Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (18): 2936-2940.doi: 10.3969/j.issn.2095-4344.1712
Previous Articles Next Articles
Received:
2019-01-22
Online:
2019-06-28
Published:
2019-06-28
Contact:
Liu Yi, Professor, Master’s supervisor, First Department of Orthopedics, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
About author:
Zhang Jun, Master candidate, First Department of Orthopedics, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
CLC Number:
Zhang Jun, You Qi, Zou Gang, Ge Zhen, Liu Yi. Application and progress of strontium in bone tissue engineering[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(18): 2936-2940.
2.1 锶的一般特性 2.1.1 锶的分布 锶是人体的必须微量元素,人体内含有大约320 mg锶,其中约90%以上的锶存在于骨骼中,仅很少一部分分布于细胞外液,它是牙齿和骨骼的主要组成成分,参与骨的形成[15]。在元素周期表中,锶元素与钙属于同一族,因此两者化学性质极其相似,且均为亲骨性元素。锶作为Ca2+激动剂,能激活Ca2+通道,参与体内各种生化过程,但其作用效果较Ca2+弱[16]。锶有多种同位素,其中89Sr、90Sr具有一定的放射性,临床上经常用于骨骼系统肿瘤及骨转移瘤的放疗,两者的治疗效果和作用原理有一定不同:89Sr是通过杀死癌细胞减轻癌症患者的骨痛症状[17];90Sr主要在血管瘤治疗方面有较好的效果,它主要是通过抑制增生的血管瘤细胞和分化较差的血管瘤细胞来发挥作用的[18]。 锶是与钙密切相关的代谢微量元素,锶离子主要通过2种机制进入骨中:①快速摄取机制:该过程取决于成骨细胞的活性,通过与Ca2+的交换过程或与骨样蛋白结合,Sr2+被吸收进入骨组织;②Sr2+结合到骨矿物相的晶格中[19-20]:当Sr2+的存在水平高于正常细胞生理学所需的水平时,它会通过激活不同的细胞途径来诱导对骨骼的药理作用[19-20]。 2.1.2 锶的吸收 人体锶的主要来源是经食物摄取,然后经过消化道吸收,少部分锶是经过皮肤吸收的[21]。影响锶吸收的因素很多,例如:胃肠道功能、微生素D含量及年龄[22]。有学者认为随着年龄的增加,锶的吸收逐渐减少,但也有人认为锶的吸收与年龄和性别无关[23]。由于锶和钙属于同一族元素,所以其化学性质和生理性能与钙极其相似,其吸收方式、载体也与钙类似。但与钙不同的是,锶的吸收能力和量极其微弱,仅为钙的 1/2 [24]。关于锶吸收方式的研究也较多,但尚未得出统一的结论,有研究者认为锶在消化道的吸收完全是通过被动扩散的,但也有人认为其吸收既有被动扩散又有主动运输。当小肠内锶的浓度较高时,其吸收方式是不需要耗能的被动扩散;当其浓度较低时,是通过逆浓度梯度的耗能主动运输方式吸收的[25-26]。 2.1.3 锶的排泄 血中的锶大部分(约96%)是由肾脏经尿液排泄的,仅有一少部分是通过胃肠道排泄的。因此,肾功能受损或者肾功能不全的患者,极易引起锶在体内的过度积蓄,从而产生不良后果。此外,肾小管对锶的重吸收小于钙,并且对锶的排泄远远大于钙[27]。 2.2 锶的成骨作用机制 骨的形成和骨折后的修复愈合是一个多因子、多细胞参与的复杂过程,涉及了很多的信号分子通路,也是成骨细胞和破骨细胞同时参与的一个动态平衡过程。锶能促进成骨细胞分化的同时抑制破骨细胞的吸收,这已是当今比较公认的一大观点,目前也有大量体内外研究证实了该观点[28],但是锶具体是如何介导成骨效应的目前还不清楚,有很多种假说和不同的结论。以往的研究结果提示,锶能够激活不同的信号通路,从而作用于成骨细胞及破骨细胞,在分子和细胞水平调节骨的形成,增加骨质密度,改善骨的微结构,进而促进骨的修复。此外,锶还能够作用于前成骨细胞,促进其增殖和分化,进而促进骨的修复。 钙敏感受体是一种G蛋白偶联受体,广泛存在于骨细胞(成骨细胞、破骨细胞和骨细胞)的细胞膜上,该受体与细胞外的二价阳离子具有一定的亲和力,如钙离子和锶离子,细胞外的信号分子通过激活或者抑制该信号通路来诱导细胞内的反应[29]。研究发现,细胞外的钙离子可通过激活钙敏感受体来促进骨髓间充质干细胞的增殖和成骨分化,由此得出钙敏感受体在介导骨髓间充质干细胞成骨分化中起到的一定的作用[30]。与钙类似,研究发现锶也能够激活钙敏感受体,进一步激活肌醇-1,4,5-三磷酸(IP3)的产生和MAPK信号传导,这些研究表明锶同样可通过钙敏感受体途径促进成骨分化[28]。Brennan等[31]研究发现,锶通过作用于钙敏感受体促进成骨细胞的增殖分化并延长其寿命,同时锶还通过钙敏感受体抑制破骨细胞相关分子和蛋白的表达,证实了锶是通过钙敏感受体途径来促进成骨分化和抑制破骨细胞的。 Wnt信号通路被证实在调控细胞增殖分化过程中有着极其重要的作用,可分为经典途径和非经典途径2 类,经典的Wnt通路即Wnt/β-catenin信号通路,非经典 Wnt途径包括 Wnt/Jnk信号通路和Wnt/Ca2+信号通 路[32]。研究已证明,Wnt信号传导途径在调节干细胞体内成骨分化和细胞外基质合成中起重要作用[33]。