|
|
Effects of Matrigel on the Biocompatibility of Implantable Glucose Sensor Outer Materials Chitosan |
Shen Hao1, Liu Jun2, Jing Weiwei3, Suo Yongkuan1, Chang Shijie1, Sha Xianzheng1#* |
1.(Department of Biomedical Engineering, School of Fundamental Sciences, China Medical University, Shenyang 110122,China) 2.(The First Affiliated Hospital of Xiamen University,Xiamen 361000, Fujian, China); 3.(The First Hospital Affiliated of China Medical University, Shenyang 110001,China) |
|
|
Abstract Currently implantable glucose sensors cannot attain normally work. Chitosan has the characteristics of non-toxic, biodegradable and biocompatible, allowing a good candidate for uses as protective films of the outer layer of the sensors. However, it still cannot meet the requirements in clinical practice The aim of this study was to investigate the effects of Matrigel with different concentrations on the biocompatibility of porous chitosan membranes. We used a template leaching technique to prepare porous chitosan membranes (PCSMs). Silica gel was used as the porogen. PCSMs were coated with Matrigel, by dropping different concentrations of Matrigel (10, 15, 20 mg/mL). The PCSMs coated with or without Matrigel were implanted into the back subcutaneous tissues of male SD rats. The implanted membranes with surrounding tissues were taken out at 1, 2, 4, 6, 8, 10 weeks. Paraffin section was made with routine procedure. Inflammatory reaction, fibrous capsule thickness and vascular density around the membrane were analyzed by using morphological method and statistical method, comprehensively discussed the biological compatibility of membrane materials were evaluated comprehensively. Morphological observation: nuclei around the membranes were obvious at day 7 and day 14. The number of the inflammatory cells around the PCSMs with different concentrations of Matrigel was less than those of the PCSMs (control group) at the first 7 days. Then the inflammatory cells of the experimental group (with Matrigel) were higher than that of the porous chitosan membrane (control group) at day 14. Variance analysis showed no significant differences between the two groups. Fibrous capsule began to form at day 28, accompanying inflammatory cells decreased, and some collagen accumulated on the surface of membranes. The fibrous capsule became dense over time, the thickness of fibrous capsule decreased obviously at day 56 and day 70. The thickness of fibrous capsule thickness of the experimental group was less than the control group. Variance analysis results showed that the significant difference between experimental group and control group (P< 0.05). Using Bonferroni method, the difference between the control group and experimental group with the 20 mg/mL Matrigel was significantly different at day 42, day 56 and day 70. Near the skin, the P values were 0.01, 0.035 and 0.024; near muscle the p values were 0.036, 0.047 and 0.210. No obvious difference between the other groups (P>0.05). Vascular density around the membranes of each group increased overtime. The general difference between the experimental group and control group was not significant. However differences among the individual data were obvious. Vascular density of some of the PCSM coated with Matrigel was lower than that of the PCSM group. In general, Matrigel can improve the biocompatibility of the porous chitosan membranes to some degree. This can be reflected by the animal experiments.
|
Received: 05 March 2018
|
|
|
|
|
[1] Morais J, Papadimitrakopoulos F, Burgess D. Biomaterials/tissue interactions: Possible solutions to overcome foreign body response [J]. AAPS J, 2010 12(2): 188-196. [2] Onuki Y, Bhardwaj U, Papadimitrakopoulos F, et al. A review of the biocompatibility of implantable devices: Current challenges to overcome foreign body response [J]. J Diabetes Sci Technol, 2008, 2(6): 1003-1015. [3] Turner RF, Harrison DJ, Rajotte RV. Preliminary in vivo biocompatibility studies on perfluorosulphonic acid polymer membranes for biosensor applications [J]. Biomaterials, 1991, 12(4): 361-368. [4] Matsumoto T, Saito S, Ikeda S. A multilayer membrane amperometric glucose sensor fabricated using planar techniques for large-scale production [J]. Biotechnol, 2006, 122(2): 267-273. [5] Kvist PH, Iburg T, Aalbaek B, et al. Biocompatibility of an enzyme-based electrochemical glucose sensor for short-term implantation in the subcutis [J]. Diabetes Technol Ther, 2006, 8(5): 546-559. [6] 刘晶,胡杨,沈玉凤,等. 