological information including internal structure was obtained through SEM analysis. Geometrical evaluation (size and shape), crystalline structure of magnetic nanoparticles and the morphology of the silk fibroin scaffolds were investigated by HR-TEM. Magnetic nanoparticles were distributed within scaffolds structure. Biomineralization of hydroxyapatite on silk fibroin scaffolds with and without magnetic nanoparticles was investigated by an alternate soaking process. SEM images showed that the magnetic scaffolds were covered in an almost continuously film, which has a phase with nanostructured characteristics. This phase, which has as main components Ca and P, is made of lamellar formations. The design of an original magnetic 3D cell culture setup allowed us to observe cellular modifications under the exposure to magnetic field in the presence of magnetic silk fibroin biomaterials. The cellular proliferation potential of 3T3-E1 cell line was found increased under the magnetic field, especially in the presence of the magnetite nanoparticles. In addition, we showed that the low static magnetic field positively impacts on the osteogenic differentiation potential of the cells inside the biomimetic magnetic scaffolds. 10.1016/j.msec.2020.110714
    Engineering magnetically responsive tropoelastin spongy-like hydrogels for soft tissue regeneration. Pesqueira Tamagno,Costa-Almeida Raquel,Mithieux Suzanne M,Babo Pedro S,Franco Albina R,Mendes Bárbara B,Domingues Rui M A,Freitas Paulo,Reis Rui L,Gomes Manuela E,Weiss Anthony S Journal of materials chemistry. B Magnetic biomaterials are a key focus in medical research. Tropoelastin is the soluble precursor of elastin and is a critical component of tissues requiring elasticity as part of their physiological function. By utilising the versatility of tropoelastin and the ability to tailor its properties, we developed a novel magnetic spongy-like hydrogel based on tropoelastin doped with magnetic properties by in situ precipitation method. The presence of magnetic nanoparticles altered the secondary structure of tropoelastin. Bioengineered tropoelastin-based magnetic spongy-like hydrogels displayed a homogenous distribution of magnetic nanoparticles throughout the tropoelastin network and quick magnetic responsiveness to an applied external magnetic field. Morphologically, in the presence of magnetic nanoparticles, hydrated tropoelastin spongy-like hydrogels showed apparently smaller pore sizes and less swelling. Furthermore, in vitro biological studies using human tendon-derived cells revealed that magnetically responsive tropoelastin spongy-like hydrogels supported cell viability and enabled cell adhesion, spreading and migration into the interior of the spongy-like hydrogel up to two weeks. The bioengineered tropoelastin-based magnetic spongy-like hydrogel represents a novel class of hybrid biomaterial that can serve as a platform for soft tissue regeneration. 10.1039/c7tb02035j
    Integration of a Superparamagnetic Scaffold and Magnetic Field To Enhance the Wound-Healing Phenotype of Fibroblasts. Hao Suisui,Zhang Yu,Meng Jie,Liu Jian,Wen Tao,Gu Ning,Xu Haiyan ACS applied materials & interfaces Most of the existing scaffolds for guiding tissue regeneration do not provide direct mechanical stimulation to the cells grown on them. In this work, we used nanofibrous superparamagnetic scaffolds with applied magnetic fields to build a "dynamic" scaffold platform and investigated the modulating effects of this platform on the phenotypes of fibroblasts. The results of enzyme-linked immunosorbent and transwell assays indicated that fibroblasts cultivated in this platform secreted significantly higher type I collagen, vascular endothelial growth factor A, and transforming growth factor-β1 and did so in a time-dependent manner. At the same time, they produced fewer pro-inflammatory cytokines, including interleukin-1β and monocyte chemoattractant protein-1; this, in turn, accelerated the osteogenesis of preosteoblasts with the help of increased basic fibroblast growth factor as well as balanced extracellular matrix components. Mechanistic studies revealed that the platform modulated the phenotypic polarization of fibroblasts through the activation of components of integrin, focal adhesion kinase, and extracellular signal-regulated kinase signaling pathways and the inhibition of the activation of Toll-like receptor-4 and nuclear factor κB. Overall, the platform promoted the wound-healing phenotype of fibroblasts, which would be of great benefit to the scaffold-guided tissue regeneration. 10.1021/acsami.8b04149
