可调节甲基丙烯酸化去细胞心脏基质:用于心脏组织工程的多功能支架

Tunable methacrylated decellularized heart matrix: a versatile scaffold for cardiac tissue engineering.

作者信息

Pierre Valinteshley, Wu Douglas H, Liu Chao, Ertugral Elif, Kothapalli Chandrasekhar, Senyo Samuel E

机构信息

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.

Medical Scientist Training Program, Case Western Reserve University, Cleveland, OH, United States.

出版信息

Front Bioeng Biotechnol. 2025 Jun 12;13:1579246. doi: 10.3389/fbioe.2025.1579246. eCollection 2025.

Abstract

Therapeutic tissue regeneration remains a significant unmet need in heart failure and cardiovascular disease treatment, which are among the leading causes of death globally. Decellularized heart matrix (DHM) offer promising advantages for tissue engineering, including low immunogenicity and seamless integration into biological processes, facilitating biocompatibility. However, DHM is challenged by weak mechanical properties that limit its utility to biomedical applications like tissue engineering. To address this limitation, we functionalized DHM with methacryloyl functional groups (DHMMA) that support UV-induced crosslinking to enhance mechanical properties. By modulating the degree of methacryloyl substitution, a broad range of stiffness was achieved while maintaining cell viability on crosslinked DHMMA. Additionally, we show that increasing UV exposure time and pH increases DHMMA stiffness. Furthermore, topographical features transferred on DHMMA via soft lithography facilitated physical orientation of cells in culture. We demonstrate DHMMA as a scaffold with tunable stiffness and matrix-degradation properties suitable for cell survival and microfabrication for cardiac tissue engineering applications.

摘要

治疗性组织再生在心力衰竭和心血管疾病治疗中仍然是一个尚未得到满足的重大需求,而心力衰竭和心血管疾病是全球主要死因之一。去细胞心脏基质(DHM)在组织工程方面具有诸多优势,包括低免疫原性以及能无缝融入生物过程,有助于生物相容性。然而,DHM面临机械性能较弱的挑战,这限制了其在组织工程等生物医学应用中的效用。为解决这一限制,我们用支持紫外线诱导交联以增强机械性能的甲基丙烯酰官能团(DHMMA)对DHM进行功能化处理。通过调节甲基丙烯酰取代度,在保持交联DHMMA上细胞活力的同时实现了广泛的硬度范围。此外,我们表明增加紫外线照射时间和pH值会增加DHMMA的硬度。此外,通过软光刻技术转移到DHMMA上的拓扑特征促进了培养中细胞的物理定向。我们证明DHMMA是一种具有可调硬度和基质降解特性的支架,适用于心脏组织工程应用中的细胞存活和微制造。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ca2/12198208/7fceb61921ba/fbioe-13-1579246-g001.jpg

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