摘要
(1)本实验首次用原位沉析法制备了壳聚糖多孔支架。通过扫描电子显微镜技术观察该支架的形貌,发现该支架具有三维有序微孔结构。酒精替代法测得支架的孔隙率高达88%,其抗压强度高达1.80MPa,有望作为骨组织工程支架应用于骨组织修复等领域。
(2)通过原位沉析法制备出壳聚糖/羟基磷灰石复合支架。本方法将羟基磷灰石前驱液与壳聚糖溶液混合均匀后进行原位沉析,羟基磷灰石原位生成于壳聚糖分子附近。经过红外吸收光谱法和X射线衍射法(XRD)证明本方法成功的将羟基磷灰石原位复合于壳聚糖支架中,SEM照片亦显示长约1.5μm宽约0.5μm的针状羟基磷灰石结晶均匀的分散在壳聚糖基体中。相关测试表明壳聚糖/羟基磷灰石复合支架孔隙率可达91.2%,抗压强度可达0.267MPa。
(3)通过原位沉析法制备了壳聚糖/四氧化三铁复合支架,并使用仿生矿化和仿生矿化-陈化法对其进行了改性。红外吸收光谱和XRD结果表明了四氧化三铁的生成以及该磁性粒子与壳聚糖具有良好的化学键结合。支架数码照片显示,复合有四氧化三铁的支架相较于纯壳聚糖支架表现出更加明显的层状叠加结构,而通过SEM观察发现,长约2μm宽0.5μm的柱状磁性粒子均匀的复合在壳聚糖基体中,通过仿生矿化和陈化手段可以调整其分布情况。所得支架抗压强度最高可达0.668MPa,孔隙率最高可达95%。
(1) Chitosan scaffolds were prepared by in-situ precipitation. Scanning electron microscope (SEM) were used to study features of the scaffolds and the results reveal that the scaffolds are three-dimensional oriented. The porosity was above 88% and compressive strength was as high as 1.80MPa.
(2) Chitosan (CS) /hydroxyapatite (HA) composite scaffolds were prepared by in-situ precipitation. HA was synthesised around the chitosan molecularchain. IR and XRD proved the exitance of HA. SEM photos showed that the needle-like HA particles evenly spreaded in the chitosan bulk. The porosity was around 91.2% and compressive strength was as high as 0.267MPa..
(3) Chitosan/Ferriferrous oxide (Fe_3O_4) composite scaffolds were prepared by in-situ precipitation and modified by mineralization and aging procedure. IR and XRD proved the exitance of Fe_3O_4 and the obvious effect of chemical bond between the magnetic particles and chitosan moleculars. The digital photographs showed that the scaffold with Fe_3O_4 has more obvious layered structure. SEM proved that column-shape magnetic particals spreaded in the chitosan bulks. The porosity was up to 95% and compressive strength was as high as 0.668MPa.
引文
[1]曹谊林,组织工程学,北京,科学出版社,2008,1-5。
[2]James D.Kretlow.Antonios G.Mikos.From Material to Tissue:Biomaterial Development,Scaffold Fabrication,and Tissue Engineering.MATERIALS INTERFACES AND ELECTROCHEMICAL PHENOMENA,2008,54.12:3048-3067.
[3]顾其胜,实用生物医用材料学,上海,上海科学技术出版社,2005,496-508。
[4]邓红文,骨生物学前沿,北京,高等教育出版社,2006,259-260。
[5]Peter SJ.Miller MJ,Yasko AW.Yaszemski MJ,Mikos AG.Polymer concepts in tissue engineering.J Biomed Mater Res.1998.43:422-427.
[6]Bucholz RW.Nonallograft osteoconductive bone graft substitutes.Clin Orthop Relat Res.2002.395:44-52.
[7]Molly,M.Stevens.Biomaterials for bone tissue engineering.Materials Today.2008.11(5):18-25.
[8]邓红文,骨生物学前沿,北京,高等教育出版社,2006,261-265.
[9]Pinar Yilgor,Kadriye Tuzlakoglu,Rui L.Reis,Nesrin Hasirci,Vasif Hasirci,Incorporation of a sequential BMP-2/BMP-7 delivery system into chitosan-based scaffolds for bone tissue engineering.Biomaterials,2009.30:3551-3559.
