Development and evaluation of a microfluidic human testicular tissue chip: a novel <i>in vitro</i> platform for reproductive biology and pharmacology studies.

Abstract

Organ-on-a-chip culture systems using human organ tissues provide invaluable preclinical insights into systemic functions <i>in vitro</i>. This study aimed to develop a novel human testicular tissue chip within a microfluidic device employing computer-aided design software and photolithography technology. Polydimethylsiloxane was used as the primary material to ensure marked gas permeability and no biotoxicity, enabling effective mimicry of the <i>in vivo</i> testicular microenvironment. This biochip preserved the structural integrity and cellular composition of human testicular tissue, as well as part of its functionality, over an extended period <i>in vitro</i>. Moreover, compared to traditional static culture methods, it more effectively maintained tissue viability and endocrine function. The chip maintained cellular components, histological morphology, and an ultrastructure similar to those <i>in vivo</i>. Notably, the addition of gonadotropins to the human testis tissue on the chip resulted in consistent and steady <i>in vitro</i> production of testosterone and inhibin B. Additionally, the chip displayed sensitivity to the reproductive toxicity of the chemotherapeutic drug busulfan. The results demonstrate the successful establishment of a novel human testicular tissue chip culture system, providing a novel <i>in vitro</i> approach enabling the exploration of human reproductive biology, reproductive pharmacology, toxicology, individual diagnosis, and treatment strategies.