Yang等[34]研究表明,锶能够显著增加β-catenin的表达,一方面,锶可增加β-连环蛋白和Frizzed受体的表达,从而转导激活下游成骨转录因子并增强成骨细胞分化的信号;另一方面,锶还可抑制Wnt通路抑制剂的表达,阻止β-连环蛋白的降解,促进成骨分化。 2.3 锶在骨组织工程中的应用 天然骨的无机成分主要以羟基磷灰石为主,但将体外以羟基磷灰石为原料构建的组织工程骨移植到体内修复骨缺损时,却不能达到令人满意的效果。不仅如此,其他材料构建的组织工程骨也未能取得满意的效果,目前尚未寻找到一个比较理想的材料,因此学者将目光转移到对材料的改性上面。锶作为一种能够促进成骨细胞合成和代谢的亲骨元素,将其加入到骨组织工程支架材料中,改善原有骨替代材料的性能,取得了一定的成绩。 张文等[35]将锶掺杂入微纳米生物活性玻璃中,制备出0%,5%,10%和15%4个不同浓度梯度的掺锶微纳米生物活性玻璃,通过体内外实验来研究不同浓度掺锶微纳米生物活性玻璃对小鼠巨噬细胞从MI向M2极化的影响,以及极化后对小鼠骨髓间充质干细胞成骨分化的影响,实验结果发现:不同掺锶量的掺锶微纳米生物活性玻璃,均能够促进小鼠巨噬细胞从M1向M2分化,并且极化后的巨噬细胞能够分泌细胞因子,促进骨髓间充质干细胞成骨分化。Zhou等[36]在微弧氧化微孔TiO2基质上用Sr-羟基磷灰石涂层制备出了2种不同形貌的基质表面(纳米短棒状和纳米颗粒状),并且在其表面培养人胚胎成骨细胞,实验结果显示:实验组细胞成骨分化能力较对照组明显增强,成骨相关标志物如RUNX2、碱性磷酸酶、骨桥蛋白、骨钙蛋白、Ⅰ型胶原等的含量,均随时间的增加呈现上升趋势,并且纳米棒状结构表面涂层的效果较纳米颗粒结构表面涂层更明显。该实验结果提示,Sr-羟基磷灰石能够上调成骨相关基因和蛋白的表达,分泌更多的基质蛋白,加速矿化,且促进成骨分化的效果还与涂层表面形状结构有一定关系。王成 健[37]将锶以SrO的形式与羟基磷灰石掺杂在一起,制备出SrO/羟基磷灰石复合材料,通过对该复合材料力学特性、孔隙率等的检测发现:SrO的掺入,有效改善了羟基磷灰石的力学性能,复合材料的抗压强度大于 335 MPa;在一定程度上改善了羟基磷灰石的降解性能,研究还发现含锶量3%-7%的多孔SrO/羟基磷灰石支架,具有较好的降解性能和更好的矿化能力。Hulsart-Billström等[38]将锶与磷酸钙球复合制备出了一种新型的骨替代材料,即掺锶磷酸钙球,体外实验发现掺锶磷酸钙球具有良好的生物相容性,没有纤维化组织或异物反应的迹象;进一步的体内实验显示,掺锶20%实验组较未掺锶的对照组具有更强的诱导成骨和促进骨修复的作用。该研究与之前其他研究不同的是,通过局部锶的释放而非系统的锶处理来观察其成骨效果,虽然该实验关于来自掺锶磷酸钙球的锶离子释放速率是未知的,但其释放剂量并没有产生毒副反应,同时还能促进骨的修复,表明掺锶磷酸钙球是一种具有应用前景的新型骨替代材料。Catanzano等[39]研究了一种具有多孔和良好互连结构的大孔藻酸盐泡沫支架材料,然后在支架材料中加入锶来改善其机械性能和生物性能,结果发现:不同的锶浓度会影响支架材料的孔隙率和性状,并且随着锶浓度的增加,支架材料在生理条件下更加坚硬和稳定,且呈剂量依赖性;进一步的细胞生物相容性研究发现具有较高锶浓度的支架,能够促进支架上间充质干细胞的增殖与成骨分化能力。 2.4 锶在临床中的应用 骨质疏松症是一种代谢性骨病,其特征是骨转换率高、骨量低、骨微观结构破坏、骨脆性和骨折风险增加[40]。患有骨质疏松症的患者,发生成骨退化和破骨细胞增强,同时成骨细胞功能削弱,导致身体承重部位骨折的风险增加[41]。骨质疏松症女性患者远多于男性患者,因此该病也被认为是一种雌激素缺乏症,因为雌激素缺乏会增加骨重塑的速度,这与负重塑平衡相关,即吸收超过形成,从而导致骨骼的结构、质量和强度受损[41]。此外,其他遗传和表观遗传因素可能在引发骨质疏松症中起重要作用。对于骨质疏松患者,预防骨折是治疗的首要目标。锶的衍生物雷奈酸锶,是临床上比较常见的用于预防和治疗骨质疏松的药物,在欧洲多个国家已获得批准并应用于临床,其主要原理是能够促进骨折愈合和骨整合[42-44]。雷奈酸锶被认为可抑制破骨细胞诱导的骨吸收及破骨细胞活化/分化[45],并刺激成骨细胞的骨形成功能和成骨细胞的增殖/分化能力。最新的研究表明,雷奈酸锶能够增强Ⅰ型胶原和骨桥蛋白的表达,而它们正是有机骨基质的重要组成部 分[46]。此外,雷奈酸锶能够促进成骨培养物中大骨样结节的形成并加速前成骨细胞中成骨细胞表型的表达[46]。基于以上基础研究和理论,大量临床研究也进一步证实了系统性雷奈酸锶治疗,可最大限度地减少多发性绝经后骨质疏松症女性椎骨、非椎骨和髋部骨折的风险[47-48]。"
[1]Wu C, Chang J. Multifunctional mesoporous bioactive glasses for effective delivery of therapeutic ions and drug/growth factors. J Control Release.2014;193:282-295.[2]Merli M,Moscatelli M,Mariotti G,et al.Autogenous bone versus deproteinised bovine bone matrix in 1-stage lateral sinus floor elevation in the severely atrophied maxilla: a randomised controlled trial. Eur J Oral Implantol.2013;6(1):27-37.[3]Terheyden H,Jepsen S,Moller B,et al.Sinus floor augmentation with simultaneous placement of dental implants using a combination of deproteinized bone xenografts and recombinant human osteogenic protein-1.A histometric study in miniature pigs. Clin Oral Implants Res.1999;10(6):510-521.