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使用肾脏特异性细胞外基质生物墨水系统进行3D生物打印肾脏构建体以促进肾脏再生

3D Bioprinted Renal Constructs Using Kidney-Specific ECM Bioink System on Kidney Regeneration.

作者信息

Carreno-Caleano Gabriel, Ali Mohamed, Yoo James J, Lee Sang Jin, Atala Anthony

机构信息

Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.

Department of Biochemistry, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt.

出版信息

Adv Healthc Mater. 2025 Jun 26:e2502576. doi: 10.1002/adhm.202502576.

Abstract

The final stage of chronic kidney disease (CKD) remains an irreversible condition, with dialysis and transplantation as the only treatment options. Recently, 3D bioprinting has emerged as a promising strategy for bioengineering renal constructs capable of restoring damaged kidney. A critical challenge in this approach is the development of a kidney-specific bioink that provides an optimal biochemical and biomechanical microenvironment to support renal cell organization, maturation, and functional restoration. In this study, a kidney-derived decellularized extracellular matrix bioink (kdECMMA) to facilitate renal tissue bioprinting is utilized. The kdECMMA bioink exhibits excellent printability, structural integrity, and biological characteristics. Human kidney cells encapsulated within the bioprinted kdECMMA constructs demonstrate high viability and progressive maturation over time. To evaluate its in vivo feasibility, bioprinted renal constructs into the kidneys of nude rats are implanted. After 1 and 2 months, the implanted constructs display newly formed glomerular- and tubular-like structures, with human-specific markers confirming the integration of human cells within these formations. Particularly, renal tissue formation is also observed in cell-free kdECMMA constructs, suggesting the recruitment of host renal progenitor cells into the implantation site. These findings highlight the potential of kdECMMA bioinks in creating a kidney-specific microenvironment conducive to renal regeneration.

摘要

慢性肾脏病(CKD)的终末期仍然是一种不可逆的病症,透析和移植是仅有的治疗选择。最近,3D生物打印已成为一种有前景的策略,用于生物工程构建能够修复受损肾脏的肾组织。这种方法中的一个关键挑战是开发一种肾脏特异性生物墨水,它能提供一个最佳的生化和生物力学微环境,以支持肾细胞的组织、成熟和功能恢复。在本研究中,使用了一种源自肾脏的脱细胞细胞外基质生物墨水(kdECMMA)来促进肾组织生物打印。kdECMMA生物墨水表现出优异的可打印性、结构完整性和生物学特性。封装在生物打印的kdECMMA构建体中的人肾细胞随着时间的推移显示出高活力和逐渐成熟。为了评估其体内可行性,将生物打印的肾组织构建体植入裸鼠的肾脏中。1个月和2个月后,植入的构建体显示出新形成的肾小球样和肾小管样结构,人类特异性标记物证实了人类细胞在这些结构中的整合。特别地,在无细胞的kdECMMA构建体中也观察到肾组织形成,这表明宿主肾祖细胞被招募到植入部位。这些发现突出了kdECMMA生物墨水在创建有利于肾再生的肾脏特异性微环境方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5914/12447042/0dbb481fb87b/ADHM-14-0-g004.jpg

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