[10]Christiane Heinemann,Sascha Heinemann,Anja Lode,Anne Bernhardt,Hartmut Worch,Thomas Hanke.In Vitro Evaluation of Textile Chitosan Scaffolds for Tissue Engineering using Human Bone Marrow Stromal Cells.Biomacromolecules,2009,10:1305-1310.
[11]Mani T.Valarmathi,Michael J.Yost.Richard L.Goodwin,Jay D.Potts.The influence of proepicardial cells on the osteogenic potential of marrow stromal cells in a three-dimensional tubular scaffold.Biomaterials.2008,29:2203-2216.
[12]Lihua Li,Shan Ding,Changren Zhou.Preparation and Degradation of PLA/Chitosan Composite Materials.J Appl Polym Sci,2004,91:274-277.
[13] Michelle D. Kofron, Allison Griswold, Sangamesh G. Kumbar, Kylie Martin,Xuejun Wen, and Cato T. Laurencin. The Implications of Polymer Selection in Regenerative Medicine: A Comparison of Amorphous and Semi-Crystalline Polymer for Tissue Regeneration. Adv. Funct. Mater, 2009,19: 1351-1359.
[14] SuA Park, GeunHyung Kim, Yong Chul Jeon, YoungHo Koh, WanDoo Kim. 3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system. J Mater Sci: Mater Med, 2009, 20:229-234.
[15] Joshua R. Porter, Andrew Henson, Ketul C. Popat. Biodegradable poly(3-caprolactone) nanowires for bone tissue engineering applications. Biomaterials, 2009, 30: 780-788.
[16] Leda Klouda, Claudia M. Vaz, Anita Mol, Frank P. T. Baaijens, Carlijn V. C.Bouten. Effect of biomimetic conditions on mechanical and structural integrity of PGA/P4HB and electrospun PCL scaffolds. J Mater Sci: Mater Med, 2008, 19:1137-1144.
[17] M. Prabaharana, R. Jayakumar. Chitosan-graft-beta-cyclodextrin scaffolds with controlled drug release capability for tissue engineering applications. International Journal of Biological Macromolecules, 2009,44: 320-325.
[18] Michael J. Cooney, Carolin Lau, Mona Windmeisser, Bor Yann Liaw, Tamara Klotzbach and Shelley D. Minteer. Design of chitosan gel pore structure: towards enzyme catalyzed flow-through electrodes J. Mater. Chem., 2008, 18:667-674.
[19] Chien-Yang Hsieh, Sung-Pei Tsai, Ming-Hwa Ho, Da-Ming Wang, Chung-En Liu, Cheng-Hsuan Hsieh, Hsien-Chung Tseng, Hsyue-Jen Hsieh. Analysis of freeze-gelation and cross-linking processes for preparing porous chitosan scaffolds. Carbohydrate Polymers, 2007, 67: 124-132.
[20] Michael J. Cooney. Jana Petermann, Carolin Lau, Shelley D. Minteer.Characterization and evaluation of hydrophobically modified chitosan scaffolds:Towards design of enzyme immobilized flow-through electrodes. Carbohydrate Polymers, 2009. 75: 428-435.
[21] Shan-hui Hsu, Shu Wen Whu, Ching-Lin Tsai, Yuan-Hsuan Wu, Hui-Wan Chen, Kuo-Huang Hsieh. Chitosan as Scaffold Materials: Effects of Molecular Weight and Degree of Deacetylation. Journal of Polymer Research, 2004, 11: 141-147.
[22]Huanjun Zhou, Jiangchao Qian. Jing Wang. Wantong Yao. Changsheng Liu.Jianguo Chen, Xuehua Cao. Enhanced bioactivity of bone morphogenetic protein-2 with low dose of 2-N. 6-O-sulfated chitosan in vitro and in vivo.Biomaterials. 2009. 30: 1715-1724.
[23] Ana M. Martins, Marina I. Santos. Helena S. Azevedo, Patricia B. Malafaya.Rui L. Reis. Natural origin scaffolds with in situ pore forming capability for bone tissue engineering applications. Acta Biomaterialia. 2008, 4: 1637-1645.
