Magnetic Scaffolds Research Articles

Spatiotemporal Magnetocaloric Microenvironment for Guiding the Fate of Biodegradable Polymer Implants

AbstractThe degradation behavior of implants is significantly important for bone repair. However, it is still unprocurable to spatiotemporally regulate the degradation of the implants to match bone ingrowth. In this paper, a magneto‐controlled biodegradation model is established to explore the degradation behavior of magnetic scaffolds in a magnetothermal microenvironment generated by an alternating magnetic field (AMF). The results demonstrate that the scaffolds can be heated by magnetic nanoparticles (NPs) under AMF, which dramatically accelerated scaffold degradation. Especially, magnetic NPs modified by oleic acid with a better interface compatibility exhibit a greater heating efficiency to further facilitate the degradation. Furthermore, the molecular dynamics simulations reveal that the enhanced motion correlation between magnetic NPs and polymer matrix can accelerate the energy transfer. As a proof‐of‐concept, the feasibility of magneto‐controlled degradation for implants is demonstrated, and an optimizing strategy for better heating efficiency of nanomaterials is provided, which may have great instructive significance for clinical medicine.

A Multiphysics Model for Bone Repair Using Magnetic Scaffolds for Targeted Drug Delivery

Magnetic bone substitutes are multifunctional nanocomposite biomaterials designed to serve as an in situ attraction platform for magnetic carriers of growth factors. The morphological and functional properties of these biomaterials were characterized so far, but very little is known on the treatment dynamics, and the latter cannot be designed from an engineering point of view. For the first time, this work deals with the mathematical modeling of the use of magnetic scaffolds and functionalized nanoparticles to evaluate the enhancement of osteogenesis and bone repair. The non-linear magnetization of the scaffolds is considered to simulate the attraction and transport of magnetic nanoparticles. Different biomaterials and drug carriers from the literature are analyzed. The drug release via RF-heating is modeled considering the multiphysics nature of the phenomena. The physiological process of bone healing is reproduced using nine non-linear equations. The influence of the delivered growth factor on osteogenesis is assessed and quantified in silico, while compared to numerical simulations of intravenous injection of growth factor and to its release from the biomaterial.The exploitation of magnetic carriers of biomolecules with magnetic scaffolds allows to produce a more homogeneous and uniform distribution of mature bone, overcoming the limitation of traditional drug delivery techniques

Magnetic and radio-labeled bio-hybrid scaffolds to promote and track in vivo the progress of bone regeneration.

This work describes the preparation, characterization and functionalization with magnetic nanoparticles of a bone tissue-mimetic scaffold composed of collagen and hydroxyapatite obtained through a biomineralization process. Bone remodeling takes place over several weeks and the possibility to follow it in vivo in a quick and reliable way is still an outstanding issue. Therefore, this work aims to produce an implantable material that can be followed in vivo during bone regeneration by using the existing non-invasive imaging techniques (MRI). To this aim, suitably designed biocompatible SPIONs were linked to the hybrid scaffold using two different strategies, one involving naked SPIONs (nMNPs) and the other using coated and activated SPIONs (MNPs) exposing carboxylic acid functions allowing a covalent attachment between MNPs and collagen molecules. Physico-chemical characterization was carried out to investigate the morphology, crystallinity and stability of the functionalized materials followed by MRI analyses and evaluation of a radiotracer uptake ([99mTc]Tc-MDP). Cell proliferation assays in vitro were carried out to check the cytotoxicity and demonstrated no side effects due to the SPIONs. The achieved results demonstrated that the naked and coated SPIONs are more homogeneously distributed in the scaffold when incorporated during the synthesis process. This work demonstrated a suitable approach to develop a biomaterial for bone regeneration that allows the monitoring of the healing progress even for long-term follow-up studies.

