FXa-Responsive Hydrogels to Craft Corneal Endothelial Lamellae.

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Mikhail V Tsurkan, Juliane Bessert, Rabea Selzer, Sarah D Tsurkan, Dagmar Pette, Manfred F Maitz, Petra B Welzel, Carsten Werner
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引用次数: 0

Abstract

Cell-instructive polymer hydrogels are instrumental in tissue engineering for regenerative therapies. Implementing defined and selective responsiveness to external stimuli is a persisting challenge that critically restricts their functionality. Addressing this challenge, this study introduces a versatile, modular hydrogel system composed of four-arm poly(ethylene glycol)(starPEG)-peptide and glycosaminoglycan(GAG)-maleimide conjugates. The gel system features a small peptide sequence that is selectively cleaved by the coagulation factor FXa. In a cell culture environment, where active FXa is absent, the hydrogel remains stable, providing a conducive matrix for the growth of complex tissue structures or organoids. Upon the introduction of FXa, the hydrogel is designed to disintegrate rapidly, enabling the gentle release of the cultivated tissues without impairing their functionality. The efficacy of this approach is demonstrated through the ex vivo development, detachment, and transplantation of human corneal endothelial lamellae, achieving sizes relevant for clinical application in Descemet Membrane Endothelial Keratoplasty (DMEK). Furthermore, the practicality of the hydrogel system is validated in vitro using a de-endothelialized porcine cornea as a surrogate recipient. Since the FXa-cleavable peptide can be integrated into a variety of multifunctional hydrogels, it can pave the way for next-generation scaffold-free tissue engineering and organoid regenerative therapies.

fxa反应性水凝胶制备角膜内皮层。
指导细胞的聚合物水凝胶在再生治疗的组织工程中起着重要作用。实现对外部刺激的定义和选择性反应是一个持续的挑战,严重限制了它们的功能。为了解决这一挑战,本研究引入了一种由四臂聚乙二醇(starPEG)-肽和糖胺聚糖(GAG)-马来酰亚胺偶联物组成的多功能模块化水凝胶体系。凝胶系统的特点是一个小的肽序列,被凝血因子FXa选择性地切割。在缺乏活性FXa的细胞培养环境中,水凝胶保持稳定,为复杂组织结构或类器官的生长提供了有利的基质。在引入FXa后,水凝胶被设计成快速分解,使培养组织能够在不损害其功能的情况下缓慢释放。这种方法的有效性通过离体发育、剥离和移植的人角膜内皮层来证明,达到了与Descemet膜内皮角膜移植术(DMEK)临床应用相关的尺寸。此外,使用去内皮化的猪角膜作为替代受体,在体外验证了水凝胶系统的实用性。由于fxa可切割肽可以整合到各种多功能水凝胶中,它可以为下一代无支架组织工程和类器官再生治疗铺平道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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