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Material-centric design of organ-on-a-chip systems: Towards industrial translation and mass manufacturing
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DOI：10.1016/j.addr.2026.115945.png)
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Abstract
En 中文
Organs-on-chips (OoCs) are miniaturized devices for culturing and stimulating living cells within microscopic fluidic environments to create minimal organ surrogates. For the last decade, a diverse range of organ models were reconstructed at the micron scale to support the investigation of fundamental biological processes. By more accurately replicating the pathophysiology of human health, OoCs can serve as alternatives to conventional 2D cell culture and animal models for drug testing. However, moving from a research prototype to a commercially viable model system requires consideration of materials and manufacturing methods to simultaneously sustain high biological fidelity of organ mimicries, while enabling fabrication at scale. This review synthesizes recent advancements in that regard: We provide an overview of materials exhibiting relevant functional properties, their associated manufacturing methods, considerations of metrology and biocompatibility, and showcase representative examples of disruptive OoCs technologies currently integrated in the drug development pipeline to accelerate the discovery of safer and more effective therapeutics.
Keywords:
Organ-on-chip
In vitro models
Microfluidics
Polymers
Biomaterials
Manufacturing processes
Drug Discovery
APTES
(3-Aminopropyl)triethoxysilane
ADME
Absorption, distribution, metabolism, and excretion
ABS
Acrylonitrile butadiene styrene
ASA
Acrylonitrile styrene acrylate
AM
Additive manufacturing
ALI
Air–liquid interface
ALS
Amynotrophic lateral sclerosis
AI
Artificial intelligence
AFM
Atomic force microscopy
BBB
Blood–brain barrier
CAR
Chimeric antigen receptor
CNC
Computer numerical control
CAD
Computer-aided design
CD
Critical dimension
COP/COC
Cyclic olefin polymers/copolymers
DIC
Differential interference contrast
DLP
Digital light processing
EMA
European Medicines Agency
ECM
Extracellular matrix
FDA
U.S. Food & Drug Administration
FTIR
Fourier transform infrared
FDM
Fused deposition modeling
GelMA
Gelatin methacryloyl
iPSC
Human-induced pluripotent stem cell
IM
Injection molding
CMOS
Integrated complementary metal oxide semiconductor
IEC
International Electrotechnical Commission
ISO
International Organization for Standardization
LC–MS
Liquid chromatography-coupled mass spectrometry
LCD
Liquid crystal display
MEMS
Microelectromechanical systems
μCT
Microfocus X-ray computed tomography
MPS
Microphysiological systems
MOC
Multi-organ-on-a-chip
NAMs
New Approach Methodologies
OCT
Optical coherence tomography
OoC
Organ-on-a-chip
PFPE
Perfluoropolyether
PD
Pharmacodynamic
PK
Pharmacokinetic
PEGDA
Poly(ethylene glycol) diacrylate
PICO
Poly(itaconate-co-citrate-co-octanediol)
POMaC
Poly(octamethylene maleate (anhydride) citrate)
PC
Polycarbonate
PDMS
Polydimethylsiloxane
PEEK
Polyether ether ketone
PEG
Polyethylene glycol
PET
Polyethylene terephthalate
PETG
Polyethylene terephthalate glycol
PLA
Polylactic acid
PMMA
Polymethylmethacrylate
PP
Polypropylene
PS
Polystyrene
PTFE
Polytetrafluoroethylene
PVC
Polyvinylchloride
PVP
Polyvinylpyrrolidone
RPTEC
Renal proximal tubule epithelial cells
SEM
Scanning electron microscopy
SPC
Statistical process control
SLA
Stereolithography
SEBS
Styrene–ethylene–butylene–styrene
FEPM
Tetrafluoroethylene–propylene
TPE
Thermoplastic elastomer
TPU
Thermoplastic polyurethane
TEER
Transepithelial/transendothelial electrical resistance
XPS
X-ray photoelectron spectroscopy
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