携载BMP-2的PLGA缓释微球的制备及其成骨活性的研究

摘要
图/表
参考文献(20)
相关文章 (0)

全文: PDF (885 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的以聚乳酸-聚乙醇酸（PLGA）制备新型缓释载药微球，携载骨生长因子2（BMP-2），研究其物理学特性以及在体内、体外对成骨的影响。方法采用复合复乳法制备载有BMP-2的PLGA缓释微球，检测形态、粒径、载药率、包封率、释药规律。观察其在体外环境下对骨髓间充质干细胞（BMSCs）增殖分化的影响，观察其在小鼠股部肌肉内异位成骨的情况。结果缓释微球的表面光滑，平均粒径为（242.2±31.3）μm，正态分布，微球的体外释药规律符合双相动力学释药规律。随着微球缓释量的增加，携载BMP-2的微球组细胞增殖明显加快（P < 0.05），BMP-2介导的BMSCs增殖呈浓度依赖性升高（P < 0.05）。微球体内成骨效果明显，4周后可见大量的骨小梁，并有骨髓腔形成。结论携载BMP-2的PLGA缓释微球具有良好的载药特性，可明显促进BMSCs增殖、分化、提高成骨活性。在骨组织工程研究中具有广阔的应用前景。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	吴永恒张孜君黄岩赵文

关键词 ：聚乳酸-聚乙醇酸, 人骨形成蛋白, 微球载体, 成骨活性, 骨组织工程

Abstract：Objective To research the physical characteristics of novel bone morphogenetic factor-2 (BMP-2)-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres with a sustained control release of BMP-2 for bone induction and the influence ossification in vitro and in vivo. Methods The BMP-2-loaded PLGA microspheres through double emulsion method was prepared, and the physiological properties of microspheres was investigated, including particle size and loading and encapsulation rates of BMP-2, and the release profile of BMP-2. The effects of BMP-2-loaded microspheres on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro and the ectopic bone formation inside the mouse thigh muscle were studied. Results The average size of PLGA particles loaded with BMP-2 was (242.2±31.3) μm with smooth surface. BMP-2 released from microspheres displayed a biphasic release profile. BMSCs cultured with BMP-2-loaded microspheres showed the fastest proliferation rate among all groups (P < 0.05). The proliferation rate of BMSCs was dose-dependent on BMP-2 (P < 0.05). Ectopic bone formation in the mouse thigh muscle was observed after injection of BMP-2-loaded-microspheres. A large number of trabecular bone appeared with emerging bone marrow cavity 4 weeks after the injection. Conclusion The new method to prepare PLGA microspheres loaded with BMP-2 has a sustained control release rate, which can promote the proliferation and differentiation of BMSCs in vitro and ectopic bone formation in vivo. BMP-2-loaded PLGA microsphere holds high potential for wide application in bone tissue regeneration.

Key words： PLGA BMP-2 Microspheres Osteogenetic activity Bone tissue

通讯作者: 赵文（1968.10-），男，博士，主任医师；研究方向：骨与关节创伤。

引用本文:

吴永恒张孜君黄岩赵文. 携载BMP-2的PLGA缓释微球的制备及其成骨活性的研究[J]. 中国医药导报, 2017, 14(23): 25-28.
WU Yongheng ZHANG Zijun HUANG Yan ZHAO Wen. Study on preparation and osteogenic effects of BMP-2-loaded PLGA microspheres with a sustained control release. 中国医药导报, 2017, 14(23): 25-28.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2017/V14/I23/25

