Du Kun, Wang Bei, Yang Ning, Jin Jian, Liu Wei, Pu Feifei, Zou Lili, Qu Zilu, Chen Liuqing
Hubei Province Key Laboratory of Skin Infection and Immunity, Wuhan No. 1 Hospital, Wuhan 430022, China.
Department of Medical Equipment, Wuhan No. 1 Hospital, Wuhan 430022, China.
ACS Omega. 2025 Jun 2;10(23):24284-24295. doi: 10.1021/acsomega.5c00222. eCollection 2025 Jun 17.
Drug-induced liver injury is the main cause of acute liver failure and has become a major health problem. Nowadays, topical and transdermal drug delivery has appeared as a popular approach to deliver drugs, and its risk of inducing hepatotoxicity requires careful evaluation before approval for application to humans. To date, hepatotoxicity resulting from topical administration has rarely been studied due to the lack of effective research models. Here, a highly biomimetic liver-skin microphysiological system (LS-MPS) was developed, providing a dynamic and physiologically similar microenvironment to mimic in vivo liver, skin, and cyclic flow between them. The three-dimensional (3D) liver microtissue and 3D skin microtissue were successfully established on the LS-MPS. The skin microtissue showed high cell viability and physiologically similar dermal and epidermal layers. More importantly, the barrier and permeability functions of skin were maintained for long-term culture. The 3D liver microtissue showed high cell viability, biomimetic cell arrangement, and active metabolic function. In addition, the LS-MPS was applied to evaluate the topical delivery of drug-induced liver injury, demonstrating its potential in drug safety testing. Thus, this study provides a promising platform to assess complex drug toxicity, which contributes to the development of new drugs.
药物性肝损伤是急性肝衰竭的主要原因，已成为一个重大的健康问题。如今，局部和透皮给药已成为一种流行的给药方式，其诱导肝毒性的风险在批准用于人体之前需要仔细评估。迄今为止，由于缺乏有效的研究模型，局部给药引起的肝毒性很少被研究。在此，开发了一种高度仿生的肝-皮肤微生理系统（LS-MPS），提供了一个动态且生理相似的微环境，以模拟体内肝脏、皮肤以及它们之间的循环流动。在LS-MPS上成功建立了三维（3D）肝脏微组织和3D皮肤微组织。皮肤微组织显示出高细胞活力以及生理相似的真皮和表皮层。更重要的是，皮肤的屏障和渗透功能在长期培养中得以维持。3D肝脏微组织显示出高细胞活力、仿生的细胞排列以及活跃的代谢功能。此外，LS-MPS被应用于评估药物性肝损伤的局部给药，证明了其在药物安全性测试中的潜力。因此，本研究提供了一个评估复杂药物毒性的有前景的平台，这有助于新药的开发。
