Preparation and Release Performance in Vitro of Chitosan Microspheres/nHA/PLGA Compound Scaffolds

作者: 白 燕 , 肖 唯 :重庆医科大学药学院,重庆;

关键词: 壳聚糖羟基乙酸复合支架控释Chitosan Poly Lactic-Co-Glycolic Acid Composite Scaffolds Controlled Release

本研究以胰蛋白酶(Try)为模型蛋白,将壳聚糖缓释微球与可降解多孔支架复合,构建可次第释放不同生长因子的骨组织工程支架。首先,制备载胰蛋白酶的壳聚糖微球(Try-CMs),然后将微球与纳米羟基磷灰石/羟基乙酸(nHA/PLGA)按照一定的比例混合,通过粒子沥虑–冷冻干燥复合工艺制备Try-CMs/ nHA/PLGA复合支架。结果表明,制备的Try-CMs呈规则球形,粒径分布在4~10 μm之间,胰蛋白酶包封率为61.33%,载药量为25.69%。制备的Try-CMs/nHA/PLGA复合支架孔径为100~200 μm,孔隙率为53.24%,抗压强度为7.31 MPa,8周降解率为19.92%。48 h,Try-nHA/PLGA、Try-CMs、Try-CMs/nHA/ PLGA复合支架累计释放率分别57.31%、69.32%和26.03%;14天时,Try-nHA/PLGA、Try-CMs和Try-CMs/nHA/PLGA复合支架的累计释放率分别为77.89%、85.73%和54.53%。Try-CMs/nHA/PLGA复合支架对蛋白药物具有良好的缓释作用,有望作为具有蛋白类药物缓释作用的组织工程支架。

Abstract: In order to construct a bone regeneration scaffold that different growth factors controlled release at proper stage, Trypsin (Try) was selected as the model protein. The composite of sustained-re- lease microspheres and biodegradable porous scaffolds was prepared in this study. Firstly, Tryp-sin-chitosan microspheres (CMs) were prepared. Then, Trypsin-CMs were compounded to the nano hydroxyapatite/poly lactic-co-glycolic acid (nHA/PLGA) to build a scaffold that could release growth factors sequentially. The results showed that the Try-CMs were spherical shape with diameters of 4 - 10 μm. The encapsulation efficiency of the Trypsin in CMs was 61.33%, and the loading capacity was 25.699%. The prepared Try-CMs/nHA/PLGA scaffold possessed 100 - 200 μm pore diameter, 53.24% porosity, 7.31 MPa compressive strength, and 19.92% degradation at 8 weeks. The cumulative releases of Trypsin from Try-nHA/PLGA, Try-CMs and Try-CMs/nHA/PLGA scaffolds were respectively about 57.31%, 69.32% and 26.03% at 48 hours, 77.89%, 85.73% and 54.53% at 14 days. The results demonstrated that Try-CMs/nHA/PLGA scaffolds had excellent drug sustained-release performance, which would be used as tissue engineering scaffolds with protein controlled delivery.

文章引用: 白 燕 , 肖 唯 (2016) CMs/nHA/PLGA复合支架的制备及体外释放性能的研究。 材料科学, 6, 256-262. doi: 10.12677/MS.2016.64033


[1] Deschaseaux, F., Sensébé, L. and Heymann, D. (2009) Mechanisms of Bone Repair and Regeneration. Trends in Molecular Medicine, 15, 417-429.

[2] Nakano, K., Murata, K., Omokawa, S., et al. (2016) Promo-tion of Osteogenesis and Angiogenesis in Vascularized Tissue-Engineered Bone Using Osteogenic Matrix Cell Sheets. Plastic & Reconstructive Surgery, 137, 1476-1484.

[3] Kanczler, J.M., Ginty, P.J., White, L., et al. (2010) The Effect of the Delivery of Vascular Endothelial Growth Factor and Bone Morphogenic Protein-2 to Osteoprogenitor Cell Populations on Bone Formation. Biomaterials, 31, 1242- 1250.

[4] Wang, Q., Hua, Q. and Wang, S. (2007) Application of Fibrin Glue in Facial Nerve Repair. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 24, 612-614.

[5] Thevenot, P.T., Nair, A.M., Shen, J.H., Lotfi, P., Ko, C.-Y. and Tang, L.P. (2010) The Effect of Incorporation of SDF- 1α into PLGA Scaffolds on Stem Cell Recruitment and the Inflammatory Response. Biomaterials, 31, 3997-4008.

[6] Ambrosio, A.M., Sahota, J.S. and Khan, Y. (2001) A Novel Amor-phous Calcium Phosphate Polymer Ceramic for Bone Repair: I. Synthesis and Characterization. Journal of Biomedical Materials Research, 58, 295-301.<295::AID-JBM1020>3.0.CO;2-8

[7] 赵君, 蒋欣泉, 张志愿. 羟磷灰石/聚乙丙交酯生物复合材料的研究进展[J]. 国际口腔医学杂志, 2008, 35(2): 207- 209.

[8] 安世昌, 孙健, 李亚莉等. 复合壳聚糖纳米微球聚乳酸–羟基乙酸/纳米羟基磷灰石缓释载体系统对蛋白的缓释作用[J]. 中国组织工程研究与临床康复, 2011, 15(25): 4615-4618.

[9] Bai, Y., Yin, G.F., Huang, Z.B., et al. (2013) Localized Delivery of Growth Factors for Angiogenesis and Osteogenesis in Tissue Engineering. International Immunopharmacology, 2, 214-223.

[10] Maekawa, T. (2011) Polymeric Scaffolds in Tissue Engineering Application: A Review. International Journal of Polymer Science, 2011, 609-618.

[11] Sun, Y., Wang, J., Feng, Z., et al. (2016) The Preparation and Characteristics of Spray Dried Astragalus Polysaccharides/Chitosan Microspheres for Pulmonary Drug Delivery. Nanomedicine Nanotechnology Biology & Medicine, 12, 565-565.

[12] Morille, M., Toupet, K., Montero-Menei, C.N., et al. (2016) PLGA-Based Microcarriers Induce Mesenchymal Stem Cell Chondrogenesis and Stimulate Cartilage Repair in Osteoarthritis. Biomaterials, 88, 60-69.

[13] Cui, H.X., Guo, J., Han, Z., et al. (2015) Biocompatibility of Differ-ently Proportioned HA/PLGA/BMP-2 Composite Biomaterials in Rabbits. Genetics & Molecular Research GMR, 14, 13511-13518.