In vitro study of a new biodegradable nanocomposite based on poly propylene fumarate as bone glue.

A novel poly propylene fumarate (PPF)-based glue which is reinforced by nanobioactive glass (NBG) particles and promoted by hydroxyethyl methacrylate (HEMA) as crosslinker agent, was developed and investigated for bone-to-bone bonding applications. In-vitro bioactivity, biodegradability, biocompatibility, and bone adhesion were tested and the results have verified that it can be used as bone glue. In an in-vitro condition, the prepared nanocomposite (PPF/HEMA/NBG) showed improved adhesion to wet bone surfaces. The combined tension and shear resistance between two wet bone surfaces was measured, and its maximum value was 9±59MPa. To investigate the bioactivity and biodegradability of the nanocomposite, it has been immersed in simulated body fluid (SBF). After 14days exposure to SBF, a hydroxyapatite (HA) layer formed on the surface of the composite confirms the bioactivity of this material. In the XRD pattern of the nanocomposite surface, the HA characteristic diffraction peak at θ=26 and 31.8 were observed. Also, by monitoring the weight change after 8weeks immersion in SBF, the mass loss was about 16.46wt%. It has been confirmed that this nanocomposite is a biodegradable material. Also, bioactivity and biodegradability of nanocomposite have been proved by SEM images. It has been showed that by using NBG particles and HEMA precursor, mechanical properties increased significantly. The ultimate tensile strength (UTS) of nanocomposite which contains 20% NBG and the ratio of 70/30wt% PPF/HEMA (PHB.732) was approximately 62MPa, while the UTS in the pure PPF/HEMA was about 32MPa. High cell viability in this nanocomposite (MTT assays, 85-95%) can be attributed to the NBG nature which contains calcium phosphate and is similar to physiological environment. Furthermore, it possesses biomineralization and biodegradation which significantly affected by impregnation of hydrophilic HEMA in the PPF-based polymeric matrix. The results indicated that the new synthesized biodegradable PPF/HEMA/NBG composite is suitable for biomedical applications especially as biodegradable bone glue in orthopedic surgeries.

[1]  Jianquan Wang,et al.  Swelling behaviors, tensile properties and thermodynamic studies of water sorption of 2-hydroxyethyl methacrylate/epoxy methacrylate copolymeric hydrogels , 2005 .

[2]  A. U. Daniels,et al.  Bioactive glass nanoparticles with negative zeta potential , 2011 .

[3]  D. Chappard,et al.  Polymerization of 2‐(hydroxyethyl)methacrylate by two different initiator/accelerator systems: a Raman spectroscopic monitoring , 2008 .

[4]  A. Schilling,et al.  Biologically and chemically optimized composites of carbonated apatite and polyglycolide as bone substitution materials. , 2001, Journal of biomedical materials research.

[5]  David Dean,et al.  Evaluation of the in vitro cytotoxicity of cross-linked biomaterials. , 2013, Biomacromolecules.

[6]  Dong-Woo Cho,et al.  Development of 3D PPF/DEF scaffolds using micro-stereolithography and surface modification , 2009, Journal of materials science. Materials in medicine.

[7]  D. Wise,et al.  PLGA bone plates reinforced with crosslinked PPF , 2002, Journal of materials science. Materials in medicine.

[8]  Joseph Kost,et al.  Handbook of Biodegradable Polymers , 1998 .

[9]  Jiang Chang,et al.  Preparation and characterization of nano-bioactive-glasses (NBG) by a quick alkali-mediated sol–gel method , 2007 .

[10]  David Farrar,et al.  Bone adhesives for trauma surgery: A review of challenges and developments , 2012 .

[11]  R. Dziak,et al.  Role of extracellular calcium influx in EGF-induced osteoblastic cell proliferation. , 1995, Bone.

[12]  D. Vashaee,et al.  Multilayer bioactive glass/zirconium titanate thin films in bone tissue engineering and regenerative dentistry , 2013, International journal of nanomedicine.

[13]  Stephanie Bryant,et al.  Degradable poly(2-hydroxyethyl methacrylate)-co-polycaprolactone hydrogels for tissue engineering scaffolds. , 2008, Biomacromolecules.

[14]  Antonios G Mikos,et al.  In vitro cytotoxicity of injectable and biodegradable poly(propylene fumarate)-based networks: unreacted macromers, cross-linked networks, and degradation products. , 2003, Biomacromolecules.

[15]  C. Ambrose,et al.  In vitro degradation of polymeric networks of poly(propylene fumarate) and the crosslinking macromer poly(propylene fumarate)-diacrylate. , 2003, Biomaterials.

[16]  A. Mikos,et al.  Synthesis of biodegradable poly(propylene fumarate) networks with poly(propylene fumarate)–diacrylate macromers as crosslinking agents and characterization of their degradation products , 2001 .

