Integrated biomimetic carbon nanotube composites for in vivo systems.

As interest in using carbon nanotubes for developing biologically compatible systems continues to grow, biological inspiration is stimulating new directions for in vivo approaches. The ability to integrate nanotechnology-based systems in the body will provide greater successes if the implanted material is made to mimic elements of the biological milieu especially through tuning physical and chemical characteristics. Here, we demonstrate the highly successful capacity for in vivo implantation of a new carbon nanotube-based composite that is, itself, integrated with a hydroxyapatite-polymethyl methacrylate to create a nanocomposite. The success of this approach is grounded in finely tailoring the physical and chemical properties of this composite for the critical demands of biological integration. This is accomplished through controlling the surface modification scheme, which affects the interactions between carbon nanotubes and the hydroxyapatite-polymethyl methacrylate. Furthermore, we carefully examine cellular response with respect to adhesion and proliferation to examine in vitro compatibility capacity. Our results indicate that this new composite accelerates cell maturation through providing a mechanically competent bone matrix; this likely facilitates osteointegration in vivo. We believe that these results will have applications in a diversity of areas including carbon nanotube, regeneration, chemistry, and engineering research.

[1]  C. V. van Blitterswijk,et al.  Evaluation of hydroxylapatite/poly(L-lactide) composites: mechanical behavior. , 1992, Journal of biomedical materials research.

[2]  B. Bhushan Nanotribology and nanomechanics in nano/biotechnology , 2008, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[3]  A Tampieri,et al.  HA/alginate hybrid composites prepared through bio-inspired nucleation. , 2005, Acta biomaterialia.

[4]  D. Docheva,et al.  Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy , 2007, Journal of cellular and molecular medicine.

[5]  Hui Hu,et al.  Bone cell proliferation on carbon nanotubes. , 2006, Nano letters.

[6]  J. Whitfield,et al.  Novel carbon fiber composite for hip replacement with improved in vitro and in vivo osseointegration. , 2009, Journal of biomedical materials research. Part A.

[7]  Karen Lozano,et al.  Reinforcing Epoxy Polymer Composites Through Covalent Integration of Functionalized Nanotubes , 2004 .

[8]  Jonathan N. Coleman,et al.  Mechanical Reinforcement of Polymers Using Carbon Nanotubes , 2006 .

[9]  Luciano Merlini,et al.  Cationic PMMA nanoparticles bind and deliver antisense oligoribonucleotides allowing restoration of dystrophin expression in the mdx mouse. , 2009, Molecular therapy : the journal of the American Society of Gene Therapy.

[10]  Dimitris C. Lagoudas,et al.  Mechanical properties of surface-functionalized SWCNT/epoxy composites , 2008 .

[11]  U. Müller,et al.  Elastic properties of adhesive polymers. II. Polymer films and bond lines by means of nanoindentation , 2006 .

[12]  C. Viegas,et al.  Assessment of markers of bone formation under controlled environmental factors and their correlation with serum minerals in adult sheep as a model for orthopaedic research , 2008, Laboratory animals.

[13]  Sanjiv S Gambhir,et al.  A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. , 2008, Nature nanotechnology.

[14]  M. Yavropoulou,et al.  Osteoclastogenesis--current knowledge and future perspectives. , 2008, Journal of musculoskeletal & neuronal interactions.

[15]  R. Ritchie,et al.  Adhesion between biodegradable polymers and hydroxyapatite: Relevance to synthetic bone-like materials and tissue engineering scaffolds. , 2008, Acta biomaterialia.

[16]  J. FRASER STODDART,et al.  Noncovalent functionalization of single-walled carbon nanotubes. , 2009, Accounts of chemical research.

[17]  Lisa A. Pruitt,et al.  Nanoindentation of biological materials , 2006 .

[18]  A. Scaloni,et al.  A proteomic study on human osteoblastic cells proliferation and differentiation , 2006, Proteomics.

[19]  M. S. Burstone,et al.  HISTOCHEMICAL OBSERVATIONS ON ENZYMATIC PROCESSES IN BONES AND TEETH , 1960, Annals of the New York Academy of Sciences.

[20]  Molly M. Stevens,et al.  Biomaterials for bone tissue engineering , 2008 .

[21]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[22]  A. Billiau,et al.  Human Interferon: Mass Production in a Newly Established Cell Line, MG-63 , 1977, Antimicrobial Agents and Chemotherapy.

[23]  Peter X. Ma,et al.  Scaffolds for tissue fabrication , 2004 .

[24]  D. Robinson,et al.  Using Lessons from Cellular and Molecular Structures for Future Materials , 2007 .

[25]  L. Ambrosio,et al.  The soybean isoflavone genistein induces differentiation of MG63 human osteosarcoma osteoblasts. , 2006, The Journal of nutrition.

[26]  James M. Tour,et al.  Materials Science: Nanotube composites , 2007, Nature.

[27]  M. Karsdal,et al.  Local communication on and within bone controls bone remodeling. , 2009, Bone.

[28]  J. Bancroft,et al.  Theory and Practice of Histological Techniques , 1990 .

[29]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[30]  S. Ahzi,et al.  Hydroxyapatite Modified with Carbon‐Nanotube‐Reinforced Poly(methyl methacrylate): A Nanocomposite Material for Biomedical Applications , 2008 .

[31]  L. Falk,et al.  Pressureless sintered Al2O3–SiC nanocomposites , 2008 .

[32]  S. Lee,et al.  Static Magnetic Fields Up-regulate Osteoblast Maturity by Affecting Local Differentiation Factors , 2006, Clinical orthopaedics and related research.

[33]  A. Ahluwalia,et al.  Rapid-prototyped and salt-leached PLGA scaffolds condition cell morpho-functional behavior. , 2008, Journal of biomedical materials research. Part A.

[34]  Su A. Park,et al.  The characteristics of a hydroxyapatite-chitosan-PMMA bone cement. , 2004, Biomaterials.

[35]  Mark J. Pearcy,et al.  Implant retrieval studies of the wear and loosening of prosthetic joints: a review , 2000 .

[36]  D. Gerlier,et al.  Use of MTT colorimetric assay to measure cell activation. , 1986, Journal of immunological methods.

[37]  G. Pharr,et al.  An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments , 1992 .

[38]  J. Charnley,et al.  Total hip replacement by low-friction arthroplasty. , 1970, Clinical orthopaedics and related research.

[39]  R. Misra,et al.  Superior in vitro biological response and mechanical properties of an implantable nanostructured biomaterial: Nanohydroxyapatite-silicone rubber composite. , 2009, Acta biomaterialia.

[40]  Philip P. LeDuc,et al.  Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior , 2006, Annals of Biomedical Engineering.

[41]  V. Colvin The potential environmental impact of engineered nanomaterials , 2003, Nature Biotechnology.

[42]  William A. Curtin,et al.  CNT-reinforced ceramics and metals , 2004 .

[43]  L. Bonewald,et al.  Localization of 1,25-(OH)2D3-responsive alkaline phosphatase in osteoblast-like cells (ROS 17/2.8, MG 63, and MC 3T3) and growth cartilage cells in culture. , 1989, The Journal of biological chemistry.

[44]  J. San Román,et al.  Influence of cross-linked PMMA beads on the mechanical behavior of self-curing acrylic cements. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[45]  J. Gidley,et al.  Epidermal growth factor and calcitriol synergistically induce osteoblast maturation , 2004, Molecular and Cellular Endocrinology.

[46]  B. Boyan,et al.  Ceramic and PMMA particles differentially affect osteoblast phenotype. , 2002, Biomaterials.