Pneumatically Actuated Soft Micromold Device for Fabricating Collagen and Matrigel Microparticles

Soft Robot. 2017 Dec;4(4):390-399. doi: 10.1089/soro.2016.0073. Epub 2017 Jun 27.

Abstract

Collagen microparticles have recently gained more attention as viable cell confinement blocks in many biomedical research fields. Small volume and high surface area of collagen structure improve cell confinement, viability, and proliferation. Moreover, dense collagen fiber structure can protect cells from immune destruction. The ability to produce collagen microparticles in an accurate and reliable way is of upmost importance to the advancement of many biomedical researches, especially cancer research and tissue engineering. Currently, no such fabrication technique exists due to inherent fragility of collagen. Herein, we report the very first platform, pneumatically actuated soft micromold (PASMO) device, which addresses challenges in collagen microparticle production. Our new platform uses a soft micromold with a pneumatic actuator that can produce arbitrary shapes of collagen microstructures precisely from 100 μm to over 2 mm in range and can encapsulate cells inside without damaging the shape. The duplication accuracy of more than 96% in dimensions and 90% in depth has been demonstrated. The density of collagen fiber distribution is determined to be 86.57%, which is higher than that of collagen microparticles produced by other methods. We have confirmed cell viability in collagen microparticles. We also produce Matrigel™ particles as tool to develop a xenograft cancer model. The results demonstrate that Matrigel particles created by the PASMO device can reduce cell scattering for the xenograft model and the uniformity of tumors developed in mice is 12-fold improved, which can lead to an increased accuracy of cancer metastasis studies and drug screening research. These breakthroughs in the production of modular microparticles will push the boundaries of cancer research in the near future.

Keywords: cancer xenograft; collagen and Matrigel; microenvironment; pneumatic actuation.