Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering.

Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering.
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用于骨软骨组织工程的含有透明质酸和 Sr/Zn 叶酸的仿生梯度支架。

DOI:
10.3390/polym14010012
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发表时间:
2021-12-21
期刊:
影响因子:
5
通讯作者:
Rojo L
Rojo L
中科院分区:
工程技术3区
文献类型:
--
作者:
Asensio G;Benito-Garzón L;Ramírez-Jiménez RA;Guadilla Y;Gonzalez-Rubio J;Abradelo C;Parra J;Martín-López MR;Aguilar MR;Vázquez-Lasa B;Rojo L

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基于组织工程的再生疗法正在成为治疗骨关节炎和类风湿性关节炎的最有前途的替代方案。然而,再生的全层关节骨软骨缺损,再现天然软骨和骨软骨界面的复杂性仍然是具有挑战性的。因此,在这项工作中,我们提出了制造,物理化学表征,并在体外和体内评价仿生层次支架,模仿的空间组织和组成的软骨和骨软骨界面。该支架由聚(乙二醇)二甲基丙烯酸酯(PEGDMA)在可生物降解的聚(D,L-丙交酯-共-乙交酯)(PLGA)、生物活性磷酸三钙β-TCP和促骨叶酸锶(SrFO)存在下低温聚合而成的复合多孔支撑物,以及含有生物活性锌叶酸衍生物(ZnFO)的梯度仿生光聚合甲基丙烯酸酯化透明质酸(HAMA)基水凝胶组成。分级支架的显微镜分析显示开放互连多孔开放的微观结构,体外行为结果表明具有持续降解速率的高溶胀能力。3周的体外释放研究表明生物活性化合物的持续浸出,即,Sr 2+、Zn 2+和叶酸,在生物活性范围内,对人成骨细胞(hOB)和人关节软骨细胞(hAC)培养物没有负面影响。hOB和hAC的体外共培养揭示了根据基质微观结构和组成的引导细胞定殖和增殖。在体内兔髁突实验中,在一个临界尺寸的缺损模型显示的仿生支架,以促进软骨样组织的再生的支架和骨软骨组织的新生的能力。
Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr2+, Zn2+ and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.
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