    Magnetic double-network hydrogels for tissue hyperthermia and drug release. Tang Jingda,Qiao Yancheng,Chu Yanhui,Tong Zongfei,Zhou Yifan,Zhang Wenlei,Xie Shejuan,Hu Jian,Wang Tiejun Journal of materials chemistry. B Magnetic-field driven soft materials have found extensive applications in fields such as soft robotics, shape morphing and biomedicine. Compared to magnetoactive elastomers (MAEs), magnetic hydrogels have shown significant advantages for in vivo applications, because of their better biocompatibility, as well as their soft and wet nature. However, the poor mechanical properties and ion sensitivity of conventional magnetic hydrogels will severely limit their applications especially under physiological conditions. Double network hydrogels are tough and stable, but do not respond to environmental stimuli. Here magnetic double network (M-DN) hydrogels have been developed with outstanding mechanical performances and ion-resistant stability. M-DN hydrogels show a high modulus of ∼0.4 MPa and a high toughness of ∼1500 J m. The volume, magnetic and mechanical properties of M-DN hydrogels show negligible deterioration in ionic solutions. M-DN hydrogels exhibit magnetic responsiveness and have been used for tissue hyperthermia and drug release by magnetic induction heating. The induction heating behavior of M-DN hydrogels can be tuned to meet the clinical requirements, by changing the magnetic field strength or the composition of magnetic hydrogels. M-DN hydrogels may be inspiring to the development of responsive DN hydrogels and expand their more potential applications in load-bearing biomedical engineering. 10.1039/c8tb03301c
    Super-Elastic Magnetic Structural Color Hydrogels. Zhang Yalan,Wang Yu,Wang Huan,Yu Ying,Zhong Qifeng,Zhao Yuanjin Small (Weinheim an der Bergstrasse, Germany) Structural color hydrogels are promising candidates as scaffold materials for tissue engineering and for matrix cell culture and manipulation, while their super-elastic features are still lacking due to the irreconcilable interfere of the precursor and the self-assembly unit. This hinders many of their practical biomedical applications where elasticity is required. Herein, hydrophilic and size-controllable Fe O @poly(4-styrenesulfonic acid-co-maleic acid) (PSSMA)@SiO magnetic response photonic crystals are fabricated as the assembly units of the structural color hydrogels by orderly packing of core-shell colloidal nanocrystal clusters via a two-step facile synthesis approach. These units are capable of responding instantaneously to an external magnetic field with resistance to interference of ions, thus, by integrating super-elastic hydrogels, super-elastic magnetic structural color hydrogels can be achieved. The structural color arises from the dynamic ordering of the magnetic nanoparticles through the contactless control of external magnetic field, allowing regional polymerization of hydrogels via changing orientation and strength of external magnetic field. These regionally polymerized super-elastic magnetic structural color hydrogels can work as anti-counterfeiting labels with super-elastic identification, which may be widely used in the future. 10.1002/smll.201902198
    Biocompatible FeO/chitosan scaffolds with high magnetism. Ge Jianhua,Zhai Mengdi,Zhang Yi,Bian Jie,Wu Junling International journal of biological macromolecules Durable and biocompatible magnetic scaffolds prepared by simple approaches are important for the development of tissue engineering. In this work, by freeze-drying method and without using any crosslinker, we successfully fabricated FeO/chitosan magnetic scaffolds that belong to hard magnetic materials and are stable in physiological fluid. In vitro biocompatibility assay showed that mouse mesenchymal progenitor cells grow normally on the surface of the scaffolds. So these magnetic scaffolds have potentials to be used in tissue engineering as implants that independently direct drug targeting. 10.1016/j.ijbiomac.2019.01.077