[4]Spin-Neto R,Stavropoulos A,Coletti FL,et al.Remodeling of cortical and corticocancellous fresh-frozen allogeneic block bone grafts--a radiographic and histomorphometric comparison to autologous bone grafts.Clin Oral Implants Res.2015;26(7):747-752.[5]Aroni MAT,de Oliveira GJPL,Spolidório LC,et al.Loading deproteinized bovine bone with strontium enhances bone regeneration in rat calvarial critical size defects.Clin Oral Investig. 2018. doi: 10.1007/s00784-018-2588-6.[Epub ahead of print][6]Kotsakis GA,Salama M,Chrepa V,et al.A randomized, blinded, controlled clinical study of particulate anorganic bovine bone mineral and calcium phosphosilicate putty bone substitutes for socket preservation. Int J Oral Maxillofac Implants. 2014;29(1): 141-151.[7]Toloue SM,Chesnoiu-Matei I, Blanchard SB,et al. A clinical and histomorphometric study of calcium sulfate compared with freeze-dried bone allograft for alveolar ridge preservation.J Periodontol. 2012;83(7):847-855.[8]Tal H.Autogenous masticatory mucosal grafts in extraction socket seal procedures: a comparison between sockets grafted with demineralized freeze-dried bone and deproteinized bovine bone mineral. Clin Oral Implants Res.1999;10(4):289-296.[9]Daly AC,Freeman FE,Gonzalezfernandez T,et al.3D Bioprinting for Cartilage and Osteochondral Tissue Engineering.Adv Healthc Mater. 2017;6(22):1-20.[10]Hermanson O.Advances in tissue engineering.Acta Pædiatrica. 2010; 98(10):1699-1699.[11]Martínez-Vázquez FJ,Cabañas MV, Paris JL,et al.Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration.Acta Biomater. 2015;15:200-209.[12]Cui W, Sun G, Qu Y,et al.Repair of rat calvarial defects using Si-doped hydroxyapatite scaffolds loaded with a bone morphogenetic protein-2-related peptide.J Orthop Res. 2016;34(11): 1874-1882.[13]Agarwal R,García AJ.Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv Drug Deliv Rev.2015;94:53-62.[14]苏文婷,初晓辉,谷大海,等.锶与骨质疏松症[J].微量元素与健康研究, 2011,28(1):63-65.[15]梁永强,胡敏.掺锶复合材料对骨形成影响的研究进展[J].中华老年口腔医学杂志,2014,12(1):37-40.[16]Coulombe J,Faure H,Robin BM,et al.In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor. Biochem Biophys Res Commun.2004;323(4):1184-1190.[17]谢玲,裴志东,薛琪,等.锶治疗骨转移性癌痛的临床观察[J].中国乡村医药,2008,15(5):19-20.[18]祁岗,于梅花,朱艳媚,等.锶敷贴器治疗皮肤血管瘤疗效观察[J].新医学, 2011,42(4):260-262.[19]Scardueli CR,Bizelli-Silveira C,Marcantonio RAC,et al. Systemic administration of strontium ranelate to enhance the osseointegration of implants: systematic review of animal studies. Int J Implant Dent.2018;4(1):21.