3D-printed magnetic Fe3O4/MBG/PCL composite scaffolds with multifunctionality of bone regeneration, local anticancer drug delivery and hyperthermia.

In this study, three-dimensional (3D) magnetic Fe3O4 nanoparticles containing mesoporous bioactive glass/polycaprolactone (Fe3O4/MBG/PCL) composite scaffolds have been fabricated by the 3D-printing technique. The physiochemical properties, in vitro bioactivity, anticancer drug delivery, mechanical strength, magnetic heating ability and cell response of Fe3O4/MBG/PCL scaffolds were systematically investigated. The results showed that Fe3O4/MBG/PCL scaffolds had uniform macropores of 400 μm, high porosity of 60% and excellent compressive strength of 13-16 MPa. The incorporation of magnetic Fe3O4 nanoparticles into MBG/PCL scaffolds did not influence their apatite mineralization ability but endowed excellent magnetic heating ability and significantly stimulated proliferation, alkaline phosphatase (ALP) activity, osteogenesis-related gene expression (RUNX2, OCN, BSP, BMP-2 and Col-1) and extra-cellular matrix (ECM) mineralization of human bone marrow-derived mesenchymal stem cells (h-BMSCs). Moreover, using doxorubicin (DOX) as a model anticancer drug, Fe3O4/MBG/PCL scaffolds exhibited a sustained drug release for use in local drug delivery therapy. Therefore, the 3D-printed Fe3O4/MBG/PCL scaffolds showed the potential multifunctionality of enhanced osteogenic activity, local anticancer drug delivery and magnetic hyperthermia.

[1]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[2]  H. Chambers,et al.  Complications of iliac crest bone graft harvesting. , 1996, Clinical orthopaedics and related research.

[3]  M. Bostrom,et al.  Biosynthetic bone grafting. , 1999, Clinical orthopaedics and related research.

[4]  H. M. Kim,et al.  In vitro bone formation on a bone-like apatite layer prepared by a biomimetic process on a bioactive glass-ceramic. , 2000, Journal of biomedical materials research.

[5]  D. Maysinger,et al.  Polycaprolactone-b-poly(ethylene oxide) copolymer micelles as a delivery vehicle for dihydrotestosterone. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[6]  Stephen E. Feinberg,et al.  An image-based approach for designing and manufacturing craniofacial scaffolds. , 2000, International journal of oral and maxillofacial surgery.

[7]  I Zein,et al.  Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. , 2001, Journal of biomedical materials research.

[8]  Dietmar W. Hutmacher,et al.  Evaluation of Ultra-Thin Poly(ε-Caprolactone) Films for Tissue-Engineered Skin , 2001 .

[9]  A. ADoefaa,et al.  ? ? ? ? f ? ? ? ? ? , 2003 .

[10]  H. Honda,et al.  Hyperthermia using magnetite cationic liposomes for hamster osteosarcoma , 2004, Biomagnetic research and technology.

[11]  Hiroyuki Honda,et al.  Magnetite nanoparticle-loaded anti-HER2 immunoliposomes for combination of antibody therapy with hyperthermia. , 2004, Cancer letters.

[12]  Masahiro Saito,et al.  Alveolar Bone Marrow as a Cell Source for Regenerative Medicine: Differences Between Alveolar and Iliac Bone Marrow Stromal Cells , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  J. Dobson,et al.  Magnetic micro- and nanoparticle mediated activation of mechanosensitive ion channels. , 2005, Medical engineering & physics.

[14]  Z. Wu,et al.  Synthesis and characterization of functionalized silica-coated Fe3O4 superparamagnetic nanocrystals for biological applications , 2005 .

[15]  D. Zhao,et al.  The in-vitro bioactivity of mesoporous bioactive glasses. , 2006, Biomaterials.

[16]  Tadashi Kokubo,et al.  How useful is SBF in predicting in vivo bone bioactivity? , 2006, Biomaterials.

[17]  Dietmar Werner Hutmacher,et al.  State of the art and future directions of scaffold‐based bone engineering from a biomaterials perspective , 2007, Journal of tissue engineering and regenerative medicine.

[18]  L. Du,et al.  Effects of static magnetic fields on the voltage-gated potassium channel currents in trigeminal root ganglion neurons , 2007, Neuroscience Letters.

[19]  Alidad Amirfazli,et al.  Magnetic nanoparticles hit the target , 2007, Nature Nanotechnology.

[20]  A. Uchida,et al.  Novel hyperthermia for metastatic bone tumors with magnetic materials by generating an alternating electromagnetic field , 2007, Clinical & Experimental Metastasis.

[21]  Jean-Paul Fortin,et al.  Intracellular heating of living cells through Néel relaxation of magnetic nanoparticles , 2008, European Biophysics Journal.

[22]  Drug delivery: the heart of the matter. , 2008, Nature materials.

[23]  A. Jordan,et al.  Clinical applications of magnetic nanoparticles for hyperthermia , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[24]  R. Issels Hyperthermia adds to chemotherapy. , 2008, European journal of cancer.

[25]  S. Heo,et al.  Hierarchically mesoporous-macroporous bioactive glasses scaffolds for bone tissue regeneration. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[26]  W. Mutschler,et al.  Tissue engineering for bone defect healing: an update on a multi-component approach. , 2008, Injury.

[27]  Jianlin Shi,et al.  A mesoporous bioactive glass/polycaprolactone composite scaffold and its bioactivity behavior. , 2008, Journal of biomedical materials research. Part A.

[28]  P Stroeve,et al.  Cell toxicity of superparamagnetic iron oxide nanoparticles. , 2009, Journal of colloid and interface science.

