Adaptable Manufacturing and Biofabrication of Milliscale Organ Chips With Perfusable Vascular Beds

Microphysiological systems (MPS) containing perfusable vascular beds unlock the ability to model tissue-scale elements of vascular physiology and disease in vitro. Access to inexpensive stereolithography (SLA) 3D printers now enables benchtop fabrication of polydimethylsiloxane (PDMS) organ chips, eliminating the need for cleanroom access and microfabrication expertise, and can facilitate broader adoption of MPS approaches in preclinical research. Rapid prototyping of organ chip mold designs accelerates the processes of design, testing, and iteration, but geometric distortion and surface roughness of SLA resin prints can impede the development of standardizable manufacturing workflows. This study reports postprocessing procedures for manufacturing SLA-printed molds that produce fully cured, flat, patently bonded, and optically clear polydimethyl siloxane (PDMS) organ chips. Injection loading tests were conducted to identify milliscale membrane-free organ chip (MFOC) designs that allowed reproducible device loading by target end-users, a key requirement for broad nonexpert adoption in preclinical research. The optimized milliscale MFOC design was used to develop tissue engineering protocols for (i) driving bulk tissue vasculogenesis in MFOC, and (ii) seeding the bulk tissue interfaces with a confluent endothelium to stimulate self-assembly of perfusable anastomoses with the internal vasculature. Comparison of rocker- and pump-based protocols for flow-conditioning of anastomosed vascular beds revealed that continuous pump-driven flow is required for reproducible barrier maturation throughout the 3D tissue bulk. Demonstrated applications include nanoparticle perfusion and engineering perfusable tumor vasculature. These easily adaptable methods for designing and fabricating vascularized microphysiological systems can accelerate their adoption in a diverse range of preclinical laboratory settings.