[20]Dahl SG,Allain P,Marie PJ,et al.Incorporation and distribution of strontium in bone.Bone. 2001;28(4):446-453.[21]黄祎雯,傅远飞,张保卫,等.锶对骨代谢影响的研究进展[J].中国口腔种植学杂志,2010,15(3):153-156, 164.[22]王亮,张志敏,郭前进,等.雷奈酸锶对骨质疏松症的治疗作用[J].中国实用医刊,2012,39(2):95-96.[23]Zamburlini M,Campbell JL, de Silveira G, et al.Strontium depth distribution in human bone measured by mieroPlxE.X-Ray Spectrom.2009;38:271-277.[24]Milsom S,Ibbertson K,Hannan S,et al.Simple test of intestinal calcium absorption measured by stable strontium. Br Med J (Clin Res Ed).1987;295(6592):231-234.[25]DUMONT PA,CURRAN PF,SOLOMON AK,et al.Calcium and strontium in rat small intestine: Their fluxes and their effect on Na flux.J Gen Physiol.1960;43(7):1119-1136.[26]杨玲,殷晓进.锶与骨矿代谢[J].中国骨质疏松杂志, 2003,10(3): 384-387. [27]陈兵,赵婷婷,王海萍,等.血液透析患者外周血铅、镉、锶、铝水平研究[J].中华肾脏病杂志,2013,29(2):152-153. [28]Pilmane M,Salma-Ancane K,Loca D,et al.Strontium and strontium ranelate: Historical review of some of their functions.Mater Sci Eng C Mater Biol Appl. 2017;78:1222-1230. [29]Conigrave AD,Ward DT.Calcium-sensing receptor (CaSR): pharmacological properties and signaling pathways. Clin Endocrinol Metab.2013;27(3):315-331.[30]Gonzalez-Vazquez A,Planell JA, Engel E, et al. Extracellular calcium and CaSR drive osteoinduction in mesenchymal stromal cells. Acta Biomaterialia, 2014, 10(6):2824-2833.[31]Brennan TC,Rybchyn MS,Green W,et al.Osteoblasts play key roles in the mechanisms of action of strontium ranelate.Br J Pharmacol. 2009;157(7):1291-1300.[32]Angers S,Moon RT.Proximal events in Wnt signal transduction.Nat Rev Mol Cell Biol.2009; 10(7):468-477.[33]Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006; 127(3):469-480.[34]Yang F,Yang D, Tu J, et al.Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling.Stem Cells. 2011; 29(6):981-991.[35]张文,黄德球,郭周义,等.掺锶生物活性玻璃通过调控巨噬细胞极化促进成骨[J].激光生物学报,2018, 27(3):232-239. [36]Zhou J,Li B, Lu S,et al.Regulation of osteoblast proliferation and differentiation by interrod spacing of Sr-HA nanorods on microporous titania coatings.Acs Appl Mater Interfaces.2013; 5(11): 5358-5365.[37]王成健.多孔SrO/HA生物复合陶瓷骨修复材料的制备及体外生物相容性研究[D].昆明:昆明理工大学,2016.[38]Hulsart-Billström G,Wei X,Pankotai E,et al.Osteogenic potential of Sr‐doped calcium phosphate hollow spheres in vitro and in vivo.J Biomed Mater Res A. 2013;101(8):2322-2331. [39]Catanzano O,Soriente A,La Gatta A,et al.Macroporous alginate foams crosslinked with strontium for bone tissue engineering. Carbohydr Polym.2018;202:72-83.