[17]  A. Boccaccini,et al.  Novel bioresorbable and bioactive composites based on bioactive glass and polylactide foams for bone tissue engineering , 2002, Journal of materials science. Materials in medicine.

[18]  T. Kokubo.  Surface chemistry of bioactive glass-ceramics , 1990 .

[19]  A. Mikos,et al.  Kinetics of poly(propylene fumarate) synthesis by step polymerization of diethyl fumarate and propylene glycol using zinc chloride as a catalyst , 2002, Journal of biomaterials science. Polymer edition.

[20]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[21]  F Burny,et al.  Tissues and bone adhesives--historical aspects. , 1998, Biomaterials.

[22]  Julian R Jones,et al.  Review of bioactive glass: from Hench to hybrids. , 2013, Acta biomaterialia.

[23]  Eric Loth,et al.  A Polyurethane-Based Nanocomposite Biocompatible Bone Adhesive , 2013 .

[24]  G. Michler,et al.  Nanocrystalline hydroxyapatite for bone repair: an animal study , 2010, Journal of materials science. Materials in medicine.

[25]  M. Fukase,et al.  Effect of elevated extracellular calcium on the proliferation of osteoblastic MC3T3-E1 cells:its direct and indirect effects via monocytes. , 1991, Biochemical and biophysical research communications.

[26]  T. Troczynski,et al.  In-situ preparation of poly(propylene fumarate)--hydroxyapatite composite. , 2005, Biomaterials.

[27]  H. Ohgushi,et al.  Osteogenic differentiation of cultured marrow stromal stem cells on the surface of bioactive glass ceramics. , 1996, Journal of biomedical materials research.

[28]  P Augat,et al.  In vivo investigations on composites made of resorbable ceramics and poly(lactide) used as bone graft substitutes. , 2001, Journal of biomedical materials research.

[29]  F. Monchau,et al.  In vitro studies of human and rat osteoclast activity on hydroxyapatite, beta-tricalcium phosphate, calcium carbonate. , 2002, Biomolecular engineering.

[30]  R Schnettler,et al.  Eigenschaften und Degradation eines neuartigen bioresorbierbaren Knochenklebers / Properties and Degradation of a New Bioresorbable Bone Glue , 2004, Biomedizinische Technik. Biomedical engineering.

[31]  Cato T Laurencin,et al.  Three-dimensional, bioactive, biodegradable, polymer-bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro. , 2003, Journal of biomedical materials research. Part A.

[32]  Eduardo Saiz,et al.  Bioactive glass coatings affect the behavior of osteoblast-like cells. , 2007, Acta biomaterialia.

[33]  W. Stark,et al.  Light-curable polymer/calcium phosphate nanocomposite glue for bone defect treatment. , 2010, Acta biomaterialia.

[34]  J. Mano,et al.  Development of bioactive and biodegradable chitosan-based injectable systems containing bioactive glass nanoparticles. , 2009, Acta biomaterialia.

[35]  W. Stark,et al.  Improved degradation and bioactivity of amorphous aerosol derived tricalcium phosphate nanoparticles in poly(lactide-co-glycolide) , 2006 .

[36]  João F. Mano,et al.  Polymer/bioactive glass nanocomposites for biomedical applications: A review , 2010 .

[37]  W. Hayes,et al.  Characterization of partially saturated poly(propylene fumarate) for orthopaedic application. , 1997, Journal of biomaterials science. Polymer edition.

[38]  Jayachandran Venkatesan,et al.  Nano-hydroxyapatite composite biomaterials for bone tissue engineering--a review. , 2014, Journal of biomedical nanotechnology.

[39]  A. Boccaccini,et al.  Electrophoretic deposition of gentamicin-loaded bioactive glass/chitosan composite coatings for orthopaedic implants. , 2014, ACS applied materials & interfaces.

[40]  M Epple,et al.  Effect of hydroxyapatite on the biodegradation and biomechanical stability of polyester nanocomposites for orthopaedic applications. , 2010, Acta biomaterialia.

[41]  A. Domb,et al.  Biodegradable bone cement compositions based on acrylate and epoxide terminated poly(propylene fumarate) oligomers and calcium salt compositions. , 1996, Biomaterials.

[42]  F. Moztarzadeh,et al.  Evaluation of effective parameters for the synthesis of poly(propylene fumarate) by response surface methodology , 2014 .

[43]  Shantikumar V. Nair,et al.  Novel Biodegradable Chitosan-gelatin/nano-bioactive Glass Ceramic Composite Scaffolds for Alveolar Bone Tissue Engineering , 2010 .

[44]  A. Boccaccini,et al.  Mechanical properties of biodegradable polymer sutures coated with bioactive glass , 2002, Journal of materials science. Materials in medicine.

[45]  R. Langer,et al.  The formation of propylene fumarate oligomers for use in bioerodible bone cement composites , 1990 .

[46]  Julian R Jones,et al.  Optimising bioactive glass scaffolds for bone tissue engineering. , 2006, Biomaterials.