Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field enhance osteogenesis for bone repair in vivo

A novel nanofibrous composite scaffold composed of super-paramagnetic γ-Fe2O3 nanoparticles (MNP), hydroxyapatite nanoparticles (nHA) and poly lactide acid (PLA) was prepared using electrospinning technique. The scaffold well responds extern static magnetic field with typical saturation magnetization value of 0.049 emu/g as well as possesses nanofibrous architecture. The scaffolds were implanted in white rabbit model of lumbar transverse defects. Permanent magnets are fixed in the rabbit cages to provide static magnetic field for the rabbits post surgery. Results show that MNP incorporated in the nanofibers endows the scaffolds super-paramagnetic responsive under the applied static magnetic field, which accelerates new bone tissue formation and remodeling in the rabbit defect. The scaffold also exhibits good compatibility of CK, Cr, ALT and ALP within normal limits in the serum within 110 days post implantation. In conclusion, the super-paramagnetic responding scaffold with applying of external magnetic field provides a novel strategy for scaffold-guided bone repair.

[1]  J. Torbet,et al.  Oriented fibrin gels formed by polymerization in strong magnetic fields , 1981, Nature.

[2]  P. Vassilev,et al.  Parallel arrays of microtubules formed in electric and magnetic fields. , 1982, Bioscience reports.

[3]  P. Vassilev,et al.  Parallel arrays of microtubles formed in electric and magnetic fields , 1982 .

[4]  N. Murthy,et al.  Liquid crystallinity in collagen solutions and magnetic orientation of collagen fibrils , 1984, Biopolymers.

[5]  J. Torbet,et al.  Magnetic alignment of collagen during self-assembly. , 1984, The Biochemical journal.

[6]  W. Enneking,et al.  Electromagnetic stimulation of canine bone grafts. , 1984, The Journal of bone and joint surgery. American volume.

[7]  C. R. Howlett,et al.  Effect of a static magnetic field on fracture healing in a rabbit radius. Preliminary results. , 1987, Clinical orthopaedics and related research.

[8]  T. Takano-Yamamoto,et al.  Effect of a Pulsing Electromagnetic Field on Demineralized Bone-matrix-induced Bone Formation in a Bony Defect in the Premaxilla of Rats , 1992, Journal of dental research.

[9]  Muneyuki Date,et al.  Diamagnetic orientation of blood cells in high magnetic field , 1992 .

[10]  Muneyuki Date,et al.  Orientation of erythrocytes in a strong static magnetic field. , 1993 .

[11]  Shoogo Ueno,et al.  Effects of magnetic fields on fibrin polymerization and fibrinolysis , 1993 .

[12]  M. Date,et al.  Orientation of erythrocytes in a strong static magnetic field. , 1993, Blood.

[13]  N. Kawaguchi,et al.  Effects of a strong static magnetic field on blood platelets. , 1993, Platelets.

[14]  Shoogo Ueno,et al.  Effects of magnetic fields on fibrinolysis , 1994 .

[15]  Muneyuki Date,et al.  Effects of static magnetic fields of erythrocyte rheology , 1995 .

[16]  M. Heilmann,et al.  Use of Electromagnetic Fields in a Spinal Fusion: A Rabbit Model , 1997, Spine.

[17]  Y. Ikada,et al.  Effects of static magnetic field on bone formation of rat femurs. , 1998, Medical engineering & physics.

[18]  M. Brookes,et al.  The effects of pulsed electromagnetism on fresh fracture healing: osteochondral repair in the rat femoral groove. , 1998, Orthopedics.

[19]  U Bosch,et al.  The Proliferative Response of Isolated Human Tendon Fibroblasts to Cyclic Biaxial Mechanical Strain * , 2000, The American journal of sports medicine.

[20]  D Kaspar,et al.  Dynamic cell stretching increases human osteoblast proliferation and CICP synthesis but decreases osteocalcin synthesis and alkaline phosphatase activity. , 2000, Journal of biomechanics.

[21]  D. Burr,et al.  Recovery periods restore mechanosensitivity to dynamically loaded bone. , 2001, The Journal of experimental biology.