[40]Curtis EM,Moon RJ,Dennison EM,et al.Recent advances in the pathogenesis and treatment of osteoporosis. Clin Med (Lond). 2015; 15(6):92-96.[41]Marie PJ,Felsenberg D,Brandi ML,et al.How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis.Osteoporos Int. 2011;22(6):1659-1667.[42]Blake GM,Lewiecki EM,Kendler DL,et al. A review of strontium ranelate and its effect on DXA scans. J Clin Densitom. 2007;10(2): 113-119.[43]Cianferotti L,D'Asta F, Brandi ML,et al.A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis.Ther Adv Musculoskelet Dis.2013; 5(3):127-139.[44]Kyllönen L,D’Este M,Alini M,et al.Local drug delivery for enhancing fracture healing in osteoporotic bone.Acta Biomaterialia. 2015;11(1): 412-434.[45]Baron R, Tsouderos Y. In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation.Eur J Pharmacol.2002;450(1):11-17.[46]Boivin G,Doublier A,Farlay D.Strontium ranelate -a promising therapeutic principle in osteoporosis. J Trace Elem Med Biol. 2012;26(2-3):153-156.[47]Reginster JY, Seeman E, De Vernejoul MC, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab. 2005;90(5):2816-2822.[48]Roux C, Fechtenbaum J, Kolta S, et al.Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis.Ann Rheum Dis.2008;67(12):1736-1738. |
[1] | Wu Zijian, Hu Zhaoduan, Xie Youqiong, Wang Feng, Li Jia, Li Bocun, Cai Guowei, Peng Rui. Three-dimensional printing technology and bone tissue engineering research: literature metrology and visual analysis of research hotspots [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 564-569. |
[2] | Liu Liu, Zhou Qingzhu, Gong Zhuo, Liu Boyan, Yang Bin, Zhao Xian. Characteristics and manufacturing techniques of collagen/inorganic materials for constructing tissue-engineered bone [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 607-613. |
[3] | Li Xiaozhuang, Duan Hao, Wang Weizhou, Tang Zhihong, Wang Yanghao, He Fei. Application of bone tissue engineering materials in the treatment of bone defect diseases in vivo [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(4): 626-631. |
[4] | Xing Hao, Zhang Yonghong, Wang Dong. Advantages and disadvantages of repairing large-segment bone defect [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(3): 426-430. |
[5] | Yang Caihui, Liu Qicheng, Dong Ming, Wang Lina, Zuo Meina, Lu Ying, Niu Weidong. Serine/threonine protein kinases can promote bone destruction in mouse models of chronic periapical periodontitis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(23): 3654-3659. |