Development and characterisation of microporous biomimetic scaffolds loaded with magnetic nanoparticles as bone repairing material

Fine-tuning of the scaffolds structural features for bone tissue engineering can be an efficient approach to regulate the specific response of the osteoblasts. Here, we loaded magnetic nanoparticles aka superparamagnetic iron oxide nanoparticles (SPIONs) into 3D composite scaffolds based on biological macromolecules (chitosan, collagen, hyaluronic acid) and calcium phosphates for potential applications in bone regeneration, using a biomimetic approach. We assessed the effects of organic (chitosan/collagen/hyaluronic acid) and inorganic (calcium phosphates, SPIONs) phase over the final features of the magnetic scaffolds (MS). Mechanical properties, magnetic susceptibility and biological fluids retention are strongly dependent on the final composition of MS and within the recommended range for application in bone regeneration. The MS architecture/pore size can be made bespoken through changes of the final organic/inorganic ratio. The scaffolds undertake mild degradation as the presence of inorganic components hinders the enzyme catalytic activity. In vitro studies indicated that osteoblasts (SaOS-2) on MS9 had similar cell behaviour activity in comparison with the TCP control. In vivo data showed an evident development of integration and resorption of the MS composites with low inflammation activity. Current findings suggest that the combination of SPIONs into 3D composite scaffolds can be a promising toolkit for bone regeneration.

Rational Synthesis of Aptamer-Functionalized Polyethylenimine-Modified Magnetic Graphene Oxide Composites for Highly Efficient Enrichment and Comprehensive Metabolomics Analysis of Exosomes.

Exosomes, which are phospholipid bilayer nanovesicles, can transfer their content to recipient cells, playing a crucial role in intercellular communication. Exosomes have emerged as promising cancer biomarkers. However, a convenient, efficient, and economical approach for their isolation and comprehensive analysis is still technically challenging. In this study, aptamer-based immunoaffinitive magnetic composites, MagG@PEI@DSP@aptamer, were prepared to achieve the convenient capture, efficient enrichment, and mild release of exosomes. The constructed composites contain three segments: a PEI-modified magnetic graphene scaffold, an aptamer CD63 sequence, and a cleavable cross-linker in between. Notably, the binding capacity of MagG@PEI@DSP for an aptamer is 93 nmol/mg, and per milligram MagG@PEI@DSP@aptamer could capture 450 μg exosomes. Moreover, the released exosomes from MagG@PEI@DSP@aptamer composites were intact and well-dispersed. The prepared composites were then applied to profile the metabolite composition of exosomes secreted by breast cancer cells MCF-7, and the number of detected features was obviously increased when compared to that obtained by the traditional ultracentrifugation method (4528 vs 3710 and 3967 vs 3785 in the positive and negative ionization modes). Besides, the exosomes secreted by MCF-7 and normal breast cells MCF-10A were isolated from cell culture medium with MagG@PEI@DSP@aptamer, and their metabolic profiles were then comprehensively analyzed; in total, 119 metabolites in MCF-7 and MCF-10A were identified. Compared with exosomes from MCF-10A, 43 and 42 metabolites were upregulated and downregulated, respectively, in those from MCF-7. These data showed that the prepared MagG@PEI@DSP@aptamer composites can be used to effectively capture exosomes and further for metabolomics analysis.

Micro Magnetic Field Produced by Fe3O4 Nanoparticles in Bone Scaffold for Enhancing Cellular Activity

The low cellular activity of poly-l-lactic acid (PLLA) limits its application in bone scaffold, although PLLA has advantages in terms of good biocompatibility and easy processing. In this study, superparamagnetic Fe3O4 nanoparticles were incorporated into the PLLA bone scaffold prepared by selective laser sintering (SLS) for continuously and steadily enhancing cellular activity. In the scaffold, each Fe3O4 nanoparticle was a single magnetic domain without a domain wall, providing a micro-magnetic source to generate a tiny magnetic field, thereby continuously and steadily generating magnetic stimulation to cells. The results showed that the magnetic scaffold exhibited superparamagnetism and its saturation magnetization reached a maximum value of 6.1 emu/g. It promoted the attachment, diffusion, and interaction of MG63 cells, and increased the activity of alkaline phosphatase, thus promoting the cell proliferation and differentiation. Meanwhile, the scaffold with 7% Fe3O4 presented increased compressive strength, modulus, and Vickers hardness by 63.4%, 78.9%, and 19.1% compared with the PLLA scaffold, respectively, due to the addition of Fe3O4 nanoparticles, which act as a nanoscale reinforcement in the polymer matrix. All these positive results suggested that the PLLA/Fe3O4 scaffold with good magnetic properties is of great potential for bone tissue engineering applications.

Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment

Injuries affecting load bearing tendon tissues are a significant clinical burden and efficient treatments are still unmet. Tackling tendon regeneration, tissue engineering strategies aim to develop functional substitutes that recreate native tendon milieu. Tendon mimetic scaffolds capable of remote magnetic responsiveness and functionalized magnetic nanoparticles (MNPs) targeting cellular mechanosensitive receptors are potential instructive tools to mediate mechanotransduction in guiding tenogenic responses. In this work, we combine magnetically responsive scaffolds and targeted Activin A type II receptor in human adipose stem cells (hASCs), under alternating magnetic field (AMF), to synergistically facilitate external control over signal transduction. The combination of remote triggering TGF-β/Smad2/3 using MNPs tagged hASCs, through magnetically actuated scaffolds, stimulates overall expression of tendon related genes and the deposition of tendon related proteins, in comparison to non-stimulated conditions. Moreover, the phosphorylation of Smad2/3 proteins and their nuclear co-localization was also more evident. Overall, biophysical stimuli resulting from magnetic scaffolds and magnetically triggered cells under AMF stimulation modulate the mechanosensing response of hASCs towards tenogenesis, holding therapeutic promise. Statement of SignificanceThe concept of magnetically-assisted tissue engineering may assist the development of innovative solutions to treat tendon disorders upon remote control of biological processes as cell migration or differentiation. Herein, we originally combine a fibrous aligned superparamagnetic scaffold, based on a biodegradable polymeric blend of starch and poly-ɛ-caprolactone incorporating magnetic nanoparticles (MNPs), and human adipose stem cells (hASCs) labelled with MNPs functionalized with anti-activin receptor type IIA (ActRIIA). Constructs were stimulated using alternating magnetic field (AMF), to activate the ActRIIA and subsequent induction of TGF-β signaling, through Smad2/3 phosphorylation cascade, enhancing the expression of tendon-related markers. Altogether, these findings contribute with powerful bio-magnetic approaches to activate key tenogenic pathways, envisioning future translation of magnetic biomaterials into regenerative platforms for tendon repair.

Fabrication and physicochemical characterization of a novel magnetic nanocomposite scaffold: Electromagnetic field effect on biological properties.

In the current research, a novel poly(ε-caprolactone) nanofibrous composite scaffold including CZF-NPs1 (cobalt‑zinc ferrite nanoparticles) was investigated to study the physical, mechanical and biological properties of new magnetic nanofibrous materials and then to evaluate the effect of applied electromagnetic field on biological properties of these scaffolds. It was observed that the incorporation of CZF-NPs up to 3wt.% leads to decrease in nanofibers' diameter to 466nm. By raising the content of CZF-NPs, hydrophilicity and biodegradation of magnetic nanofibrous scaffolds improved significantly. In addition, the mechanical properties of nanofibers such as stress at break point was interestingly increased in the sample with 3wt.% of CZF-NPs. The results of biocompatibility, cell adhesion and cell staining assays with L929 cells are much more improved in nanofibers embedded with CZF-NPs in the presence of external electromagnetic field (EMF). According to this study, magnetic nanofibrous scaffolds composed of PCL/CZF-NPs could be considered as a promising candidate to regenerate damaged tissues.

Osteogenic effects of inductive coupling magnetism from magnetic 3D printed hydrogel scaffold

The surface of iron oxide nanoparticles was chemically modified before being embedded in a chitosan hydrogel and for the first time, made into a scaffold by three-dimensional printing. The nanoparticles were embedded in the scaffold so that they would not be ingested by the surrounding tissue cells. The effects of the inductive coupling magnetism on bone cells were studied in the presence of an external magnetic force.Results from the FTIR and surface zeta potential analyses suggested that the citrate modification of the nanoparticles was successful. TEM images showed that the modification helped reduce the sizes of the agglomerates from 1237 nm to 408 nm. The negative charge on the particle surface formed ionic interaction with the chitosan in the solution. The smaller and charged particles evenly dispersed in a chitosan solution without blocking the extruding nozzle during three-dimensional printing.With the presence of the inductive coupling magnetism, osteoblast cells had a higher proliferation, type I collagen production, alkaline phosphatase expression, and mineralization (p < 0.01). The morphology of the osteoblast cells appeared normal and elongated. At the end of 21 days the cells proliferated into the interconnected pores as seen in the SEM images.Inductive coupling was shown to have invoked additional osteogenic responses in bone cells aside from the positive effects from the external magnetic force. The novel magnetic scaffold provided a potential alternative for bone tissue repair using magnetic therapy.