[1] Yu NY，Schindeler A，Little DG，et al. Biodegradable poly（alpha-hydroxy acid） polymer scaffolds for bone tissue engineering [J]. J Biomed Mater Res B Appl Biomater，2010， 93（1）：285-295.
[2] Saito N，Murakami N，Takahashi J，et al. Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins [J]. Adv Drug Deliv Rev，2005，57（7）：1037-1048.
[3] Ji Y，Xu GP，Zhang ZP，et al. BMP-2/PLGA delayed-release microspheres composite graft，selection of bone particulate diameters，and prevention of aseptic inflammation for bone tissue engineering [J]. Ann Biomed Eng，2010，38（3）：632-639.
[4] Minier K，Toure A，Fusellier M，et al. BMP-2 delivered from a self-crosslinkable CaP/hydrogel construct promotes bone regeneration in a critical-size segmental defect model of non-union in dogs [J]. Vet Comp Orthop Traumatol，2014，27（6）：411-421.
[5] Kempen DH，Lu L，Heijink A， et al. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration [J]. Biomaterials，2009，30（14）：2816-2825.
[6] Lee SC，Shea M，Battle MA， et al. Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA matrix [J]. J Biomed Mater Res，1994，28（10）：1149-1156.
[7] Holland TA，Tabata Y，Mikos AG. In vitro release of transforming growth factor-beta 1 from gelatin microparticles encapsulated in biodegradable，injectable oligo[poly（ethylene glycol） fumarate] hydrogels [J]. J Control Release，2003，91（3）：299-313.
[8] Holland TA，Tessmar JK，Tabata Y，et al. Transforming growth factor-beta 1 release from oligo[poly（ethylene glycol） fumarate] hydrogels in conditions that model the cartilage wound healing environment [J]. J Control Release，2004， 94（1）：101-114.
[9] Mundargi RC，Babu VR，Rangaswamy V，et al. Nano/micro technologies for delivering macromolecular therapeutics using poly（D，L-lactide-co-glycolide） and its derivatives [J]. J Control Release，2008，125（3）：193-209.
[10] Lee JH，Baek HR，Lee KM，et al. Effects of ovariectomy and corticosteroid-induced osteoporosis on the osteoinductivity of rhBMP-2 in a segmental long-bone defect model [J]. Tissue Eng Part A，2015，21（15-16）：2262-2271.
[11] Yasko AW，Lane JM，Fellinger EJ，et al. The healing of segmental bone defects，induced by recombinant human bone morphogenetic protein （rhBMP-2）. A radiographic，histological，and biomechanical study in rats [J]. J Bone Joint Surg Am，1992，74（5）：659-670.
[12] Jeon O，Song SJ，Yang HS ，et al. Long-term delivery enhances in vivo osteogenic efficacy of bone morphogenetic protein-2 compared to short-term delivery [J]. Biochem Biophys Res Commun，2008，369（2）：774-780.
[13] Higuchi T，Kinoshita A，Takahashi K，et al. Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling [J]. J Periodontol，1999，70（9）：1026-1031.
[14] Peng KT，Hsieh MY，Lin CT，et al. Treatment of critically sized femoral defects with recombinant BMP-2 delivered by a modified mPEG-PLGA biodegradable thermosensitive hydrogel [J]. BMC Musculoskelet Disord，2016，17：286.
[15] Holland TA，Tabata Y，Mikos AG. Dual growth factor delivery from degradable oligo[poly（ethylene glycol） fumarate] hydrogel scaffolds for cartilage tissue engineering [J]. J Control Release，2005，101（1-3）：111-125.
[16] Zhang HX，Zhang XP，Xiao GY ，et al. In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head [J]. Mater Sci Eng C Mater Biol Appl，2016 ，60：298-307.
[17] Luca L，Rougemont AL，Walpoth BH，et al. The effects of carrier nature and pH on rhBMP-2-induced ectopic bone formation [J]. J Control Release，2010，147（1）：38-44.
[18] Maiti SK，Ninu AR，Sangeetha P，et al.Mesenchymal stem cells-seeded bio-ceramic construct for bone regeneration in large critical-size bone defect in rabbit [J]. J Stem Cells Regen Med，2016，12（2）：87-99.
[19] Inoda H，Yamamoto G，Hattori T. Histological investigation of osteoinductive properties of rh-BMP2 in a rat calvarial bone defect model [J]. J Craniomaxillofac Surg，2004，32（6）：365-369.
[20] Inoda H，Yamamoto G，Hattori T. rh-BMP2-induced ectopic bone for grafting critical size defects：a preliminary histological evaluation in rat calvariae [J]. Int J Oral Maxillofac Surg，2007，36（1）：39-44.