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我院研究成果在《ACS Applied Materials & Interfaces》杂志在线发表
时间:[2018-03-26]         阅读:556 次

The Influence of Mussel-Derived Bioactive BMP-2 Decorated PLA on MSCs Behavior in Vitro and Verification with Osteogenicity at Ectopic Sites in Vivo

 

Zhuoyue Chen12, Zhen Zhang1, Juantao Feng1, Yayuan Guo1, Yuan Yu12, Jihong Cui12 Hongmin Li12, Lijun Shang1*

1. Provincial Key Laboratory of Biotechnology of Shaanxi, Lab of Tissue Engineering, School of Life Science, Northwest University, 229 North TaiBai Road, Xi’an, Shaanxi Province 710069, P.R. China.

2. Key Laboratory of Resource Biology and Modern Biotechnology in Western China, Ministry of Education, Northwest University, 229 North TaiBai Road, Xi’an, Shaanxi Province 710069, P.R. China.

 

DOI: 10.1021/acsami.8b01547

 

研究背景

研发生物相容性好、可降解、具有骨诱导特性组织工程骨,对骨再生和缺损修复具有重要临床意义。骨形成蛋白-2bone morphogenetic protein-2BMP-2)是一种高效骨诱导因子,涂覆或负载BMP-2的人工植入物作为骨修复材料是目前研究的热点。但是临床应用面临两个关键问题。首先,选择BMP-2的最佳治疗剂量低剂量的治疗效果不佳,而高剂量则可能引起多种副作用,例如骨增生脊髓损伤后异位骨化形成囊状骨质空洞、危及生命的颈部肿胀等炎症反应。其次,控制BMP-2有效释放短时间内无控快速释放不仅不利于成骨和修复,而且对机体会产生不利影响

 

研究结果(研究方案见图1,从离体和在体两方面进行)

  1. 构建的PLA-PD-BMP复合材料可用作骨组织工程支架。3D打印构建的PLA多孔支架材料,呈乳白色,PLA-PDPLA-PD-BMP材料呈棕色PD,聚多巴胺,呈棕色)BMP-2抗体-抗原反应实验证实BMP-2分子接枝成功。三种支架材料的孔隙率,杨氏模量均无统计学差异,证明PD-BMP修饰并未破坏PLA的多孔微结构

  2. PLA-PD-BMP可负载低剂量BMP-21μg),并实现BMP-2的可控释放,同时检测到PLA-PD-BMP表面释放的BMP-2参与骨诱导;

  3. 载有低剂量BMP-21μg)的PLA-PD-BMP材料能促进MSC(骨髓间充质干细胞)粘附和增殖,并促进MSC向成骨细胞分化;

  4. 在体检测PLA-PD-BMP复合材料的成骨能力分别于2周和4周取出植入动物肌袋的材料,显微CT图像显示在PLA-PD-BMP组中形成了骨样组织PLA-PDPLA-BMP组中未见骨组织。HEMasson三色染色证实PLA-PD-BMP组的标本中新生骨组织,但PLA-PDPLA-BMP组标本中未见骨组织

 

研究结论

研究设计了一种BMP-2修饰PLA植入物的方法,并首次通过离体和在体实验充分验证了其有效性和安全性。采用此修饰方法制备的PLA-PD-BMP材料,BMP-2具有初期快速释放和后期缓慢释放的特点,释放速率可控保证了植入物在机体内的骨诱导和骨整合性能。同时,低剂量的BMP-2释放提高了临床使用的安全性。这种修饰方法有望成为将各种生长因子固定到不同基底材料上的通用方法。

 

日前,该成果The Influence of Mussel-Derived Bioactive BMP-2 Decorated PLA on MSCs Behavior in Vitro and Verification with Osteogenicity at Ectopic Sites in Vivo”已在美国化学会《ACS Applied Materials & Interfaces》杂志(2017年影响因子7.504)在线发表。生命科学学院师资博士后陈卓玥为论文第一作者,生命科学学院特聘百人教授商立军为论文通讯作者。


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Figure 1. PLA-PD-BMP coating and self-assembly processes, and in vivo and in vitro tests with ectopic bone model and MSCs. (a) Preparation of polydopamine coating, (b) preparation of self-assembly of PLA-PD-BMP, (c) The in vitro test of the PLA-PD-BMP with MSCs, and (d) The in vivo efficacy test of the PLA-PD-BMP on rat ectopic bone model


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Figure 2. SEM images of cell attachment on each scaffold. SEM images of MSCs attached on the surfaces of PLA, PLA-PD, and PLA-PD-BMP after cultured for 4 h, 6 h and 8 h, respectively. The MSCs adhering to the surface of PLA-PD-BMP exhibited pseudopodia and spreading after only 4h culture. However, a few MSCs spread on the surface of the PLA and PLA-PD until 8 hours culture.



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Figure 3. Morphological and quantitative examination of specimens in vivo. Micro-CT analysis of the effects of PLA-PD (a, 2 weeks; b, 4 weeks), PLA-PD-BMP (c, 2 weeks; d, 4 weeks) and PLA-BMP (e, 2 weeks; f, 4 weeks) on ectopic bone formation. There was no new bone formed in the PLA-PD group and the PLA-BMP group. (g) Bone volume fraction quantified from micro-CT scans of harvested implants. (*p < 0.05, **p < 0.01, mean ± SD, n=4). There are no significant differences between the PLA-PD-BMP-implanted 4 weeks and the normal SD rat calvarium (p > 0.05, n=4)

 
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