Magnetic resonance (MR) safety and compatibility of a novel iron bioresorbable scaffold

Fully bioresorbable scaffolds have been designed to overcome the limitations of traditional drug-eluting stents (DESs), which permanently cage the native vessel wall and pose possible complications. The ultrathin-strut designed sirolimus-eluting iron bioresorbable coronary scaffold system (IBS) shows comparable mechanical properties to traditional DESs and exhibits an adaptive degradation profile during target vessel healing, which makes it a promising candidate in all-comers patient population. For implanted medical devices, magnetic resonance (MR) imaging properties, including MR safety and compatibility, should be evaluated before its clinical use, especially for devices with intrinsic ferromagnetism. In this study, MR safety and compatibility of the IBS scaffold were evaluated based on a series of well-designed in-vitro, ex-vivo and in-vivo experiments, considering possible risks, including scaffold movement, over-heating, image artifact, and possible vessel injury, under typical MR condition. Traditional ASTM standards for MR safety and compatibility evaluation of intravascular devices were referred, but not only limited to that. The unique time-relevant MR properties of bioresorbable scaffolds were also discussed. Possible forces imposed on the scaffold during MR scanning and MR image artifacts gradually decreased along with scaffold degradation/absorption. Rigorous experiments designed based on a scientifically based rationale revealed that the IBS scaffold is MR conditional, though not MR compatible before complete absorption. The methodology used in the present study can give insight into the MR evaluation of magnetic scaffolds (bioresorbable) or stents (permanent).

3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering

A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of non-homogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.

Impact of the magnetic field on 3T3-E1 preosteoblasts inside SMART silk fibroin-based scaffolds decorated with magnetic nanoparticles.

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.

Mineralization of ytterbium-doped hydroxyapatite nanorod arrays in magnetic chitosan scaffolds improves osteogenic and angiogenic abilities for bone defect healing

Hydroxyapatite (HA) is a traditional bone repair material, but its poor osteogenic and angiogenic abilities hinder the clinical application for critical-sized bone defect healing. Herein, ytterbium-doped hydroxyapatite (YbHA) nanorod arrays in situ deposited in magnetic chitosan (CS) porous scaffolds, leading to create magnetic YbHA/CS (MYbHA/CS) nanohybrid scaffolds. We hypothesized that both magnetic SrFe12O19 nanoplates and Yb dopants in the functional scaffolds favored the osteogenesis and vascularization in bone defect regions. To prove the hypothesis, the osteogenic and angiogenic activities of MYbHA/CS scaffolds were investigated by using rat bone marrow mesenchymal stem cells (rBMSCs) and rat cranial defects as models. Fortunately, both the magnetic fields and Yb3+ ions as-derived from MYbHA/CS scaffolds remarkably up-regulated the expression of osteogenic-related genes by activating BMP-2/Smad pathway, and simultaneously increased the expression of vascular endothelial growth factor. In vivo rat cranial defect models further revealed that the combination effects between magnetic SrFe12O19 nanoplates and Yb dopants remarkably stimulated the in-growth of blood vessels and new bones into three-dimensional channels in the nanohybrid scaffolds. Hence, the modification of SrFe12O19 nanoplates and Yb dopants in bone scaffolds is a novel and promising strategy to accelerate bone defect healing.

Effect of Pulsed Electromagnetic Fields on Human Mesenchymal Stem Cells Using 3D Magnetic Scaffolds.

Alternative bone regeneration strategies that do not rely on harvested tissue or exogenous growth factors are needed. One of the major challenges in tissue reconstruction is recreating the bone tissue microenvironment using the appropriate combination of cells, scaffold, and stimulation to direct differentiation. This study presents a bone regeneration formulation that involves the use of human adipose‐derived mesenchymal stem cells (hASCs) and a three‐dimensional (3D) hydrogel scaffold based on self‐assembled RADA16 peptides containing superparamagnetic iron oxide nanoparticles (NPs). Although superparamagnetic NPs could be used as stimulus to manipulate the cell proliferation and differentiation, in this paper their use is explored for assisting osteogenic differentiation of hASCs in conjunction with direct stimulation by extremely low‐frequency pulsed electromagnetic fields (pEMFs). Cellular morphology, proliferation, and viability, as well as alkaline phosphatase activity, calcium deposition, and osteogenic capacity were monitored for cells cultured up to 21 days in the 3D construct. The results show that the pEMFs and NPs do not have any negative effect on cell viability, but instead distinctly induced early differentiation of hASCs to an osteoblastic phenotype, when compared with cells without biophysical stimulation. This effect is attributed to synergy between the pEMFs and NPs, which may have stimulated mechanotransduction pathways, which, in turn activated biochemical signals between cells to differentiate or proliferate. This approach may offer a safe and effective option for the treatment of non‐union bone fractures. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.