[24] Dongwen Ren. Hongfu Yi. Wei Wang and Xiaojun Ma. The enzymatic degradation and swelling properties of chitosan matrices with different degrees of N-acetylation. Carbohydrate Research. 2005. 340: 2403-2410.
[25] Riccardo A.A. Muzzarelli. Chitins and chitosans for the repair of wounded skin.nerve, cartilage and bone. Carbohydrate Polymers. 2009. 76: 167-182.
[26] In-Yong Kim, Seog-Jin Seo, Hyun-Seuk Moon. Mi-Kyong Yoo. In-Young Park.Bom-Choi Kim. Chong-Su Cho. Chitosan and its derivatives for tissue engineering applications. Biotechnology Advances. 2008. 26: 1-21.
[27] Yanxia Zhu. Tianqing Liu, Kedong Song. Bo Jiang, Xuehu Ma. Zhanfeng Cui.Collagen-chitosan polymer as a scaffold for the proliferation of human adipose tissue-derived stem cells. J Mater Sci: Mater Med. 2009. 20: 799-808.
[28] Caren C. Leffler. Bernd W. Muller. Influence of the acid type on the physical and drug liberation properties of chitosan-gelatin sponges. International Journal of Pharmaceutics, 2000, 194: 229-237.
[29] Xiaohua Liu. Laura A. Smith. Jiang Hu. Peter X. Ma. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials.2009. 30: 2252-2258.
[30] Zhending She, Bofeng Zhang. Chenrui Jin, Qingling Feng, Yingxin Xu.Preparation and in vitro degradation of porous three-dimensional silk fibroin/chitosan scaffold. Polymer Degradation and Stability. 2008. 93:1316-1322.
[31] Nai-Yi Yuan, Yi-An Lin, Ming-Hwa Ho, Da-Ming Wang, Juin-Yih Lai,Hsyue-Jen Hsieh. Effects of the cooling mode on the structure and strength of porous scaffolds made of chitosan, alginate, and carboxymethyl cellulose by the freeze-gelation method. Carbohydrate Polymers, 2009, 78: 349-356.
[32] Yu Deng, Dengru Liu, Guocheng Du, Xiufen Li and Jian Chen. Preparation and characterization of hyaluronan/chitosan scaffold crosslinked by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. Polymer International, 2007,56: 738-745.
[33] Jennifer L. Moreau, Hockin H.K. Xu., Mesenchymal stem cell proliferation and differentiation on an injectable calcium phosphate-chitosan composite scaffold.Biomaterials, 2009, 30: 2675-2682.
[34] J Li, Z Y Qiu, L Zhou, T Lin, Y Wan, S Q Wang and S M Zhang. Novel calcium silicate/calcium phosphate composites for potential applications as injectable bone cements. Biomed. Mater, 2008, 3: 044102.
[35] Xing Zhang, Tsukasa Takahashi, Kenneth S. Vecchio. Development of bioresorbable Mg-substituted tricalcium phosphate scaffolds for bone tissue engineering. Materials Science and Engineering C. 2009, 29: 2003-2010.
[36] Hailuo Fu, Qiang Fu. Nai Zhou, Wenhai Huang, Mohamed N. Rahaman, Deping Wang, Xin Liu. In vitro evaluation of borate-based bioactive glass scaffolds prepared by a polymer foam replication method. Materials Science and Engineering C, 2009, 29: 2275-2281.
[37] ZHANG Xin, FU HaiLuo, LIU Xin, YAO AiHua, WANG DePing, HUANG WenHai, ZHAO Ying, JIANG XinQuan. In vitro bioactivity and cytocompatibility of porous scaffolds of bioactive borosilicate glasses. Chinese Sci Bull, 2009, 54: 3181—3186.
[38] Xin Liu, Wenhai Huang, Hailuo Fu, Aihua Yao, Deping Wang, Haobo Pan,William W. Lu, Xinquan Jiang, Xiuli Zhang. Bioactive borosilicate glass scaffolds: in vitro degradation and bioactivity behaviors. J Mater Sci: Mater Med,2009.20:1237-1243.
[39] Junjie Li. Yan Dou, Jun Yang, Yuji Yin, Hong Zhang, Fanglian Yao, Haibin Wang, Kangde Yao. Surface characterization and biocompatibility of micro- and nano-hydroxyapatite/chitosan-gelatin network films. Materials Science and Engineering C, 2009, 29: 1207-1215.