[6] | Zhou Anqi, Tang Yufei, Wu Bingfeng, Xiang Lin. Designing of periosteum tissue engineering: combination of generality and individuality [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(22): 3551-3557. |
[7] | Huo Hua, Cheng Yuting, Zhou Qian, Qi Yuhan, Wu Chao, Shi Qianhui, Yang Tongjing, Liao Jian, Hong Wei. Effects of drug coating on implant surface on the osseointegration [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(22): 3558-3564. |
[8] | Chen Song, He Yuanli, Xie Wenjia, Zhong Linna, Wang Jian. Advantages of calcium phosphate nanoparticles for drug delivery in bone tissue engineering research and application [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(22): 3565-3570. |
[9] | Zhang Zhenhua, Liu Zichen, Yu Baoqing. Status and problems of polycaprolactone and its composite materials in bone tissue engineering [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(22): 3571-3577. |
[10] | Jiang Shengyuan, Li Dan, Jiang Jianhao, Shang-you Yang, Yang Shuye. Biological response of Co2+ to preosteoblasts during aseptic loosening of the prosthesis [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(21): 3292-3299. |
[11] | Xu Hui, Kang Bingxin, Zhong Sheng, Gao Chenxin, Zhao Chi, Qiu Guowei, Sun Songtao, Xie Jun, Xiao Lianbo, Shi Qi. Pressing local acupoints plus adjustion of the knee joint in a sitting position for treating knee osteoarthritis: a randomized controlled trial [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(2): 216-221. |
[12] | Wei Qin, Zhang Xue, Ma Lei, Li Zhiqiang, Shou Xi, Duan Mingjun, Wu Shuo, Jia Qiyu, Ma Chuang. Platelet-derived growth factor-BB induces the differentiation of rat bone marrow mesenchymal stem cells into osteoblasts [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(19): 2953-2957. |
[13] | Guo Zhibin, Wu Chunfang, Liu Zihong, Zhang Yuying, Chi Bojing, Wang Bao, Ma Chao, Zhang Guobin, Tian Faming. Simvastatin stimulates osteogenic differentiation of bone marrow mesenchymal stem cells [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(19): 2963-2968. |
[14] | Wang Liu, Song Dongzhe, Huang Dingming. Bone morphogenetic protein 9 regulates stem cell differentiation and bone regeneration [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(19): 3064-3070. |
[15] | Wang Hongyuan, Wang Wei, Yang Shuqing, Dou Lixin, Liu Lijun. Preparation and properties of porous nitrogen oxygen bioglass scaffold for bone repair [J]. Chinese Journal of Tissue Engineering Research, 2021, 25(16): 2521-2527. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||