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载有褪黑素/替度鲁肽的核/壳 PMMA/丝素静电纺纤维的可注射甲基丙烯酰化明胶/巯基化果胶水凝胶用于活髓再生。

Injectable methacrylated gelatin/thiolated pectin hydrogels carrying melatonin/tideglusib-loaded core/shell PMMA/silk fibroin electrospun fibers for vital pulp regeneration.

机构信息

Department of Engineering Sciences, Middle East Technical University, Ankara 06800, Turkey; MODSIMMER, Modeling and Simulation Research & Development Center, Middle East Technical University, Ankara 06800, Turkey; BIOMATEN, CoE in Biomaterials & Tissue Engineering, Middle East Technical University, Ankara 06800, Turkey; Institute of Biomedical Engineering & Nanomedicine (IBEN), National Health Research Institutes, Miaoli 35053, Taiwan.

Department of Engineering Sciences, Middle East Technical University, Ankara 06800, Turkey; MODSIMMER, Modeling and Simulation Research & Development Center, Middle East Technical University, Ankara 06800, Turkey; BIOMATEN, CoE in Biomaterials & Tissue Engineering, Middle East Technical University, Ankara 06800, Turkey.

出版信息

Colloids Surf B Biointerfaces. 2023 Feb;222:113078. doi: 10.1016/j.colsurfb.2022.113078. Epub 2022 Dec 12.

DOI:10.1016/j.colsurfb.2022.113078
PMID:36525752
Abstract

Use of injectable hydrogels attract attention in the regeneration of dental pulp due to their ability to fill non-uniform voids such as pulp cavities. Here, gelatin methacrylate/thiolated pectin hydrogels (GelMA/PecTH) carrying electrospun core/shell fibers of melatonin (Mel)-polymethylmethacrylate (PMMA)/Tideglusib (Td)-silk fibroin (SF) were designed as an injectable hydrogel for vital pulp regeneration, through prolonged release of Td and Mel to induce proliferation and odontoblastic differentiation of dental pulp stem cells (DPSC). H NMR and FTIR confirmed methacrylation of Gel and thiolation of Pec. Addition of PMMA/SF increased degradation and water retention capacities of GelMA/PecTH. Rheological analyses and syringe tests proved the injectability of the hydrogel systems. Release studies indicated that Td and Mel were released from the fibers inside the hydrogels sequentially due to their specific locations. This release pattern from the hydrogels resulted in DPSC proliferation and odontogenic differentiation in vitro. Gene expression studies showed that the upregulation of DMP1, DSPP, and Axin-2 genes was promoted by GelMA/PecTH carrying PMMA/SF loaded with Mel (50 µg/mL) and Td (200 nM), respectively. Our results suggest that this hydrogel system holds promise for use in the regeneration of pulp tissue.

摘要

由于可注射水凝胶能够填充牙髓腔等非均匀空隙,因此在牙髓再生中受到关注。在这里,我们设计了一种载有褪黑素(Mel)-聚甲基丙烯酸甲酯(PMMA)/替度鲁肽(Td)-丝素纤维(SF)电纺核/壳纤维的明胶甲基丙烯酰基/巯基化果胶水凝胶(GelMA/PecTH),作为一种可注射水凝胶,用于牙髓的活力再生,通过持续释放 Td 和 Mel 来诱导牙髓干细胞(DPSC)的增殖和牙本质分化。1H NMR 和 FTIR 证实了 Gel 的甲基丙烯酰化和 Pec 的巯基化。PMMA/SF 的加入增加了 GelMA/PecTH 的降解和保水能力。流变学分析和注射器测试证明了水凝胶体系的可注射性。释放研究表明,由于特定位置,Td 和 Mel 从水凝胶内的纤维中依次释放。这种水凝胶的释放模式导致 DPSC 在体外增殖和牙源性分化。基因表达研究表明,GelMA/PecTH 携带载有 Mel(50μg/mL)和 Td(200nM)的 PMMA/SF 可促进 DMP1、DSPP 和 Axin-2 基因的上调。我们的结果表明,这种水凝胶系统有望用于牙髓组织的再生。

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