    Magnetic nanocomposite hydrogels and static magnetic field stimulate the osteoblastic and vasculogenic profile of adipose-derived cells. Filippi Miriam,Dasen Boris,Guerrero Julien,Garello Francesca,Isu Giuseppe,Born Gordian,Ehrbar Martin,Martin Ivan,Scherberich Arnaud Biomaterials Exposure of cells to externally applied magnetic fields or to scaffolding materials with intrinsic magnetic properties (magnetic actuation) can regulate several biological responses. Here, we generated novel magnetized nanocomposite hydrogels by incorporation of magnetic nanoparticles (MNPs) into polyethylene glycol (PEG)-based hydrogels containing cells from the stromal vascular fraction (SVF) of human adipose tissue. We then investigated the effects of an external Static Magnetic Field (SMF) on the stimulation of osteoblastic and vasculogenic properties of the constructs, with MNPs or SMF alone used as controls. MNPs migrated freely through and out of the material following the magnetic gradient. Magnetically actuated cells displayed increased metabolic activity. After 1 week, the enzymatic activity of Alkaline Phosphatase (ALP), the expression of osteogenic markers (Runx2, Collagen I, Osterix), and the mineralized matrix deposition were all augmented as compared to controls. With magnetic actuation, strong activation of endothelial, pericytic and perivascular genes paralleled increased levels of VEGF and an enrichment in the CD31 cells population. The stimulation of signaling pathways involved in the mechanotransduction, like MAPK8 or Erk, at gene and protein levels suggested an effect mediated through the mechanical stimulation. Upon subcutaneous implantation in mice, magnetically actuated constructs exhibited denser, more mineralized and faster vascularized tissues, as revealed by histological and micro-computed tomographic analyses. The present study suggests that magnetic actuation can stimulate both the osteoblastic and vasculogenic potentials of engineered bone tissue grafts, likely at least partially by mechanically stimulating the function of progenitor cells. 10.1016/j.biomaterials.2019.119468
    An Anisotropic Hydrogel Based on Mussel-Inspired Conductive Ferrofluid Composed of Electromagnetic Nanohybrids. Liu Kezhi,Han Lu,Tang Pengfei,Yang Kaiming,Gan Donglin,Wang Xiao,Wang Kefeng,Ren Fuzeng,Fang Liming,Xu Yonggang,Lu Zhifeng,Lu Xiong Nano letters Anisotropic hydrogels with a hierarchical structure can mimic biological tissues, such as neurons or muscles that show directional functions, which are important factors for signal transduction and cell guidance. Here, we report a mussel-inspired approach to fabricate an anisotropic hydrogel based on a conductive ferrofluid. First, polydopamine (PDA) was used to mediate the formation of PDA-chelated carbon nanotube-FeO (PFeCNT) nanohybrids and also used as a dispersion medium to stabilize the nanohybrids to form a conductive ferrofluid. The ferrofluid can respond to an orientated magnetic field and be programed to form aligned structures, which were then frozen in a hydrogel network formed via free-radical polymerization and gelation. The resulted hydrogel shows directional conductive and mechanical properties, mimicking an oriented biological tissue. Under external electrical stimulation, the orientated PFeCNT nanohybrids can be sensed by the myoblasts cultured on the hydrogel, resulting in the oriented growth of cells. In summary, the mussel-inspired anisotropic hydrogel with its aligned structural complexity and anisotropic properties together with the cell affinity and tissue adhesiveness is a potent multifunctional biomaterial for mimicking oriented tissues to guide cell proliferation and tissue regeneration. 10.1021/acs.nanolett.9b00363
