Fabrication of permeable tubular constructs from chemically modified chitosan with enhanced antithrombogenic property.

The failure of artificial vascular grafts in small diameter vessel replacement is mainly due to the early formation of thrombosis. To prevent the occurrence of thrombosis, much effort has been focused on developing an anti-thrombogenic coating of synthetic vascular prostheses or artificial conduits with improved anti-thrombogenic properties. Because surface coatings may be unstable for long-term applications, a bulk material with anti-thrombogenic property is desirable for the fabrication of vascular grafts or conduits. To this end, we have chemically modified chitosan by phthalization to derive an anti-thrombogenic material for the fabrication of vascular grafts. The chemical structure of phthalized chitosan was characterized with infrared spectroscopy. The hydrophilicity was examined with contact angle measurement, and the molecular weight distribution was measured using gel permeation chromatography (GPC). Protein adsorption, hemolysis, and platelet adhesion assays were used to confirm the enhanced anti-thrombogenic properties of this phthalized chitosan. Cytotoxicity and proliferation assays were performed to test its high biocompatibility. With its improved solubility and processibility, this phthalized chitosan was fabricated into selective permeable tubular constructs of varying sizes and morphology through a wet phase-inversion process. With improved anti-thrombogenic property, biocompatibility, and great processibility, phthalized chitosan has great potential as the material for the fabrication of small diameter vascular grafts.

[1]  Chia-Wen Lin,et al.  Surface characterization and platelet compatibility evaluation of surface-sulfonated chitosan membrane , 2001, Journal of biomaterials science. Polymer edition.

[2]  T. Matsuura,et al.  MEMBRANE CHARACTERIZATION BY SOLUTE TRANSPORT AND ATOMIC FORCE MICROSCOPY , 1998 .

[3]  N Nakabayashi,et al.  Preparation of non-thrombogenic materials using 2-methacryloyloxyethyl phosphorylcholine. , 2003, Biomaterials.

[4]  W. J. Wang,et al.  Covalent immobilization of chitosan and heparin on PLGA surface. , 2003, International journal of biological macromolecules.

[5]  J. Watanabe,et al.  Cellulose acetate hollow fiber membranes blended with phospholipid polymer and their performance for hemopurification , 2004, Journal of biomaterials science. Polymer edition.

[6]  Jiang Yuan,et al.  Platelet adhesive resistance of segmented polyurethane film surface-grafted with vinyl benzyl sulfo monomer of ammonium zwitterions. , 2003, Biomaterials.

[7]  J. Dutta,et al.  CHITIN AND CHITOSAN FOR VERSATILE APPLICATIONS , 2002 .

[8]  S. Kim,et al.  Effect of synthesis temperature of PEO-grafted PU/PS IPNs on surface morphology and in vitro blood compatibility , 2003, Journal of biomaterials science. Polymer edition.

[9]  N Nakabayashi,et al.  Why do phospholipid polymers reduce protein adsorption? , 1998, Journal of biomedical materials research.

[10]  S. W. Kim,et al.  Design of nonthrombogenic polymer surfaces for blood-contacting medical devices. , 1996, Blood purification.

[11]  Joseph D. Andrade,et al.  Blood compatibility of polyethylene oxide surfaces , 1995 .

[12]  P. Tresco,et al.  A simple instrument to characterize convective and diffusive transport of single hollow fibers of short length , 2001 .

[13]  D. H. Kim,et al.  Comparison of macropore, semipermeable, and nonpermeable collagen conduits in nerve repair. , 1993, Journal of reconstructive microsurgery.

[14]  Koon Gee Neoh,et al.  Physicochemical and blood compatibility characterization of polypyrrole surface functionalized with heparin , 2003, Biotechnology and bioengineering.

[15]  Richard E. Coggeshall,et al.  Nerve regeneration through holey silicone tubes , 1985, Brain Research.

[16]  Hitoshi Sashiwa,et al.  Chemically modified chitin and chitosan as biomaterials , 2004 .

[17]  R. Coggeshall,et al.  Permeable tubes increase the length of the gap that regenerating axons can span , 1987, Brain Research.

[18]  J. Zhang,et al.  Platelet adhesion onto segmented polyurethane surfaces modified by carboxybetaine , 2003, Journal of biomaterials science. Polymer edition.

[19]  M. Packham.  The Behavior of Platelets at Foreign Surfaces , 1988, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[20]  Jiang Yuan,et al.  Chemical graft polymerization of sulfobetaine monomer on polyurethane surface for reduction in platelet adhesion. , 2004, Colloids and surfaces. B, Biointerfaces.

[21]  K. Yao,et al.  Anticoagulation activity of crosslinked N‐sulfofurfuryl chitosan membranes , 2004 .

