软骨细胞球负载微孔水凝胶生物3D打印软骨再生技术

IF 6.8 3区 医学 Q1 ENGINEERING, BIOMEDICAL
Ruiquan Liu, Litao Jia, Jianguo Chen, Y. Long, Jinshi Zeng, Siyu Liu, Bo Pan, Xia Liu, Haiyue Jiang
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引用次数: 0

摘要

三维生物打印技术为特定形状软骨的再生带来了新的前景。在软骨生物打印中,满载软骨细胞的水凝胶是最常用的生物墨水。然而,在传统的生物连接中,细胞的分散和水凝胶的致密结构可能会限制细胞-细胞/细胞-细胞外基质(ECM)的相互作用,不利于软骨的再生和成熟。为了解决这一问题,在本研究中,我们开发了一种基于软骨细胞球体(CSs)和微孔水凝胶的软骨生物打印功能生物链接,其中软骨细胞球体作为多细胞聚集体可以提供广泛的细胞-细胞/细胞- ecm相互作用来模拟天然软骨微环境,微孔水凝胶可以为软骨细胞的生长和融合提供空间和通道。首先,我们采用无黏着微孔系统高通量制备了均匀自组装的CSs,并评估了不同的CSs制备参数(细胞数量和培养时间)对CSs的影响,这有助于制备适合软骨生物打印的生物墨水。然后,将聚氧化物(PEO)引入到甲基丙烯酸明胶(GelMA)中制备微孔水凝胶。最后,打印负载cs的微孔水凝胶,并将其植入裸鼠体内。结果表明,500个细胞培养1 d的CSs在微孔水凝胶中的增殖和生长能力优于细胞数量较多、培养时间较长的CSs。此外,结果还表明,cs -负载生物链接可以成功打印成预定义的晶格形状结构,细胞损伤小,并在体内再生软骨组织,其结构与天然软骨相似,具有典型的腔隙结构和丰富的软骨特异性ECM沉积。综上所述,我们的研究验证了使用CSs作为软骨生物打印构建块的可行性和优势,为患者特异性形状软骨的制造和再生提供了新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chondrocyte spheroid-laden microporous hydrogel-based 3D bioprinting for cartilage regeneration
Three-dimensional (3D) bioprinting has brought new promising strategies for the regeneration of cartilage with specific shapes. In cartilage bioprinting, chondrocyte-laden hydrogels are the most commonly used bioinks. However, the dispersion of cells and the dense texture of the hydrogel in the conventional bioink may limit cell–cell/ cell–extracellular matrix (ECM) interactions, counting against cartilage regeneration and maturation. To address this issue, in this study, we developed a functional bioink for cartilage bioprinting based on chondrocyte spheroids (CSs) and microporous hydrogels, in which CSs as multicellular aggregates can provide extensive cell– cell/cell–ECM interactions to mimic the natural cartilage microenvironment, and microporous hydrogels can provide space and channel for the growth and fusion of the CSs. Firstly, we used a non-adhesive microporous system to produce homogeneous self-assembled CSs in high-throughput and evaluated the influence of different CSs preparation parameters (cell number and culture time) on CSs, which aids in the preparation of bioink suitable for cartilage bioprinting. Then, polyethylene oxide (PEO) was introduced into gelatin methacrylate (GelMA) to prepare microporous hydrogel. Finally, the CS-laden microporous hydrogels were printed, and the constructs were implanted into nude mice. The results showed that the CSs with 500 cells cultured for 1 day exhibited better proliferation and growth ability in microporous hydrogels compared to those with more cells and cultured for longer time. In addition, the results also demonstrated that the CS-laden bioink can be successfully printed into predefined lattice-shape constructs with little cell damage and regenerated cartilage tissue in vivo with a structure similar to natural cartilage characterized by typical lacunae structure and abundant cartilage-specific ECM deposition. In summary, our study verified the feasibility and advantages of using CSs as building blocks in cartilage bioprinting, which provides novel strategies for the fabrication and regeneration of patient-specific shaped cartilage.  
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来源期刊
CiteScore
6.90
自引率
4.80%
发文量
81
期刊介绍: The International Journal of Bioprinting is a globally recognized publication that focuses on the advancements, scientific discoveries, and practical implementations of Bioprinting. Bioprinting, in simple terms, involves the utilization of 3D printing technology and materials that contain living cells or biological components to fabricate tissues or other biotechnological products. Our journal encompasses interdisciplinary research that spans across technology, science, and clinical applications within the expansive realm of Bioprinting.
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