    Imparting Functionality to the Hydrogel by Magnetic-Field-Induced Nano-assembly and Macro-response. Shi Wei,Huang Jin,Fang Ruochen,Liu Mingjie ACS applied materials & interfaces Hydrogels are composed of 3D hydrophilic networks with an abundance of water; they are analogous to biological soft tissues. Their unique physico-chemical properties endow hydrogels with great potential in many fields, including tissue engineering and flexible sensing. However, inadequate functionality, such as lack of rapid responsiveness, severely limits practical applications in many areas. Therefore, imparting functionality to the hydrogel is a hot research topic. The magnetic field, as an important physical field, provides a new strategy with a variety of advantages. Magnetic-field-induced ordered nano-assembly brought anisotropic properties and novel performance. Furthermore, the magnetic responsiveness of hydrogels with magnetic nanoparticles can lead to the generation of functionality under magnetic fields. Thus, we aim to systematically describe the significant effect of magnetic fields on the functionality of the hydrogel. In this review, magnetic-field-induced assembly of nanomaterials with different dimensions and resulting functional performance are introduced. The functionalities of hydrogels based on magnetic-field-induced macroscopic responses are also summarized. We believe this review will motivate more exploration of the application of magnetic fields to develop functional hydrogel materials. 10.1021/acsami.9b16770
    Bioinspired Three-Dimensional Magnetoactive Scaffolds for Bone Tissue Engineering. Fernandes Margarida M,Correia Daniela M,Ribeiro Clarisse,Castro Nelson,Correia Vitor,Lanceros-Mendez Senentxu ACS applied materials & interfaces Bone tissue repair strategies are gaining increasing relevance due to the growing incidence of bone disorders worldwide. Biochemical stimulation is the most commonly used strategy for cell regeneration, while the application of physical cues, including magnetic, mechanical, or electrical fields, is a promising, however, scarcely investigated field. This work reports on novel magnetoactive three-dimensional (3D) porous scaffolds suitable for effective proliferation of osteoblasts in a biomimetic microenvironment. This physically active microenvironment is developed through the bone-mimicking structure of the scaffold combined with the physical stimuli provided by a magnetic custom-made bioreactor on a magnetoresponsive scaffold. Scaffolds are obtained through the development of nanocomposites comprised of a piezoelectric polymer, poly(vinylidene fluoride) (PVDF), and magnetostrictive particles of CoFeO, using a solvent casting method guided by the overlapping of nylon template structures with three different fiber diameter sizes (60, 80, and 120 μm), thus generating 3D scaffolds with different pore sizes. The magnetoactive composites show a structure very similar to trabecular bone with pore sizes that range from 5 to 20 μm, owing to the inherent process of crystallization of PVDF with the nanoparticles (NPs), interconnected with bigger pores, formed after removing the nylon templates. It is found that the materials crystallize in the electroactive β-phase of PVDF and promote the proliferation of preosteoblasts through the application of magnetic stimuli. This phenomenon is attributed to both local magnetomechanical and magnetoelectric response of the scaffolds, which induce a proper cellular mechano- and electro-transduction process. 10.1021/acsami.9b14001
    A magnetically responsive nanocomposite scaffold combined with Schwann cells promotes sciatic nerve regeneration upon exposure to magnetic field. Liu Zhongyang,Zhu Shu,Liu Liang,Ge Jun,Huang Liangliang,Sun Zhen,Zeng Wen,Huang Jinghui,Luo Zhuojing International journal of nanomedicine Peripheral nerve repair is still challenging for surgeons. Autologous nerve transplantation is the acknowledged therapy; however, its application is limited by the scarcity of available donor nerves, donor area morbidity, and neuroma formation. Biomaterials for engineering artificial nerves, particularly materials combined with supportive cells, display remarkable promising prospects. Schwann cells (SCs) are the absorbing seeding cells in peripheral nerve engineering repair; however, the attenuated biologic activity restricts their application. In this study, a magnetic nanocomposite scaffold fabricated from magnetic nanoparticles and a biodegradable chitosan-glycerophosphate polymer was made. Its structure was evaluated and characterized. The combined effects of magnetic scaffold (MG) with an applied magnetic field (MF) on the viability of SCs and peripheral nerve injury repair were investigated. The magnetic nanocomposite scaffold showed tunable magnetization and degradation rate. The MGs synergized with the applied MF to enhance the viability of SCs after transplantation. Furthermore, nerve regeneration and functional recovery were promoted by the synergism of SCs-loaded MGs and MF. Based on the current findings, the combined application of MGs and SCs with applied MF is a promising therapy for the engineering of peripheral nerve regeneration. 10.2147/IJN.S144715
