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胶原蛋白介导的原位矿化增强仿生骨组织工程支架

Collagen-mediated in situ mineralization-enhanced biomimetic bone tissue engineering scaffolds.

作者信息

Shi Rui, Wang Xiaotong, Gang Fangli, Shi Jiayu, Wang Shuping, Liu Wanting, Ye Weilong, Sun Xiaodan

机构信息

Department of Biology, Xinzhou Normal University, Xinzhou 034000, China.

Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Department of Orthognathic Surgery, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin 300041, China.

出版信息

Colloids Surf B Biointerfaces. 2025 Jun;250:114566. doi: 10.1016/j.colsurfb.2025.114566. Epub 2025 Feb 17.

DOI:10.1016/j.colsurfb.2025.114566
PMID:39965482
Abstract

Oriented poly(lactic acid) (PLA) fiber bone tissue engineering scaffolds are often limited by factors including poor material hydrophilicity and weak osteogenic activity. The introduction of in situ mineralization can address these issues, but it requires the assistance of hydrophilic materials to achieve optimal performance. Collagen, a nature-based ECM component, was adopted because it can enhance hydrophilicity, encourage cell adhesion, and biomimetrically induce mineralization, according to recent studies of ECM-mimicking scaffolds. Therefore, this study proposes a collagen-mediated in situ mineralization-enhanced scaffold design aimed at improving the hydrophilicity and osteogenic potential of oriented fiber scaffolds. Collagen (5-10 wt%) and phosphate-containing solutions (59.6 mM) were added to a PLA matrix, and scaffolds were electrospun at 12 kV. Subsequently, the scaffolds underwent in situ mineralization in a calcium ion-containing solution (101 mM), leading to the formation of calcium phosphate within the scaffold structure. The experimental results show that the introduction of collagen effectively promoted the formation of in situ mineralization, enhanced the hydrophilicity of the scaffold, and maintained good fiber orientation. The scaffolds exhibited significant mechanical anisotropy, with the Young's modulus parallel to the fiber direction reaching 5 MPa, which is 25 times greater than that in the direction perpendicular to the fibers. In vitro studies with rat bone marrow mesenchymal stem cells showed a 2.4-fold increase in osteogenic differentiation, as assessed by alkaline phosphatase activity. Micro-CT analysis showed that the increase of BV/TV was 3.26 times higher when compared to that of control scaffolds, while histological analysis revealed mature bone tissue formation characterized by well-organized collagen fibers. Overall, the present study describes a novel strategy of collagen-mediated in situ mineralization, first integrating enhanced hydrophilicity, mechanical anisotropy, and biomimetic bone-like properties to address major limitations associated with the current oriented fiber scaffolds.

摘要

取向聚乳酸(PLA)纤维骨组织工程支架通常受到包括材料亲水性差和成骨活性弱等因素的限制。引入原位矿化可以解决这些问题,但需要亲水性材料的辅助才能实现最佳性能。胶原蛋白是一种基于天然的细胞外基质(ECM)成分,根据最近对模拟ECM支架的研究,因其能够增强亲水性、促进细胞黏附并仿生诱导矿化而被采用。因此,本研究提出了一种胶原蛋白介导的原位矿化增强支架设计,旨在提高取向纤维支架的亲水性和成骨潜力。将胶原蛋白(5 - 10 wt%)和含磷酸盐溶液(59.6 mM)添加到PLA基质中,并在12 kV下进行静电纺丝制备支架。随后,支架在含钙离子溶液(101 mM)中进行原位矿化,导致在支架结构内形成磷酸钙。实验结果表明,胶原蛋白的引入有效地促进了原位矿化的形成,增强了支架的亲水性,并保持了良好的纤维取向。支架表现出显著的力学各向异性,平行于纤维方向的杨氏模量达到5 MPa,是垂直于纤维方向的25倍。对大鼠骨髓间充质干细胞的体外研究表明,通过碱性磷酸酶活性评估,成骨分化增加了2.4倍。显微CT分析表明,与对照支架相比,骨体积分数(BV/TV)的增加高出3.26倍,而组织学分析显示形成了以组织良好的胶原纤维为特征的成熟骨组织。总体而言,本研究描述了一种胶原蛋白介导的原位矿化新策略,首次整合了增强的亲水性、力学各向异性和仿生骨样特性,以解决与当前取向纤维支架相关的主要局限性。

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