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用于骨组织工程的、用脱细胞骨细胞外基质功能化的聚癸二酸甘油酯支架的生物制造。

Biofabrication of Poly(glycerol sebacate) Scaffolds Functionalized with a Decellularized Bone Extracellular Matrix for Bone Tissue Engineering.

作者信息

Guler Selcan, Eichholz Kian, Chariyev-Prinz Farhad, Pitacco Pierluca, Aydin Halil Murat, Kelly Daniel J, Vargel İbrahim

机构信息

Bioengineering Division, Institute of Science and Engineering, Hacettepe University, 06800 Ankara, Turkey.

Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02 R590 Dublin, Ireland.

出版信息

Bioengineering (Basel). 2022 Dec 25;10(1):30. doi: 10.3390/bioengineering10010030.

Abstract

The microarchitecture of bone tissue engineering (BTE) scaffolds has been shown to have a direct effect on the osteogenesis of mesenchymal stem cells (MSCs) and bone tissue regeneration. Poly(glycerol sebacate) (PGS) is a promising polymer that can be tailored to have specific mechanical properties, as well as be used to create microenvironments that are relevant in the context of BTE applications. In this study, we utilized PGS elastomer for the fabrication of a biocompatible and bioactive scaffold for BTE, with tissue-specific cues and a suitable microstructure for the osteogenic lineage commitment of MSCs. In order to achieve this, the PGS was functionalized with a decellularized bone (deB) extracellular matrix (ECM) (14% and 28% by weight) to enhance its osteoinductive potential. Two different pore sizes were fabricated (small: 100-150 μm and large: 250-355 μm) to determine a preferred pore size for in vitro osteogenesis. The decellularized bone ECM functionalization of the PGS not only improved initial cell attachment and osteogenesis but also enhanced the mechanical strength of the scaffold by up to 165 kPa. Furthermore, the constructs were also successfully tailored with an enhanced degradation rate/pH change and wettability. The highest bone-inserted small-pore scaffold had a 12% endpoint weight loss, and the pH was measured at around 7.14. The in vitro osteogenic differentiation of the MSCs in the PGS-deB blends revealed a better lineage commitment of the small-pore-sized and 28% (/) bone-inserted scaffolds, as evidenced by calcium quantification, ALP expression, and alizarin red staining. This study demonstrates a suitable pore size and amount of decellularized bone ECM for osteoinduction via precisely tailored PGS elastomer BTE scaffolds.

摘要

骨组织工程(BTE)支架的微观结构已被证明对间充质干细胞(MSCs)的成骨作用和骨组织再生有直接影响。聚癸二酸甘油酯(PGS)是一种很有前景的聚合物,它可以被定制以具有特定的机械性能,还可用于创建与BTE应用相关的微环境。在本研究中,我们利用PGS弹性体制备了一种用于BTE的生物相容性和生物活性支架,该支架具有组织特异性线索以及适合MSCs成骨谱系定向分化的微观结构。为了实现这一目标,用脱细胞骨(deB)细胞外基质(ECM)(重量百分比为14%和28%)对PGS进行功能化处理,以增强其骨诱导潜力。制备了两种不同孔径(小:100 - 150μm和大:250 - 355μm)的支架,以确定体外成骨的最佳孔径。PGS的脱细胞骨ECM功能化不仅改善了细胞的初始附着和成骨作用,还将支架的机械强度提高了多达165 kPa。此外,构建体还成功地实现了降解速率/pH变化和润湿性的增强。含骨量最高的小孔径支架在终点时重量损失了12%,pH值测量约为7.14。PGS - deB混合物中MSCs的体外成骨分化表明,小孔径且含28%(/)骨的支架具有更好的谱系定向分化,这通过钙定量、碱性磷酸酶(ALP)表达和茜素红染色得到了证实。本研究通过精确定制的PGS弹性体BTE支架,证明了用于骨诱导的合适孔径和脱细胞骨ECM的量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ba2/9854839/fc85db7f7aaa/bioengineering-10-00030-g001.jpg

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