[22]  A. Grodzinsky,et al.  Tissue shear deformation stimulates proteoglycan and protein biosynthesis in bovine cartilage explants. , 2001, Archives of biochemistry and biophysics.

[23]  Shoogo Ueno,et al.  Strong Static Magnetic Field Stimulates Bone Formation to a Definite Orientation In Vitro and In Vivo , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  T. Kumagai,et al.  Physical stress by magnetic force accelerates differentiation of human osteoblasts. , 2003, Biochemical and biophysical research communications.

[25]  S M Perren,et al.  The influence of cyclic compression and distraction on the healing of experimental tibial fractures , 2004, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[26]  P. Giannoudis,et al.  Fracture healing: the diamond concept. , 2007, Injury.

[27]  Yu Zhang,et al.  Synthesis, characterization, and application of composite alginate microspheres with magnetic and fluorescent functionalities , 2009 .

[28]  J. Glowacki,et al.  Cell-free and cell-based approaches for bone regeneration , 2009, Nature Reviews Rheumatology.

[29]  M. Prabhakaran,et al.  Biomimetic hydroxyapatite-containing composite nanofibrous substrates for bone tissue engineering , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[30]  Antonio Gloria,et al.  Polymer-based composite scaffolds for tissue engineering. , 2010, Journal of applied biomaterials & biomechanics : JABB.

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

[32]  Nonmonotonic evolution of the blocking temperature in dispersions of superparamagnetic nanoparticles , 2010, 1011.2650.

[33]  Peter X Ma,et al.  Biomimetic nanofibrous scaffolds for bone tissue engineering. , 2011, Biomaterials.

[34]  L. Ghasemi‐Mobarakeh,et al.  Electrospun composite nanofibers for tissue regeneration. , 2011, Journal of nanoscience and nanotechnology.

[35]  Chengtie Wu,et al.  Mesoporous bioactive glasses as drug delivery and bone tissue regeneration platforms. , 2011, Therapeutic delivery.

[36]  Filippo Graziani,et al.  Stimulation of Bone Formation and Fracture Healing with Pulsed Electromagnetic Fields: Biologic Responses and Clinical Implications , 2011, International journal of immunopathology and pharmacology.

[37]  Antonio Gloria,et al.  A Basic Approach Toward the Development of Nanocomposite Magnetic Scaffolds for Advanced Bone Tissue Engineering , 2011 .

[38]  F. Jaberi,et al.  A moderate-intensity static magnetic field enhances repair of cartilage damage in rabbits. , 2011, Archives of medical research.

[39]  P. Giannoudis,et al.  Bone graft substitutes: What are the options? , 2012, The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland.

[40]  C. Hung,et al.  Magnetic Hydroxyapatite Bone Substitutes to Enhance Tissue Regeneration: Evaluation In Vitro Using Osteoblast-Like Cells and In Vivo in a Bone Defect , 2012, PloS one.

[41]  B. Chalidis,et al.  Pulsed electromagnetic fields for the treatment of tibial delayed unions and nonunions. A prospective clinical study and review of the literature , 2012, Journal of Orthopaedic Surgery and Research.

[42]  P. Ma,et al.  Nanofiber-based delivery of bioactive agents and stem cells to bone sites. , 2012, Advanced drug delivery reviews.

[43]  Utpal Bora,et al.  Silk Fibroin in Tissue Engineering , 2012, Advanced healthcare materials.

[44]  Younan Xia,et al.  Electrospun Nanofibers for Regenerative Medicine , 2012, Advanced healthcare materials.

[45]  Z. Gu,et al.  Magnetic responsive hydroxyapatite composite scaffolds construction for bone defect reparation , 2012, International journal of nanomedicine.

[46]  Chengtie Wu,et al.  Mesoporous bioactive glasses for drug delivery and bone tissue regeneration , 2013 .

[47]  Robert J. Kane,et al.  Biomimetic Nanofibrous Scaffolds for Bone Tissue Engineering Applications , 2013 .

[48]  A. Tampieri,et al.  Magnetic poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering , 2013, Journal of The Royal Society Interface.

[49]  R. Leesungbok,et al.  The Effects of a Static Magnetic Field on Bone Formation Around a Sandblasted, Large-Grit, Acid-Etched–Treated Titanium Implant , 2013 .