[22]  J. Zhang,et al.  Grafting sulfobetaine monomer onto the segmented poly(ether-urethane) surface to improve hemocompatibility , 2002, Journal of biomaterials science. Polymer edition.

[23]  Y. Iwasaki,et al.  Copolymers of 2-methacryloyloxyethyl phosphorylcholine (MPC) as biomaterials. , 2004, Bio-medical materials and engineering.

[24]  G. Lundborg,et al.  Neuronotrophic activities accumulate in vivo within silicone nerve regeneration chambers , 1983, Brain Research.

[25]  B. Nilsson,et al.  Optimal heparin surface concentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro. , 2003, Journal of biomedical materials research. Part A.

[26]  Linxu Si.  Synthesis Studies on Blood Compatible Materials(VII)──A Novel Kind of Platelet Adhesion Resistant Polymers , 2002 .

[27]  Y. Tamada,et al.  Anticoagulant effects of sulphonated polyisoprenes. , 1998, Biomaterials.

[28]  C. Sharma,et al.  Supported cell mimetic monolayers and their interaction with blood. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[29]  Anthony E. Pusateri,et al.  The Chitosan-Based Hemostatic Dressing: Experience in Current Combat Operations. , 2005, The Journal of trauma.

[30]  A. Domb,et al.  Chitosan chemistry and pharmaceutical perspectives. , 2004, Chemical reviews.

[31]  Tze-Wen Chung,et al.  Enhancement of the growth of human endothelial cells by surface roughness at nanometer scale. , 2003, Biomaterials.

[32]  Xuejun Wen,et al.  Fabrication and characterization of permeable degradable poly(DL-lactide-co-glycolide) (PLGA) hollow fiber phase inversion membranes for use as nerve tract guidance channels. , 2006, Biomaterials.

[33]  Makarand V Risbud,et al.  Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. , 2005, Biomaterials.

[34]  S. Kim,et al.  PEO-grafting on PU/PS IPNs for enhanced blood compatibility--effect of pendant length and grafting density. , 2002, Biomaterials.

[35]  R. Guidoin,et al.  Textile arterial prostheses: is water permeability equivalent to porosity? , 1987, Journal of biomedical materials research.

[36]  Seung‐Woo Cho,et al.  Small-Diameter Blood Vessels Engineered With Bone Marrow–Derived Cells , 2005, Annals of surgery.

[37]  J. Zhang,et al.  Reduced Platelet Adhesion on the Surface of Polyurethane Bearing Structure of Sulfobetaine , 2003, Journal of biomaterials applications.

[38]  D. Burgess,et al.  Transformation and motility of human platelets: details of the shape change and release reaction observed by optical and electron microscopy , 1979, The Journal of cell biology.

[39]  E. Doherty,et al.  Transport characterization of membranes for immunoisolation. , 1996, Biomaterials.

[40]  K. Ishihara,et al.  Preparation of blood-compatible hollow fibers from a polymer alloy composed of polysulfone and 2-methacryloyloxyethyl phosphorylcholine polymer. , 2002, Journal of biomedical materials research.

[41]  Yumin Du,et al.  Influence of functional groups on the in vitro anticoagulant activity of chitosan sulfate. , 2003, Carbohydrate research.

[42]  C. Cao,et al.  A novel solvent system for blending of polyurethane and heparin. , 2003, Biomaterials.

[43]  K. Ishihara,et al.  In vitro and ex vivo blood compatibility study of 2-methacryloyloxyethyl phosphorylcholine (MPC) copolymer-coated hemodialysis hollow fibers , 2003, Journal of Artificial Organs.

[44]  Jiang Yuan,et al.  Platelet adhesion and protein adsorption on silicone rubber surface by ozone-induced grafted polymerization with carboxybetaine monomer. , 2005, Colloids and surfaces. B, Biointerfaces.

[45]  M. Amiji.  Platelet adhesion and activation on an amphoteric chitosan derivative bearing sulfonate groups , 1998 .

[46]  S. Goodman,et al.  Platelet shape change and cytoskeletal reorganization on polyurethaneureas. , 1989, Journal of biomedical materials research.

[47]  S. Nishimura,et al.  Chemospecific manipulations of a rigid polysaccharide: syntheses of novel chitosan derivatives with excellent solubility in common organic solvents by regioselective chemical modifications , 1991 .

[48]  J M Courtney,et al.  Biomaterials for blood-contacting applications. , 1994, Biomaterials.

[49]  W. Park,et al.  Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. , 1995, Biomaterials.

[50]  W. Zhuang,et al.  Polyurethane vascular catheter surface grafted with zwitterionic sulfobetaine monomer activated by ozone. , 2004, Colloids and surfaces. B, Biointerfaces.