Yau Anne, Sands Ian, Zhang Wuxia, Chen Yupeng
Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.
bioRxiv. 2024 Oct 10:2024.10.05.616785. doi: 10.1101/2024.10.05.616785.
Engineered cartilage tissues have wide applications in in vivo cartilage repair as well as in vitro models, such as cartilage-on-a-chip or cartilage tissue chips. Currently, most cartilage tissue engineering approaches focus on promoting chondrogenesis of stem cells to produce regenerated cartilage. However, this regenerated cartilage can dedifferentiate into fibrotic tissue or further differentiate into hypertrophic or calcified cartilage. One of the most challenging objectives in cartilage tissue engineering is to maintain long-term cartilage homeostasis. Since the microenvironment of engineered cartilage tissue is crucial for stem cell adhesion, proliferation, differentiation, and function, we aim to develop a novel scaffold that can maintain the long-term homeostasis of regenerated cartilage. Therefore, we developed a library of Janus base nanomatrices (JBNms), composed of DNA-inspired Janus nanotubes (JBNts) as well as cartilage extracellular matrix (ECM) proteins. The JBNms were developed to selectively promote chondro-lineage cell functions while inhibiting bone and endothelial cell growth. More importantly, the JBNm can effectively promote chondrogenesis while inhibiting hypertrophy, osteogenesis, angiogenesis, and dedifferentiation. Additionally, the JBNm is injectable, forming a solid scaffold suitable for producing and maintaining regenerated cartilage tissue in microfluidic chips, making it ideal for tissue chip applications. In this study, we successfully created cartilage tissue chips using JBNms. These chips can model cartilage tissue even after long-term culture and can also mimic arthritis progression, making them useful for drug screening. Thus, we have developed a novel nanomaterial approach for improved cartilage tissue engineering and cartilage tissue chip applications.
工程化软骨组织在体内软骨修复以及体外模型（如芯片上软骨或软骨组织芯片）中具有广泛应用。目前，大多数软骨组织工程方法专注于促进干细胞的软骨生成以产生再生软骨。然而，这种再生软骨可能会去分化为纤维化组织，或进一步分化为肥大或钙化软骨。软骨组织工程中最具挑战性的目标之一是维持长期的软骨内环境稳定。由于工程化软骨组织的微环境对于干细胞的黏附、增殖、分化和功能至关重要，我们旨在开发一种能够维持再生软骨长期内环境稳定的新型支架。因此，我们开发了一个由受DNA启发的Janus纳米管（JBNts）以及软骨细胞外基质（ECM）蛋白组成的Janus碱基纳米基质（JBNms）库。开发JBNms的目的是选择性地促进软骨谱系细胞功能，同时抑制骨细胞和内皮细胞生长。更重要的是，JBNm可以有效促进软骨生成，同时抑制肥大、成骨、血管生成和去分化。此外，JBNm是可注射的，能形成一种适合在微流控芯片中产生和维持再生软骨组织的固体支架，使其成为组织芯片应用的理想选择。在本研究中，我们成功地使用JBNms创建了软骨组织芯片。即使经过长期培养，这些芯片仍能模拟软骨组织，还能模拟关节炎进展，使其可用于药物筛选。因此，我们开发了一种新型纳米材料方法，用于改进软骨组织工程和软骨组织芯片应用。
