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基于多组分原位可点击弹性蛋白样重组体系统的随机定向电纺纤维用于皮肤组织工程。

Random and oriented electrospun fibers based on a multicomponent, in situ clickable elastin-like recombinamer system for dermal tissue engineering.

机构信息

G.I.R BIOFORGE, CIBER-BBN, Edificio Lucia, Universidad de Valladolid, Paseo Belén 19, 47011 Valladolid, Spain.

出版信息

Acta Biomater. 2018 May;72:137-149. doi: 10.1016/j.actbio.2018.03.027. Epub 2018 Mar 21.

Abstract

UNLABELLED

Herein we present a system to obtain fibers from clickable elastin-like recombinamers (ELRs) that crosslink in situ during the electrospinning process itself, with no need for any further treatment to stabilize them. These ELR-click fibers are completely stable under in vitro conditions. A wrinkled fiber morphology is obtained. In addition to a random fiber orientation, oriented fibers with a high degree of alignment and coherence can also be obtained by using a rotational electrode. The production of multicomponent fibers means that different functionalities, such as cell-adhesion domains (RGD peptides), can be incorporated into them. In a subsequent study, two main cell lines present in the dermis and epidermis, namely keratinocytes and fibroblasts, were cultured on top of the ELR-click fibers. Adhesion, proliferation, fluorescence, immunostaining and histology studies showed the cytocompatibility of these scaffolds, thus suggesting their possible use for wound dressings in skin tissue engineering applications.

STATEMENT OF SIGNIFICANCE

For the first time stable electrospun bioactive fibers are obtained by the in situ mixing of two "clickable" ELR components previously described by Gonzalez et al (Acta Biomaterialia 2014). This work describes an efficient system to prepare fibrous scaffolds based on peptidic polymers by electrospinning without the need of crosslinking agents that could be harmful for cells or living tissues. These bioactive fibers support cell growth due to the inclusion of RGD motifs (Staubli et al. Biomaterials 2017). Finally, the in vitro biocompatibility of the two main cell types found in the outer layers of skin, fibroblasts and keratinocytes, indicates that this system is of great interest to prepare elastic artificial skin substitutes for wound healing applications.

摘要

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本文提出了一种从可点击弹性蛋白样重组体(ELR)中获得纤维的系统,该系统在电纺过程中原位交联,无需任何进一步的处理来稳定它们。这些 ELR 点击纤维在体外条件下完全稳定。可以获得皱缩的纤维形态。除了随机的纤维取向外,通过使用旋转电极还可以获得具有高度取向和连贯性的取向纤维。多组分纤维的生产意味着不同的功能,如细胞粘附域(RGD 肽),可以被纳入其中。在随后的研究中,两种主要存在于真皮和表皮中的细胞系,即角质形成细胞和成纤维细胞,被培养在 ELR 点击纤维的顶部。粘附、增殖、荧光、免疫染色和组织学研究表明这些支架具有细胞相容性,因此表明它们可能用于皮肤组织工程应用中的伤口敷料。

意义声明

首次通过混合 Gonzalez 等人之前描述的两种“可点击”ELR 成分(Acta Biomaterialia 2014)原位获得稳定的电纺生物活性纤维。这项工作描述了一种通过电纺制备基于肽聚合物的纤维支架的有效系统,无需使用可能对细胞或活组织有害的交联剂。由于包含 RGD 基序(Staubli 等人,Biomaterials 2017),这些生物活性纤维支持细胞生长。最后,在皮肤外层发现的两种主要细胞类型(成纤维细胞和角质形成细胞)的体外生物相容性表明,该系统对于制备弹性人工皮肤替代品用于伤口愈合应用具有重要意义。

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