[40] Kim. B. S., Mooney D. J.. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 2001. 16: 224-230.
[41] Leong. K. F.. Cheah C. M. Chua C. K.. Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials, 2003. 24: 2363-2378.
[42] Anthony C. Jones. Christoph H. Arns. Dietmar W. Hutmacher, Bruce K.Milthorpe. Adrian P. Sheppard. Mark A. Knackstedt. The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth. Biomaterials, 2009. 30: 1440-1451.
[43] Zhihong Dong. Yubao Li. Qin Zou. Degradation and biocompatibility of porous nano-hydroxyapatite/polyurethane composite scaffold for bone tissue engineering. Applied Surface Science. 2009, 255: 6087-6091.
[44] Xianzhu Yu, Shu Cai. Guohua Xu. Wei Zhou, Dongmei Wang. Low temperature fabrication of high strength porous calcium phosphate and the evaluation of the osteoconductivity. J Mater Sci: Mater Med, 2009. 20: 2025-2034.
[45] Qiang Fu. Mohamed N. Rahaman. B. Sonny Bal. Roger F. Brown. In vitro cellular response to hydroxyapatite scaffolds with oriented pore architectures. Materials Science and Engineering C, 2009, 29: 2147-2153.
[46] Caren C. Leffler, Bernd W. Muller. Influence of the acid type on the physical and drug liberation properties of chitosan-gelatin sponges. International Journal of Pharmaceutics. 2000. 194: 229-237.
[47] Jiang Liuyun. Li Yubao. Xiong Chengdong. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering. Journal of Biomedical Science, 2009. 16: 65.
[48] Li Zhao. Jiang Chang, Wanyin Zhai. Preparation and HL-7702 cell functionality of titania/chitosan composite scaffolds. J Mater Sci: Mater Med. 2009. 20: 949-957.
[49] Liuyun Jiang. Yubao Li. Xuejiang Wang, Li Zhang, Jiqiu Wen, Mei Gong. Preparation and properties of nano-hydroxyapatite/chitosan/carboxymethyl cellulose composite scaffold. Carbohydrate Polymers, 2008, 74: 680-684.
[50] C B Machado, JMG Ventura, A F Lemos, J M F Ferreira, M F Leite and A M Goes. 3D chitosan-gelatin-chondroitin porous scaffold improves osteogenic differentiation of mesenchymal stem cells. Biomed. Mater., 2007, 2(2):124—131.
[51] Chien-Yang Hsieh, Sung-Pei Tsai, Ming-Hwa Ho, Da-Ming Wang, Chung-En Liu. Cheng-Hsuan Hsieh, Hsien-Chung Tseng, Hsyue-Jen Hsieh. Analysis of freeze-gelation and cross-linking processes for preparing porous chitosan scaffolds. Carbohydrate Polymers, 2007, 67: 124-132.
[52] Neeraj Kathuria, Anuj Tripathi, Kamal K Kar, Ashok Kumar. Synthesis and characterization of elastic and macroporous chitosan-gelatin cryogels for tissue engineering. Acta Biomaterialia, 2009, 5: 406^18.
[53] Arvind Sinha, Avijit Guha. Biomimetic patterning of polymer hydrogels with hydroxyapatite nanoparticles. Materials Science and Engineering C, 2009, 29:1330-1333.
[54] Patrcia B. Malafaya, Rui L. Reis. Bilayered chitosan-based scaffolds for osteochondral tissue engineering: Influence of hydroxyapatite on in vitro cytotoxicity and dynamic bioactivity studies in a specific double-chamber bioreactor. Acta Biomaterialia, 2009, 5: 644-660.
[55] P. B. MALAFAYA. A. J. PEDRO, A. PETERBAUER, C. GABRIEL, H. REDL,R. L. REIS. Chitosan particles agglomerated scaffolds for cartilage and osteochondral tissue engineering approaches with adipose tissue derived stem cells. JOURNAL OF MATERIALS SCIENCE: MATERIALS IN MEDICINE,2005, 16: 1077-1085.
[56] Christiane Heinemann, Sascha Heinemann, Anja Lode. Anne Bemhardt, Hartmut Worch, Thomas Hanke. In Vitro Evaluation of Textile Chitosan Scaffolds for Tissue Engineering using Human Bone Marrow Stromal Cells. Biomacromolecules, 2009, 10: 1305-1310.
