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Published January 1, 2026 | Version v1
Journal article Open

Engineering biomimetic tissue barrier models on chips: From design and fabrication to applications in disease modeling and drug screening

Creators

  • 1. Tecnol Monterrey, Sch Engn & Sci, Ave Eugenio Garza Sada 2501, Monterrey 64849, NL, Mexico
  • 2. Ege Univ, Grad Sch Nat & Appl Sci, Dept Bioengn, Bornova, Turkiye
  • 3. Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA
  • 4. Terasaki Inst Biomed Innovat, Los Angeles, CA 90064 USA
  • 5. Univ Bonn, Med Fac, Dept Ophthalmol, Bonn, Germany
  • 6. Stanford Univ, Dept Radiat Oncol, Div Med Phys, Stanford, CA USA

Description

Replicating the in vitro properties of tissue barriers-such as the blood-brain barrier, gut, skin, lung, kidney, retina, nasal epithelium, and placenta-is crucial for many applications, including drug screening, studying molecular transport, drug delivery, and disease modeling in preclinical studies. Organ-on-a-chip (OoC) platforms are advanced three-dimensional (3D) in vitro models that aim to replicate various aspects of organ functionality within microfluidic systems by providing microenvironments akin to native tissue. When used to model the interface between two different tissue compartments, OoC technology offers a promising platform for more accurately replicating the physiology and pathophysiology of various tissue barriers in the body. This review focuses on the state-of-the-art biomimetic tissue barrier models, ranging from two-channel tissue barrier-on-achip systems with a thin porous membrane to hydrogel-based membrane models. Specifically, it explores the engineering of tissue barrier-on-a-chip platforms, highlighting various fabrication techniques for microfluidic chips and membranes, as well as methods for functional characterization of the engineered tissue barriers. Additionally, we discuss the development of organ-specific barrier models and multi-organ-on-a-chip systems for studying inter-organ communication. Finally, we highlight the current challenges in the field and future di-rections in advancing tissue barrier modeling using OoC technology.

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