    Tissue-engineered magnetic cell sheet patches for advanced strategies in tendon regeneration. Gonçalves Ana I,Rodrigues Márcia T,Gomes Manuela E Acta biomaterialia Tendons are powerful 3D biomechanically structures combining a few cells in an intrincated and highly hierarchical niche environment. When tendon homeostasis is compromised, restoration of functionality upon injury is limited and requires alternatives to current augmentation or replacement strategies. Cell sheet technologies are a powerful tool for the fabrication of living extracellular-rich patches towards regeneration of tenotopic defects. Thus, we originally propose the development of magnetically responsive tenogenic patches through magnetic cell sheet (magCSs) technology that enable the remote control upon implantation of the tendon-mimicking constructs. A Tenomodulin positive (TNMD) subpopulation of cells sorted from a crude population of human adipose stem cells (hASCs) previously identified as being prone to tenogenesis was selected for the magCSs patch construction. We investigated the stability, the cellular co-location of the iron oxide nanoparticles (MNPs), as well as the morphology and mechanical properties of the developed magCSs. Moreover, the expression of tendon markers and collagenous tendon-like matrix were further assessed under the actuation of an external magnetic field. Overall, this study confirms the potential to bioengineer tendon patches using a magnetic cell sheet construction with magnetic responsiveness, good mechanoelastic properties and a tenogenic prone stem cell population envisioning cell-based functional therapies towards tendon regeneration. STATEMENT OF SIGNIFICANCE:The concept of magnetic force-based tissue engineering may assist the development of innovative solutions to treat tendon (or other tissues) disorders upon remote control of biological processes as cell migration or differentiation. Herein, we originally fabricated magnetic responsive cell sheets (magCSs) with a Tenomodulin positive subpopulation of adipose tissue derived stem cells identified to commit to the tenogenic lineage. To the best of authors knowledge, this is the first time a tendon oriented strategy resorting on magCSsis reported. Moreover, the promising role of tenogenic living constructs fabricated as magnetically responsive ECM-rich patches is highlighted, envisioning the stimulation of endogenous regenerative mechanisms. Altogether, these findings contribute to future stem cell studies and their translation toward tendon therapies. 10.1016/j.actbio.2017.09.014
    Magnetic nanoparticles modified-porous scaffolds for bone regeneration and photothermal therapy against tumors. Lu Jia-Wei,Yang Fan,Ke Qin-Fei,Xie Xue-Tao,Guo Ya-Ping Nanomedicine : nanotechnology, biology, and medicine For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFeO nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the SrFeO nanoparticles in MBCS improved the photothermal conversion property. Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the multifunctional MBCS with excellent bone regeneration and photothermal therapy functions has a great application for treating the tumor-related bone defects. 10.1016/j.nano.2017.12.025
    Nanostructured magnetic MgSiO-CoFeO composite scaffold with multiple capabilities for bone tissue regeneration. Bigham Ashkan,Aghajanian Amir Hamed,Behzadzadeh Shima,Sokhani Zahra,Shojaei Sara,Kaviani Yeganeh,Hassanzadeh-Tabrizi S A Materials science & engineering. C, Materials for biological applications Multifunctional magnetic 3D scaffolds are recently of particular interest because of their applications in hyperthermia-based therapy and localized drug delivery beside of their basic properties to be applied in bone tissue regeneration. In the current study, a magnetic nanocomposite is designed and synthesized through a two-step synthesis strategy in which CoFeO nanoparticles are prepared via sol-gel combustion method and then they are coated through sol-gel method with