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3D 打印聚己内酯和牙髓干细胞负载 GelMA 的混合骨构建体。

3D printed hybrid bone constructs of PCL and dental pulp stem cells loaded GelMA.

机构信息

BIOMATEN Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University (METU), Ankara, Turkey.

Department of Biotechnology, Middle East Technical University (METU), Ankara, Turkey.

出版信息

J Biomed Mater Res A. 2021 Dec;109(12):2425-2437. doi: 10.1002/jbm.a.37235. Epub 2021 May 25.

Abstract

Fabrication of scaffolds using polymers and then cell seeding is a routine protocol of tissue engineering applications. Synthetic polymers have adequate mechanical properties to substitute for some bone tissue, but they are generally hydrophobic and have no specific cell recognition sites, which leads to poor cell affinity and adhesion. Some natural polymers, have high cell affinity but are mechanically weak and do not have the strength required as a bone supporting material. In the present study, 3D printed hybrid scaffolds were fabricated using PCL and GelMA carrying dental pulp stem cells (DPSCs), which is printed in the gaps between the PCL struts. This cell loaded GelMA was shown to support osteoinductivity, while the PCL provided mechanical strength needed to mimic the bone tissue. 3D printed PCL/GelMA and GelMA scaffolds were highly stable during 21 days of incubation in PBS. The compressive moduli of the hybrid scaffolds were in the range of the compressive moduli of trabecular bone. DPSCs were homogeneously distributed throughout the entire hydrogel component and exhibited high cell viability in both scaffolds during 21 days of incubation. Upon osteogenic differentiation DPSCs expressed two key matrix proteins, osteopontin and osteocalcin. Alizarin red staining showed mineralized nodules, which demonstrates osteogenic differentiation of DPSCs within GelMA. This construct yielded a very high cell viability, osteogenic differentiation and mineralization comparable to cell culture without compromising mechanical strength suitable for bone tissue engineering applications. Thus, 3D printed, cell loaded PCL/GelMA hybrid scaffolds have a great potential for use in bone tissue engineering applications.

摘要

使用聚合物制造支架,然后接种细胞,这是组织工程应用的常规方案。合成聚合物具有足够的机械性能来替代一些骨组织,但它们通常是疏水性的,没有特定的细胞识别位点,这导致细胞亲和力和黏附性差。一些天然聚合物具有较高的细胞亲和力,但机械强度较弱,不具备作为骨支持材料所需的强度。在本研究中,使用载有人牙髓干细胞(DPSCs)的 PCL 和 GelMA 制造了 3D 打印混合支架,这些细胞被打印在 PCL 支柱之间的间隙中。结果表明,负载细胞的 GelMA 支持成骨诱导性,而 PCL 则提供了模拟骨组织所需的机械强度。在 PBS 中孵育 21 天期间,3D 打印的 PCL/GelMA 和 GelMA 支架高度稳定。混合支架的压缩模量在小梁骨压缩模量范围内。DPSCs 均匀分布在整个水凝胶成分中,在孵育 21 天时两种支架中均表现出高细胞活力。在成骨分化后,DPSCs 表达了两种关键的基质蛋白,骨桥蛋白和骨钙素。茜素红染色显示矿化结节,表明 GelMA 内 DPSCs 的成骨分化。该构建体具有非常高的细胞活力、成骨分化和矿化能力,与不损害适合骨组织工程应用的机械强度的细胞培养相当。因此,3D 打印、细胞负载的 PCL/GelMA 混合支架在骨组织工程应用中具有很大的潜力。

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