张岩;郑欣;朱彦丞;周正楠;张子韬;陈一心;

• 1:南京医科大学鼓楼临床医学院

摘要(Abstract)：

自骨组织工程概念被提出以来,微球材料在骨组织工程技术研究中应用广泛,目前主要在3个方面,分别用于骨组织工程种子细胞的扩增;构建支架材料将细胞传递至骨缺损部位;装载生长因子以诱导骨形成。本文结合国内外研究成果,对微球在骨组织工程中的应用研究进展作一综述。

关键词(KeyWords)： 微球;骨组织工程;支架;种子细胞;载药

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(编号:81401795);; 南京市卫生局一般项目(编号:YKK14076);; 中央高校基本科研业务费项目(编号:20620140712)

作者(Author): 张岩;郑欣;朱彦丞;周正楠;张子韬;陈一心;

Email:

DOI:

参考文献(References)：

• [1]Wang H,Leeuwenburgh SC,Li Y,et al.The use of micro-and nanospheres as functional components for bone tissue regeneration[J].Tissue Eng Part B Rev,2012,18(1):24-39.
• [2]沈士倩,王家伟.微球细胞支架在骨组织工程中的应用[J].中国组织工程研究与临床康复,2009,13(34):6749-6752.
• [3]Salter E,Goh B,Hung B,et al.Bone tissue engineering bioreactors:A role in the clinic[J].Tissue Eng Part B Rev,2012,18(1):62-75.
• [4]Workman VL,Tezera LB,Elkington PT,et al.Controlled generation of microspheres incorporating extracellular matrix fibrils for three-dimensional cell culture[J].Adv Funct Mater,2014,24(18):2648-2657.
• [5]Park JH,Perez RA,Jin GZ,et al.Microcarriers designed for cell culture and tissue engineering of bone[J].Tissue Eng Part B Rev,2013,19(2):172-190.
• [6]Shen S,Fu D,Xu F,et al.The design and features of apatite-coated chitosan microspheres as injectable scaffold for bone tissue engineering[J].Biomed Mater,2013,8(2):025007.
• [7]Mittal A,Negi P,Garkhal K,et al.Integration of porosity and biofunctionalization to form a 3D scaffold:cell culture studies and in vitro degradation[J].Biomed Mater,2010,5(4):045001.
• [8]Park JS,Hong SJ,Kim H Y,et al.Evacuated calcium phosphate spherical microcarriers for bone regeneration[J].Tissue Eng Part A,2010,16(5):1681-1691.
• [9]Bernhardt A,Dittrich R,Lode A,et al.Nanocrystalline spherical hydroxyapatite granules for bone repair:in vitro evaluation with osteoblast-like cells and osteoclasts[J].J Mater Sci Mater Med,2013,24(7):1755-1766.
• [10]Khanna O,Larson JC,Moya ML,et al.Generation of alginate microspheres for biomedical applications[J].J Vis Exp,2012(66):e3388.
• [11]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.
• [12]扈延龄,李红,李树娟,等.复合rh BMP-2壳聚糖微球可注射磷酸钙骨水泥制备及成骨性能研究[J].中国矫形外科杂志,2010,18(20):1723-1726.
• [13]Yang X,Gan Y,Gao X,et al.Preparation and characterization of trace elements-multidoped injectable biomimetic materials for minimally invasive treatment of osteoporotic bone trauma[J].J Biomed Mater Res A,2010,95(4):1170-1181.
• [14]Reverchon E,Cardea S.Supercritical fluids in 3-D tissue engineering[J].J Super Fluids,2012,69(1):97-107.
• [15]Kane RJ,Weiss-Bilka HE,Meagher MJ,et al.Hydroxyapatite reinforced collagen scaffolds with improved architecture and mechanical properties[J].Acta Biomater,2015,17(1):16-25.
• [16]Qutachi O,Vetsch JR,Gill D,et al.Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature[J].Acta Biomater,2014,10(12):5090-5098.
• [17]Li W,Ding Y,Rai R,et al.Preparation and characterization of PHBV microsphere/45S5 bioactive glass composite scaffolds with vancomycin releasing function[J].Mater Sci Eng C Mater Biol Appl,2014,41(41):320-328.
• [18]Amini AR,Adams DJ,Laurencin CT,et al.Optimally porous and biomechanically compatible scaffolds for large-area bone regeneration[J].Tissue Eng Part A,2012,18(13-14):1376-1388.
• [19]Oredein-Mc Coy O,Krogman NR,Weikel AL,et al.Novel factorloaded polyphosphazene matrices:potential for driving angiogenesis[J].J Microencapsul,2009,26(6):544-555.
• [20]Bhamidipati M,Scurto AM,Detamore MS.The future of carbon dioxide for polymer processing in tissue engineering[J].Tissue Eng Part B Rev,2013,19(3):221-232.
• [21]Bhamidipati M,Sridharan B,Scurto AM,et al.Subcritical CO2sintering of microspheres of different polymeric materials to fabricate scaffolds for tissue engineering[J].Mater Sci Eng C Mater Biol Appl,2013,33(8):4892-4899.
• [22]Man Y,Wang P,Guo Y,et al.Angiogenic and osteogenic potential of platelet-rich plasma and adipose-derived stem cell laden alginate microspheres[J].Biomaterials,2012,33(34):8802-8811.
• [23]Jabbarzadeh E,Starnes T,Khan YM,et al.Induction of angiogenesis in tissue-engineered scaffolds designed for bone repair:a combined gene therapy-cell transplantation approach[J].Proc Natl Acad Sci U S A,2008,105(32):11099-11104.
• [24]Turgeman G,Pittman DD,Muller R,et al.Engineered human mesenchymal stem cells:a novel platform for skeletal cell mediated gene therapy[J].J Gene Med,2001,3(3):240-251.
• [25]Roux R,Ladaviere C,Montembault A,et al.Particle assemblies:toward new tools for regenerative medicine[J].Mater Sci Eng C Mater Biol Appl,2013,33(3):997-1007.
• [26]Dormer NH,Gupta V,Scurto AM,et al.Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres[J].Mater Sci Eng C Mater Biol Appl,2013,33(7):4343-4351.
• [27]Liu G,Wu C,Fan W,et al.The effects of bioactive akermanite on physiochemical,drug-delivery,and biological properties of poly(lactide-co-glycolide)beads[J].J Biomed Mater Res B Appl Biomater,2011,96(2):360-368.
• [28]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.
• [29]黄鑫,孟国林,刘建,等.rh-BMP-2壳聚糖微球的制备及体外检测[J].中国矫形外科杂志,2009,17(15):1172-1174.
• [30]Son JS,Appleford M,Ong JL,et al.Porous hydroxyapatite scaffold with three-dimensional localized drug delivery system using biodegradable microspheres[J].J Control Release,2011,153(2):133-140.
• [31]Li B,Yoshii T,Hafeman A E,et al.The effects of rh BMP-2 released from biodegradable polyurethane/microsphere composite scaffolds on new bone formation in rat femora[J].Biomaterials,2009,30(35):6768-6779.
• [32]姚琦,张立海,黄鹏,等.纤维蛋白胶复合重组人骨形态发生蛋白-2微球对犬骨髓基质细胞增殖与分化的影响[J].中国组织工程研究与临床康复,2011,15(42):7873-7876.
• [33]Suliman S,Xing Z,Wu X,et al.Release and bioactivity of bone morphogenetic protein-2 are affected by scaffold binding techniques in vitro and in vivo[J].J Control Release,2015,197:148-157.