Development of an alginate-chitosan biopolymer composite with dECM bioink additive for organ-on-a-chip articular cartilage

开发用于器官芯片关节软骨的藻酸盐-壳聚糖生物聚合物复合材料与 dECM 生物墨水添加剂

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作者:Upasna Upadhyay, Saketh Kolla, Siddhartha Maredupaka, Swapna Priya, Kamma Srinivasulu, Lakshmi Kiran Chelluri

Abstract

In vitro use of articular cartilage on an organ-on-a-chip (OOAC) via microfluidics is challenging owing to the dense extracellular matrix (ECM) composed of numerous protein moieties and few chondrocytes, which has limited proliferation potential and microscale translation. Hence, this study proposes a novel approach for using a combination of biopolymers and decellularised ECM (dECM) as a bioink additive in the development of scalable OOAC using a microfluidic platform. The bioink was tested with native chondrocytes and mesenchymal stem cell-induced chondrocytes using biopolymers of alginate and chitosan composite hydrogels. Two-dimensional (2D) and three-dimensional (3D) biomimetic tissue construction approaches have been used to characterise the morphology and cellular marker expression (by histology and confocal laser scanning microscopy), viability (cell viability dye using flow cytometry), and genotypic expression of ECM-specific markers (by quantitative PCR). The results demonstrated that the bioink had a significant impact on the increase in phenotypic and genotypic expression, with a statistical significance level of p < 0.05 according to Student's t-test. The use of a cell-laden biopolymer as a bioink optimised the niche conditions for obtaining hyaline-type cartilage under culture conditions, paving the way for testing mechano-responsive properties and translating these findings to a cartilage-on-a-chip microfluidics system.

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