[29]  Yin-Kai Chen,et al.  The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles. , 2009, Biomaterials.

[30]  Stefan Kaskel,et al.  Comparison of the in vitro bioactivity and drug release property of mesoporous bioactive glasses (MBGs) and bioactive glasses (BGs) scaffolds , 2009 .

[31]  Aldo R Boccaccini,et al.  Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds , 2010, Journal of The Royal Society Interface.

[32]  Ping Yang,et al.  Magnetic Fe3O4 nanoparticles and chemotherapy agents interact synergistically to induce apoptosis in lymphoma cells , 2010, International journal of nanomedicine.

[33]  D. Hutmacher,et al.  Ovine bone‐ and marrow‐derived progenitor cells and their potential for scaffold‐based bone tissue engineering applications in vitro and in vivo , 2010, Journal of tissue engineering and regenerative medicine.

[34]  J. Meng,et al.  Paramagnetic nanofibrous composite films enhance the osteogenic responses of pre-osteoblast cells. , 2010, Nanoscale.

[35]  G. Wang,et al.  A novel calcium phosphate ceramic–magnetic nanoparticle composite as a potential bone substitute , 2010, Biomedical materials.

[36]  M. Vallet‐Regí,et al.  Interaction of an ordered mesoporous bioactive glass with osteoblasts, fibroblasts and lymphocytes, demonstrating its biocompatibility as a potential bone graft material. , 2010, Acta biomaterialia.

[37]  A Tampieri,et al.  A novel route in bone tissue engineering: magnetic biomimetic scaffolds. , 2010, Acta biomaterialia.

[38]  Da-li Zhou,et al.  Synthesis and characterization of magnetic bioactive glass-ceramics containing Mg ferrite for hyperthermia , 2010 .

[39]  Yang Xu,et al.  Carbon-covered magnetic nanomaterials and their application for the thermolysis of cancer cells , 2010, International journal of nanomedicine.

[40]  J. Rose,et al.  Inorganic manufactured nanoparticles: how their physicochemical properties influence their biological effects in aqueous environments. , 2010, Nanomedicine.

[41]  Xiabin Jing,et al.  Fabrication and Drug Delivery of Ultrathin Mesoporous Bioactive Glass Hollow Fibers , 2010 .

[42]  Daniela Guarnieri,et al.  Surface investigation on biomimetic materials to control cell adhesion: the case of RGD conjugation on PCL. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[43]  C. Kumar,et al.  Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. , 2011, Advanced drug delivery reviews.

[44]  Yuanhua Lin,et al.  Magnetic biodegradable Fe3O4/CS/PVA nanofibrous membranes for bone regeneration , 2011, Biomedical materials.

[45]  Morteza Mahmoudi,et al.  Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. , 2011, Advances in colloid and interface science.

[46]  Martin R. Lohe,et al.  Heating and separation using nanomagnet-functionalized metal-organic frameworks. , 2011, Chemical communications.

[47]  S. Teoh,et al.  Discontinuous release of bone morphogenetic protein-2 loaded within interconnected pores of honeycomb-like polycaprolactone scaffold promotes bone healing in a large bone defect of rabbit ulna. , 2011, Tissue engineering. Part A.

[48]  P. Raab,et al.  Biphasic bone substitute and fibrin sealant for treatment of benign bone tumours and tumour-like lesions , 2011, International Orthopaedics.

[49]  María Vallet-Regí,et al.  Bioceramics: From Bone Regeneration to Cancer Nanomedicine , 2011, Advanced materials.

[50]  Gianaurelio Cuniberti,et al.  Three-dimensional printing of hierarchical and tough mesoporous bioactive glass scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability. , 2011, Acta biomaterialia.

[51]  Min Lai,et al.  Surface functionalization of TiO2 nanotubes with bone morphogenetic protein 2 and its synergistic effect on the differentiation of mesenchymal stem cells. , 2011, Biomacromolecules.

[52]  Yu Chen,et al.  An emulsification–solvent evaporation route to mesoporous bioactive glass microspheres for bisphosphonate drug delivery , 2012, Journal of Materials Science.

[53]  Francesco Baino,et al.  Three-dimensional glass-derived scaffolds for bone tissue engineering: current trends and forecasts for the future. , 2011, Journal of biomedical materials research. Part A.

[54]  P. Padmanabhan,et al.  Bimodal magnetic–fluorescent probes for bioimaging , 2011, Microscopy research and technique.

[55]  Eduardo Saiz,et al.  Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives. , 2011, Materials science & engineering. C, Materials for biological applications.

[56]  Earl Zastrow,et al.  Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer , 2011, Physics in medicine and biology.

[57]  Jiang Chang,et al.  Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application , 2012, Interface Focus.

[58]  Thikra Mustafa,et al.  Multifunctional Magnetic Nanoparticles for Synergistic Enhancement of Cancer Treatment by Combinatorial Radio Frequency Thermolysis and Drug Delivery , 2012, Advanced healthcare materials.

[59]  M. Vallet‐Regí,et al.  Revisiting bioceramics: Bone regenerative and local drug delivery systems , 2012 .

[60]  Pietro Favia,et al.  Improved osteoblast cell affinity on plasma-modified 3-D extruded PCL scaffolds. , 2013, Acta biomaterialia.

[61]  J. Meng,et al.  Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field enhance osteogenesis for bone repair in vivo , 2013, Scientific Reports.

[62]  Yongxiang Luo,et al.  Hierarchical mesoporous bioactive glass/alginate composite scaffolds fabricated by three-dimensional plotting for bone tissue engineering , 2012, Biofabrication.

[63]  Changqing Zhang,et al.  Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration. , 2014, Acta biomaterialia.