MgSiO. The characterization relates to the nanocomposite shows that MgSiO-CoFeO is successfully synthesized and it has a core-shell structure. Then, 3D scaffolds are fabricated through polymer sponge technique from the nanocomposite. Physiochemical and biological properties of the scaffolds are assessed in vitro amongst which bioactivity, biodegradability, mechanical properties, hyperthermia capability, controlled release potential, antibacterial activity, cell compatibility and attachment can be mentioned. The results demonstrate that the scaffolds have high porous structure with interconnected porosity and desirable mechanical properties close to cancellous bone. The magnetic scaffold is biodegradable and bioactive and exhibits controlled release of rifampin as an antibiotic drug up to 96 h. Moreover, in the exposure of different magnetic fields it has potential to produce heat for different kinds of hyperthermia-based therapies. The antibacterial activity of drug-loaded scaffold is assessed against S. aureus bacteria. The results suggest that MgSiO-CoFeO nanocomposite scaffold with multiple capabilities has a great potential to be applied in the case of large bone defects which are caused by tumors to not only eradicate remained cancerous tissues, but also prevent infection after surgery and regenerate bone defect. 10.1016/j.msec.2019.01.096
    Core-shell magnetic bimetallic MOF material for synergistic enrichment of phosphopeptides. Cao Licheng,Zhao Yameng,Chu Zhanying,Zhang Xiangmin,Zhang Weibing Talanta In proteomics, phosphorylation is an important process for protein post-translational modification (PTM), which greatly improves the diversity of proteomes. The PTM regulates almost all physiological and pathological processes such as signal transduction, cell division, proliferation, differentiation and metabolism. The abnormal expression of protein phosphorylation is also associated with cellular metabolic disorders and a range of diseases. However, in mass spectrometry-based phosphorylated peptideomics studies, phosphorylated peptide signals were inhibited by a high abundance of non-phosphorylated peptides; thus, highly selective enrichment was required. In this study, a newly designed material named FeO@MIL(Fe/Ti) was synthesized using a layer-by-layer self-assembly technique that coats the surface of magnetic oxide nanospheres with bimetallic MOF of iron and titanium. The synergistic synthetic coating of the bimetallic MOF gives the material a large surface area and excellent hydrophilicity, which endow the nanoparticles with excellent phosphopeptide enrichment ability, high selectivity (β-casein/BSA molar ratio 1:500), a low detection limit (3 fmol), high recovery rate (85%), strong binding capacity, size exclusion ability, and ideal batch-to-batch repeatability. For comparison, we used FeO@MIL(Fe/Ti) and two single-metal MOF materials FeO@MIL-100(Fe) and FeO@MIL-125(Ti), to enrich α-casein in the middle. Thus, the iron-titanium bimetallic MOF can not only enrich all the phosphorylated peptides enriched by FeO@MIL-100(Fe) and FeO@MIL-125(Ti), but can also specifically enrich four phosphorylated peptides. Encouraged by the excellent results of characterization and standard protein enrichment, we used this material to analyze human serum and found that bimetallic materials can effectively enrich all four phosphorylated peptides and exclude high molecular proteins. These experimental results indicate that the novel bimetallic MOF is a good candidate to analyze protein phosphorylation in complex samples. 10.1016/j.talanta.2019.120165
    Ag-doped magnetic metal organic framework as a novel nanostructured material for highly efficient antibacterial activity. Rahmati Ziba,Abdi Jafar,Vossoughi Manouchehr,Alemzadeh Iran Environmental research In the last decades, numerous attempts have been made to prevent microbial pollution spreading, using antibacterial agents. Zeolitic imidazolate framework-8 (ZIF-8) belongs to a subgroup of metal organic frameworks (MOFs) merits of attention due to the zinc ion clusters and its effective antibacterial activity. In this work, Ag-doped magnetic microporous γ-FeO@SiO@ZIF-8-Ag (FSZ-Ag) was successfully synthesized by a facile methodology in room temperature and used as an antibacterial agent against the growth of