[57]Syam P.Nukavarapu,Sangamesh G.Kumbar,Justin L.Brown,Nicholas R.Krogman,Arlin L.Weikel,Mark D.Hindenlang,Lakshmi S.Nair,Harry R.Allcock,Cato T.Laurencin.Polyphosphazene/Nano-Hydroxyapatite Composite Microsphere Scaffolds for Bone Tissue Engineering.Biomacromolecules,2008,9:1818-1825.
[58]Haohuai Liu.Li Zhang,Yi Zuo,Li Wang,Di Huang,Juan Shen,Pujiang Shi.Yubao Li.Preparation and Characterization of Aliphatic Polyurethane and Hydroxyapatite Composite Scaffold.Journal of Applied Polymer Science,2009,112:2968-2975.
[59]C.Cunha-Reis.K.TuzlaKoglu,E.Baas,Y.Yang,A.El Haj.R.L.Reis.Influence of porosity and fibre diameter on the degradation of chitosan fibre-mesh scaffolds and cell adhesion.J Mater Sci:Mater Med.2007.18:195-200.
[60]Xue-Hui Chu,Xiao-Lei Shi,Zhang-Qi Feng,Zhong-Ze Gu,Yi-Tao Ding.Chitosan nanofiber scaffold enhances hepatocyte adhesion and function.Biotechnol Lett,2009,31:347-352.
[61]Ana Rita C.Duarte,Joao F.Mano,Rui L.Reis.Preparation of chitosan scaffolds loaded with dexamethasone for tissue engineering applications using supercritical fluid technology.European Polymer Journal,2009,45:141-148.
[62]Peibiao Zhang.Zhongkui Hong,Ting Yu,Xuesi Chen,Xiabin Jing.In vivo mineralization and osteogenesis of nanocomposite scaffold of poly (lactide-co-glycolide) and hydroxyapatite surface-grafted with poly(L-lactide).Biomaterials.2009.30:58-70.
[63]Julia Will,Reinhold Melcher,Cornelia Treul,Nahum Travitzky.Ulrich Kneser.Elias Polykandriotis,Raymund Horch and Peter Greil.Porous ceramic bone scaffolds for vascularized bone tissue regeneration.J Mater Sci Mater Med.2008.19:2781-2790.
[64]顾其胜,实用生物医用材料学,上海,上海科学技术出版社,2005,193-196.
[65]Qingfeng Zan,Chen Wang,Limin Dong.Peng Cheng,Jiemo Tian.Effect of surface roughness of chitosan-based microspheres on cell adhesion.Applied Surface Science, 2008, 255: 401-403.
[66] Yanzhong Zhang, Jayarama Reddy Venugopal, Adel El-Turki, SeeramRamakrishna, Bo Su, Chwee Teck Lim. Electrospun biomimetic nanocomposite nanofibers of hydroxyapatite/chitosan for bone tissue engineering. Biomaterials,2008,29:4314-4322.
[67] Y. Zhai, F.Z. Cui, Y. Wang. Formation of nano-hydroxyapatite on recombinant human-like collagen fibrils. Current Applied Physics, 2005, 5: 429-432.
[68] Zhi-Hai Huang, Yin-Sheng Dong, Cheng-Lin Chu, Ping-Hua Lin.Electrochemistry assisted reacting deposition of hydroxyapatite in porouschitosan scaffolds. Materials Letters, 2008, 62: 3376-3378.
[69] Haifeng Liu, Hongbin Fan, Yuanlu Cui, Yiping Chen, Kangde Yao, and James C.H. Goh. Effects of the Controlled-Released Basic Fibroblast Growth Factor from Chitosan-Gelatin Microspheres on Human Fibroblasts Cultured on a Chitosan-Gelatin Scaffold. Biomacromolecules, 2007, 8: 1446-1455.
[70] Yan Huang, Stella Onyeri, Mbonda Siewe, Aliakbar Moshfeghian, Sundararajan V. Madihally. In vitro characterization of chitosan-gelatin scaffolds for tissue engineering. Biomaterials, 2005, 26: 7616-7627.