壳聚糖与海藻酸钙双相陶瓷骨支架的机械性能及细胞相容性 [J]. 中国组织工程研究, 2016, 20(8): 1104-1110. [7] Wang Ning, Burugapalli K, Song Wenhui, et al. Electrospun fibro-porous polyurethane coatings for implantable glucose biosensors [J]. Biomaterials, 2013, 34(4): 888-901. [8] Wang Ning, Burugapalli K, Wijesuriya S, et al. Electrospun polyurethane-core and gelatin-shell coaxial fibre coatings for miniature implantable biosensors [J]. Biomaterials, 2014, 6(1): 015002. [9] Wang Yan, Papadimitrakopoulos F, Burgess DJ. Polymeric “smart” coatings to prevent foreign body response to implantable biosensors [J]. Journal of Controlled Release, 2013, 169(3): 341-347. [10] Vaddiraju S, Legassey A, Qiang Liangliang, et al. Enhancing the sensitivity of needle-implantable electrochemical glucose sensors via surface rebuilding [J]. Journal of Diabetes Science and Technology, 2013, 7(2): 441-451. [11] Koh A, Lu Yuan, Schoenfisch MH. Fabrication of nitric oxide-releasing porous polyurethane membranes-coated needle-type implantable glucose biosensors [J]. Anal Chem, 2013, 85(21): 10488-10494. [12] Bruggeman LA, Doan RP, Loftis J, et al. A cell culture system for the structure and hydrogel properties of basement membranes; Application to capillary walls [J]. Cell Mol Bioeng, 2012, 5(2): 194-204. [13] Hsiao YC, Yang TL. Data supporting chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components [J]. Data in Brief, 2015, 17(4): 551-558. [14] Fang L, Liang B, Yang G, et al. Study of glucose biosensor lifetime improvement in 37℃ serum based on PANI enzyme immobilization and PLGA biodegradable membrane. [J]. Biosensors and Bioelectronics, 2014, 15(56): 91-96. [15] 戴云,伺静,吴方. 基底膜基质/壳聚糖诱导骨髓间充质干细胞成软骨分化 [J]. 中国组织工程研究, 2015, 19(10): 1506-1510. [16] Klueh U, Antar O, Czajkowski C, Ludzinska I, et al. Basement Membrane-Based Glucose Sensor Coatings Enhance Continuous Glucose Monitoring in Vivo [J]. Journal of Diabetes Science and Technology, 2015, 9(5): 957-965. [17] 黄玉芬,邹励宏,高洁,等. 烷基化壳聚糖的制备及止血效果 [J]. 中国组织工程研究, 2016, 20(52): 7878-7884. [18] 秦颖哲,林强. 壳聚糖水凝胶在生物医学材料方面的研究进展 [J]. 中国组织工程研究, 2012, 16(34): 6389-6392. [19] Sharkawy AA, Klizman B, Truskey GA, et al. Engineering the tissue which encapsulates subcutances implants. III. Effective tissue response times [J]. J Biomed Mater Res, 1998, 40(4): 586-605. [20] Ju Youngmin, Yu Bazhang, West L, et al. A novel porous collagen scaffold around an implantable biosensor for improving biocompatibility [J]. J Biomed Mater Res, 2010, 92(2): 650-658. [21] Norton LW, Tegnell E, Toporek SS, et al. In vitro characterization of vascular endothelial growth factor and dexamethasone releasing hydrogels for implantable probe coatings [J]. Biomaterials, 2005, 26(16): 3285-3297. [22] Theresa AH, Yasuhiko T, Antonios GM. In vitro release of transforming growth factor-b1 from gelatin microparticles encapsulated in biodegradable, injectable oligo (poly (ethylene glycol) fumarate) hydrogels [J]. Journal of Controlled Release, 2003, 3(91): 299-313. [23] Xue Lian, Greisler HP. Effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system [J]. Surgery, 2002, 132(2): 259-267. [24] Vegas AJ, Veiseh O, Gürtler M, et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice [J]. Nature Medicine, 2016, 22(3): 306-311. [25] Vegas AJ, Veiseh O, Doloff JC, et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates [J]. Nature Biotechnology, 2016, 34(6): 345-352. |
[1] |
Li Xiaojing ,Gao Bo, Dong Yan ,Gou Zhongru, Miao Yuwen. Effect of Electrospun Collagen/Chitosan Composite Nanofibrous Membrane on Osteogenesis for Bone Regeneration[J]. Chinese Journal of Biomedical Engineering, 2018, 37(1): 79-85. |
[2] |
Zhang Chi, Li Mei, Zhao Jiyuan. Research Progress on Extracellular Matrix Materials in Bone Tissue Engineering[J]. Chinese Journal of Biomedical Engineering, 2017, 36(1): 103-108. |
|
|
|
|