the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria. Several characterization methods were applied to analyze the properties of the materials, and the results confirmed the accuracy of the synthesis procedure. Silver ions have employed to enhance the efficiency of antibacterial activity. As the results illustrated, FSZ-Ag nanostructured material had superior performance to inactive E. coli and S. aureus in growth inhibition test in liquid media. The best antibacterial activity as minimum inhibitory concentration (MIC) was 100 mg/L of FSZ-Ag against both bacteria. Leaching rates of silver ions showed that 80% of Ag released in the solutions, which was responsible for inhibiting the growth of bacteria. Also, fluorescence microscopy was used to investigate bacterial viability after 20 h contacting FSZ-Ag to distinguish live and dead bacteria by staining with DAPI and PI fluorescence stains. This novel magnetic nanostructured material is an excellent promising candidate to use in biological applications as high potential bactericidal materials. 10.1016/j.envres.2020.109555
    Magnetic field and nano-scaffolds with stem cells to enhance bone regeneration. Xia Yang,Sun Jianfei,Zhao Liang,Zhang Feimin,Liang Xing-Jie,Guo Yu,Weir Michael D,Reynolds Mark A,Gu Ning,Xu Hockin H K Biomaterials Novel strategies utilizing magnetic nanoparticles (MNPs) and magnetic fields are being developed to enhance bone tissue engineering efficacy. This article first reviewed cutting-edge research on the osteogenic enhancements via magnetic fields and MNPs. Then the current developments in magnetic strategies to improve the cells, scaffolds and growth factor deliveries were described. The magnetic-cell strategies included cell labeling, targeting, patterning, and gene modifications. MNPs were incorporated to fabricate magnetic composite scaffolds, as well as to construct delivery systems for growth factors, drugs and gene transfections. The novel methods using magnetic nanoparticles and scaffolds with magnetic fields and stem cells increased the osteogenic differentiation, angiogenesis and bone regeneration by 2-3 folds over those of the controls. The mechanisms of magnetic nanoparticles and scaffolds with magnetic fields and stem cells to enhance bone regeneration were identified as involving the activation of signaling pathways including MAPK, integrin, BMP and NF-κB. Potential clinical applications of magnetic nanoparticles and scaffolds with magnetic fields and stem cells include dental, craniofacial and orthopedic treatments with substantially increased bone repair and regeneration efficacy. 10.1016/j.biomaterials.2018.08.040
    Multi-layer pre-vascularized magnetic cell sheets for bone regeneration. Silva Ana S,Santos Lúcia F,Mendes Maria C,Mano João F Biomaterials The lack of effective strategies to produce vascularized 3D bone transplants in vitro, hampers the development of thick-constructed bone, limiting the translational of lab-based engineered system to clinical practices. Cell sheet (CS) engineering techniques provide an excellent microenvironment for vascularization since the technique can maintain the intact cell matrix, crucial for angiogenesis. In an attempt to develop hierarchical vascularized 3D cellular constructs, we herein propose the construction of stratified magnetic responsive heterotypic CSs by making use of iron oxide nanoparticles previously internalized within cells. Magnetic force-based CS engineering allows for the construction of thick cellular multilayers. Results show that osteogenesis is achieved due to a synergic effect of human umbilical vein endothelial cells (HUVECs) and adipose-derived stromal cells (ASCs), even in the absence of osteogenic differentiating factors. Increased ALP activity, matrix mineralization, osteopontin and osteocalcin detection were achieved over a period of 21 days for the heterotypic CS conformation (ASCs/HUVECs/ASCs), over the homotypic one (ASCs/ASCs), corroborating our findings. Moreover, the validated crosstalk between BMP-2 and VEGF releases triggers not only the recruitment of blood vessels, as demonstrated in an in vivo CAM assay, as well as the osteogenesis of the 3D cell construct. The in vivo angiogenic profile also demonstrated preserved human vascular structures and human cells showed the ability to migrate and integrate within the chick vasculature. 10.1016/j.biomaterials.2019.119664