[71] Xiaoming Li, Qingling Feng, Fuzhai Cui. In vitro degradation of porous nano-hydroxyapatite/collagen/PLLA scaffold reinforced by chitin fibres. Materials Science and Engineering C, 2006, 26: 716 - 720.
[72] Hong Zhuang. Jun Ping Zheng, Hong Gao, Kang De Yao. In vitro biodegradation and biocompatibility of gelatin/montmorillonite-chitosan intercalated nanocomposite. J Mater Sci: Mater Med, 2007, 18: 951-957.
[73] Xufeng Niu, Qingling Feng, Mingbo Wang, Xiaodong Guo, Qixin Zheng. Porous nano-HA/collagen/PLLA scaffold containing chitosan microspheres for controlled delivery of synthetic peptide derived from BMP-2. Journal of Controlled Release, 2009, 134: 111-117.
[74] Zhang, L., Li, Y. B., Yang, A. P., Peng. X. L., Wang. X. J., & Zhang, X. Preparation and in vitro investigation of chitosan/nano-hydroxyapatite composite used as bone substitute materials. Journal of Materials Science: Materials in Medicine, 2005. 16:213-219.
[75] Zhang. L.. Li, Y. B.. Yang. A. P., Zuo. Y.. Lv. G. Y.. & Wei, J. The preparation and characterization of porous scaffold made of nano-hydroxyapatite/chitosan composite for bone tissue engineering. Functional Materials. 2005, 36: 314-317.
[76] Liuyun Jiang, Yubao Li, Xuejiang Wang. Li Zhang, Jiqiu Wen, Mei Gong.Preparation and properties of nano-hydroxyapatite/chitosan/carboxymethyl cellulose composite scaffold. Carbohydrate Polymers, 2008, 74: 680-684.
[77] Joao F. Mano. Graham Hungerford. Jose L. Gomez Ribelles. Bioactive poly(L-lactic acid)-chitosan hybrid scaffolds. Materials Science and Engineering C, 2008.28: 1356-1365.
[78] Hu. Q. L., Li. B. Q.. Wang. M.. & Shen. J. C. Preparation and characterization of biodegradable chitosan/hydroxyapatite nanocomposite rods via in situ hybridization: a potential material as internal fixation of bone fracture.Biomaterials. 2004. 25: 779-785.
[79] Hu. Q. L., Li. B. Q., Wang. M., & Shen. J. C. Preparation of Chitosan Hydroxyapatite Nanocomposite with Layered Structure via in-situ Compositing(in Chinese, with English abstract). CHEMICAL JOURNAL OF CHINESE UNIVERSITIES, 2004. 25: 1949-1952.
[80] Sundararajan V. Madihally. Howard W.T. Matthew. Porous chitosan scaffolds for tissue engineering. Biomaterials. 1999. 20:1133-1142.
[81] W.W. Thein-Han, R.D.K. Misra, Biomimetic chitosan-nanohydroxyapatite composite scaffolds for bone tissue engineering, Acta Biomaterialia, 2009. 5:1182-1197.
[82] Michael J. Cooney. Jana Petermann, Carolin Lau. Shelley D. Minteer. Characterization and evaluation of hydrophobically modified chitosan scaffolds:Towards design of enzyme immobilized flow-through electrodes. Carbohydrate Polymers, 2009. 75: 428-435.
[83] Alexandra Montembault. Christophe Viton. Alain Domard. Physico-chemical studies of the gelation of chitosan in a hydroalcoholic medium. Biomaterials.2005.26:933-943.
[84] Sebastien Ladet, Laurent Dacid, Alain Domard. Multi-membrane hydrogels.Nature, 2008. 452: 76-80.
[85] Jennifer Elisseeff. Structure starts to gel. Nature materials, 2008, 7: 271-273.
[86] Nadege Boucard, Christophe Viton, Diane Agay, Eliane Mari, Thierry Roger,Yves Chancerelle, Alain Domard. The use of physical hydrogels of chitosan for skin regeneration following third-degree burns. Biomaterials, 2007, 28:3478-3488.
[87] Suh J. K. & Matthew H. W.. Application of chitosan-based polysaccharide biomaterials in cartilage tissue engineering: A review. Biomaterials, 2000, 21:2589-2598.