Magnetic scaffolds in oil spill applications

Reviewing the past developments and future possibilities of magnetic scaffolds in oil separation from oil spills.

The essential role of osteoclast-derived exosomes in magnetic nanoparticle-infiltrated hydroxyapatite scaffold modulated osteoblast proliferation in an osteoporosis model.

Magnetic hydroxyapatite (MHA) scaffolds promoted osteoblast proliferation in a model of osteoporosis through altering the osteoclast-derived exosomal cargo and decreasing the efficiency of exosome uptake by osteoblasts. Noticeably, certain proteins including ubiquitin, ATP and reactive oxygen species decreased in the osteoclast-derived exosomal cargo with MHA stimulation, while Rho kinase increased.

Dynamic viscoelasticity and magnetorheological property of magnetic hydrogels

Enable hydrogels with real-time controllable viscoelastic properties is of great significance for their clinical application. In this study, magnetic hydrogels were synthesized through a blending method. Scanning electron microscopy (SEM) was used to analyze the morphology of the magnetic hydrogels. The structure of magnetic hydrogels was analyzed by X-ray diffraction (XRD), Fourier transform infrared spectrometry (FT-IR) and swelling tests. Compared with the passive hydrogel scaffolds, the magnetic hydrogel scaffolds have similar porous morphology but a more flexible structure. Magnetic hydrogels show dynamic viscoelasticity and magnetic-induced shear storage modulus with increasing field strength. The reason is the Fe3O4 nanoparticles interact with each other under external magnetic field, thus change the microstructure of the magnetic hydrogels.

A magnetic micro-environment in scaffolds for stimulating bone regeneration

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.

A New Approach for the Fabrication of Cytocompatible PLLA-Magnetite Nanoparticle Composite Scaffolds.

Magnetic biomimetic scaffolds of poly(L-lactide) (PLLA) and nanoparticles of magnetite (nFe3O4) are prepared in a wide ratio of compositions by lyophilization for bone regeneration. The magnetic properties, cytotoxicity, and the in vitro degradation of these porous materials are closely studied. The addition of magnetite at 50 °C was found to produce an interaction reaction between the ester groups of the PLLA and the metallic cations of the magnetite, causing the formation of complexes. This fact was confirmed by the analysis of the infrared spectroscopy and the gel permeation chromatography test results. They, respectively, showed a displacement of the absorption bands of the carbonyl group (C=O) of the PLLA and a scission of the polymer chains. The iron from the magnetite acted as a catalyser of the macromolecular scission reaction, which determines the final biomedical applications of the scaffolds—it does so because the reaction shortens the degradation process without appearing to influence its toxicity. None of the samples studied in the tests presented cytotoxicity, even at 70% magnetite concentrations.

A novel magnetic bifunctional nanocomposite scaffold for photothermal therapy and tissue engineering

In recent years, porous bifunctional scaffolds with hyperthermal and tissue regeneration functions play an essential role in the efficient cancerous bone tumors treatment. In this work, the nanocomposite scaffolds of gelatin (polymer phase) and akermanite (ceramic phase) were prepared by entrapping carboxyl-functionalized multi-walled carbon nanotube (MWNT) and embedding magnetic nanoparticles of iron oxide into the porous matrix as photothermal conversion agents. The obtained scaffolds and their components were characterized using FTIR, FESEM, TEM, EDS, DLS, and VSM analysis. The mechanical properties of the prepared scaffolds were also investigated. The swelling behavior of the scaffolds in PBS as well as biodegradation and protein adsorption capability were evaluated. The addition of nanoparticles into the gelatin/akermanite matrix efficiently increased the adsorption of bovine serum albumin on the surface of the composite scaffold and contrarily decreased its degradation rate in the presence of lysozyme. The prepared scaffolds exhibited a high photothermal performance using NIR laser with different power intensity and irradiation time. Finally, the biocompatibility of the scaffold was confirmed using G292 osteoblastic cells through MTT assays. It can therefore be concluded that synthesized scaffolds have a great potential in bone tissue engineering and probably treatment of tumor related bone defects.