    Regeneration of large bone defects using mesoporous silica coated magnetic nanoparticles during distraction osteogenesis. Jia Yachao,Zhang Pengli,Sun Yunchu,Kang Qinglin,Xu Jia,Zhang Chunfu,Chai Yimin Nanomedicine : nanotechnology, biology, and medicine Distraction osteogenesis (DO) represents an effective but undesirably lengthy treatment for large bone defects. Both magnetic nanoparticles and silicon have been shown to induce osteogenic differentiation of mesenchymal stem cells (MSCs), the key participant in bone regeneration. We herein synthesized mesoporous silica coated magnetic (FeO) nanoparticles (M-MSNs) and evaluated its potential for acceleration of bone regeneration in a rat DO model. The M-MSNs exhibited good biocompatibility and remarkable capability in promoting the osteogenic differentiation of MSCs via the canonical Wnt/β-catenin pathway in vitro. More importantly, local injection of M-MSNs dramatically accelerated bone regeneration in a rat DO model according to the results of X-ray imaging, micro-CT, mechanical testing, histological examination, and immunochemical analysis. This study demonstrates the notable potential of M-MSNs in promoting bone regeneration during DO by enhancing the osteogenic differentiation of MSCs, paving the way for clinical translation of M-MSNs in DO to repair large bone defects. 10.1016/j.nano.2019.102040
    Magnetic lanthanum-doped hydroxyapatite/chitosan scaffolds with endogenous stem cell-recruiting and immunomodulatory properties for bone regeneration. Wang Qiyang,Tang Yaqi,Ke Qinfei,Yin Wenjing,Zhang Changqing,Guo Yaping,Guan Junjie Journal of materials chemistry. B Generally, the addition of exogenous stem cells and host-to-scaffold immune responses restricts the clinical applications of hydroxyapatite (HA)/chitosan (CS) scaffolds for bone regeneration. To achieve "facilitated endogenous tissue engineering", magnetic M-type hexagonal ferrite (SrFe12O19) nanoparticles were incorporated into bone scaffolds to recruit endogenous stem cells. Then, lanthanum incorporation was utilized to regulate host-to-scaffold immune responses and to provide a pro-regenerative environment for recruited endogenous stem cells. Here, we first fabricated and characterized magnetic lanthanum-doped HA/CS scaffolds. The MLaHA/CS scaffolds were demonstrated to be effective at recruiting rat bone marrow mesenchymal stem cells (rBMSCs) and modulating host-to-scaffold immune responses by promoting macrophage polarization into the anti-inflammatory phenotype (M2) in vitro. By further examining the underlying mechanism, we found that MLaHA/CS scaffolds could promote the osteogenic differentiation of rBMSCs by upregulating the phosphorylation of the Smad 1/5/9 pathway. When MLaHA/CS scaffolds were implanted into rat calvarial defects, the incorporation of magnetic nanoparticles and lanthanum significantly promoted the new bone regeneration, as revealed by micro-CT assays and histological staining. Our findings suggest that MLaHA/CS shows great potential for use as a cell-free and biocompatible scaffold for bone regeneration. 10.1039/d0tb00342e
    Biocompatible Injectable Magnetic Hydrogel Formed by Dynamic Coordination Network. Shi Liyang,Zeng Yuqin,Zhao Yannan,Yang Bin,Ossipov Dmitri,Tai Cheuk-Wai,Dai Jianwu,Xu Changgang ACS applied materials & interfaces Magnetic hydrogel that can respond to a magnetic stimulus is a promising biomaterial for tissue regeneration and cancer treatment. In this study, a novel magnetic hydrogel is formed by simply mixing bisphosphonate (BP)-modified hyaluronic acid (i.e., HA-BP) polymeric solution and iron oxide (FeO) nanoparticle dispersion, in which the hydrogel networks are cross-linked by BP groups and iron atoms on the surface of particle. The iron-BP coordination chemistry affords a dynamic network, characterized by self-healing, shear-thinning, and smoothly injectable properties. Moreover, the HA-BP·FeO magnetic hydrogel demonstrates heat-generation characterization under an alternating magnetic field. The animal experiments confirm the biocompatibilities of HA-BP·FeO hydrogel, which presents the hydrogels potential for tissue regeneration and anticancer treatment applications. 10.1021/acsami.9b17627