[88] Khor E, Lim LY.. Implantable applications of chitin and chitosan. Biomaterials,2003, 24: 232339-49.
[89] Yamane S, Iwasaki N, Majima T, Funakoshi T, Masuko T, Harada K, Minami A,Monde K, Nishimura SI. Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering. Biomaterials 2005,26:611-619.
[90] Woo KM, Seo J, Zhang R, Ma PX. Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds. Biomaterials, 2007,28(16): 2622-30.
[91] Kong LJ, Gao Y, Cao WL, Gong YD, Zhao NM, Zhang XF. Preparation and characterization of nano-hydroxyapatite/chitosan composite scaffolds.JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 2005, 75: 275-282.
[92] Yamaguchi I, Tokuchi K, Fukuzaki H, Koyama Y. Takakuda K, Monma H,Tanaka T. Preparation and microstructure analysis of chitosan/hydroxyapatite nanocomposites. J Biomed Mater Res, 2001. 55: 20-7.
[93] Ma PX, Zhang RY, Xiao GZ, Franceschi R. Engineering new bone tissue in vitro on highly porous poly(a-hydroxyl acids)/hydroxyapatite composite scaffolds. J Biomed Mater Res, 2001, 54: 284-93.
[94] T.H. Ang, F.S.A. Sultana, D.W. Hutmacher, Y.S. Wong. J.Y.H. Fuh. X.M. Mo,H.T. Loh, E. Burdet, S.H. Teoh.. Fabrication of 3D chitosan-hydroxyapatite scaffolds using a robotic dispensing system. Materials Science and Engineering C. 2002. 20: 35-12.
[95] I. Manjubala. S. Scheler, Jorg Bossert. Klaus D. Jandt.. Mineralisation of chitosan scaffolds with nano-apatite formation by double diffusion technique.Acta Biomaterialia. 2006, 2: 75-84.
[96] Zhi-Hai Huang. Yin-Sheng Dong, Cheng-Lin Chu. Ping-Hua Lin.Electrochemistry assisted reacting deposition of hydroxyapatite in porous chitosan scaffolds. Materials Letters. 2008. 62: 3376-3378.
[97] Haiguang Zhao. Lie Ma. Changyou Gao. Jiacong Shen. Fabrication and properties of mineralized collagen-chitosan/hydroxyapatite scaffolds. Polym.Adv. Technol. 2008. 19: 1590-1596.
[98] Qiaoling Hu. Baoqiang Wang. Mang Wang, Jiacong Shen. Preparation and characterization of biodegradable chitosan/Hydroxyapatite nanocomposite rods via in situ hybridization: a potential material as internal fixation of bone fracture.Biomaterial, 2004. 25:779-785.
[99] Q. A. Pankhurst, J. Connolly. S. K. Jones. J. Dobson. Applications of magnetic nanoparticles in biomedicine. JOURNAL OF PHYSICS D-APPLIED PHYSICS.2003.36(13): 167-181.
[100] C. Bergemann. D. Muller-Schulte, J. Oster, L. A. Brassard. A. S. Lubbe.Magnetic ion-exchange nano- and microparticles for medical, biochemical and molecular biological applications. J. Magn. Mater, 1999. 194: 45-52.
[101] Y. R. Chemla. H. L. Crossman. Y. Poon. R. McDermott. R. Stevens. M. D.Alper, J. Clarke. Proc. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA . 2000, 97(26):14268-14272.
[102] J. Ugelstad. A. Berge. T. Ellingsen, R. Schmid, T.-N. Nilsen. P. C. Mork. P.Stenstad. E. Homes, O. Olsvik. PREPARATION AND APPLICATION OF NEW MONOSIZED POLYMER PARTICLES. PROGRESS IN POLYMER SCIENCE. 1992. 17(1): 87-161.
[103] Nitin S. Satarkar. J. Zach Hilt. Magnetic hydrogel nanocomposites for remote controlled pulsatile drug release. Journal of Controlled Release, 2008,130: 246-251.
[104] ShiXing Wang, Yang Zhou, Wen Guan, Bingjun Ding. Preparation and Characterization of Stimuli-Responsive Magnetic Nanoparticles. Nanoscale Res Lett. 2008, 3:289-294.
[105] P.A. Voltairas, D.I. Fotiadis, L.K. Michalis. Hydrodynamics of magnetic drug targeting. Journal of Biomechanics, 2002, 35: 813-821.
[106] D. R. Baselt, G. U. Lee, M. Natesan, S. W. Metzger, P. E. Sheehan, R. J. Colton.A biosensor based on magnetoresistance technology. BIOSENSORS & BIOELECTRONICS, 1998, 13: 731-739.
[107] F. C. MacKintosh, C. F. Schmidt. Microrheology. CURRENT OPINION IN COLLOID & INTERFACE SCIENCE, 1999,4(4): 300-307.
[108] M. C. Bautista, O. Bomati-Miguel, X. Zhao, M. P. Morales, T.Gonzalez-Carreno, R. P. deAlejo, J. Ruiz-Cabello, S. Veintemillas-Verdaguer. Comparative study of ferrofluids based on dextran-coated iron oxide and metal nanoparticles for contrast agents in magnetic resonance imaging.Nanotechnology, 2004, 15: 154-159.
[109] Min-yi Lou, Qiu-ling Jia, De-ping Wang, Bing Liu, Wen-hai Huang. The preparation and properties of monodisperse core-shell silica magnetic microspheres. J Mater Sci: Mater Med, 2008, 19: 217-223.
[110] Masanori Abe. Ferrite plating: a chemical method preparing oxide magnetic films at 24-100℃ and its applications. Electrochimica Acta, 2000, 45:3337-3343.
[111] Jong-Ryul Jeong. Seung-Jun Lee, Jong-Duk Kim, Sung-Chul Shin. Magnetic properties of g-Fe_2O_3 nanoparticles made by coprecipitation method. phys. stat.sol. (b), 2004, 241(7): 1593-1596.
[112] X.Q. Liu, M.D. Kaminski, J.S. Riffle, H.T. Chen. M. Torno, M.R. Finck, L.Taylor, A.J. Rosengart. Preparation and characterization of biodegradable magnetic carriers by single emulsion-solvent evaporation. JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS. 2007, 311(1): 84-87.
[113] N. Shpaisman, S. Margel. Synthesis and characterization of air-stable magnetic Fe composites microspheres of narrow size distribution. JOURNAL OF APPLIED POLYMER SCIENCE, 2008. 107(3): 1710-1717.
[114] Z.L. Liu. C.C. Liu. K.L. Yao. P.D. Liu. Q. Ning. Preparation and characterization of micron-sized magnetic microspheres by one-step suspension polymerization. JOURNAL OF APPLIED POLYMER SCIENCE. 2007, 105(3):1331-1335.
[115] A. Peppas. J. Hilt. A. Khademhosseini, R. Langer. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. ADVANCED MATERIALS, 2006, 18: 1345-1360.
[116] Santaneel Ghosh. Somesree GhoshMitra. Tong Cai, David R. Diercks Nathaniel C. Mills. DiAnna L. Hynds. Alternating Magnetic Field Controlled. Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility. Nanoscale Res Lett, 2010. 5:195-204.
[117] T.-J. Yoon, J. S. Kim. B. G. Kim. K. N. Yu. M.-H. Cho, J.-K. Lee.Multifunctional nanoparticles possessing a "magnetic motor effect" for drug or gene delivery. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2005.44(7): 1068-1071.
[118] P. Tartaj. C. J. Serna. Synthesis of monodisperse superparamagnetic Fe/silica nanospherical composites. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 2003. 125(51): 15754-15755.
[119] Sher Alam, Chokkalingam Anand, Radhakrishnan Logudurai. Veerappan V.Balasubramanian, Katsuhiko Ariga. Arumugam Chandra Bose. Toshiyuki Mori.Pavuluri Srinivasu. Ajayan Vinu. Comparative study on the magnetic properties of iron oxide nanoparticles loaded on mesoporous silica and carbon materials with different structure. Microporous and Mesoporous Materials. 2009. 121:178-184.
[120] Ai-Zheng Chen. Yun-Qing Kang. Xi-Ming Pu. Guang-Fu Yin. Yi Li. Jun-Yan Hu. Development of Fe3O4-poly(l-lactide) magnetic microparticles in supercritical CO_2. Journal of Colloid and Interface Science. 2009. 330: 317-322.
