Biomaterial control of multicellular assembly

vasculogenesis endothelial cells networks multicellular self-assembly

Self-assembled networks of endothelial cells on synthetic fibers.

Vasculogenesis is the process by which endothelial progenitor cells self-assemble into multicellular, blood-bearing fluidic networks throughout our bodies. If properly harnessed in vitro, this process could facilitate the rapid vascularization of biomaterials, a significant outstanding challenge in the field of tissue engineering and regenerative medicine. We utilize biomaterials, microfabrication, and cell force measurements to understand how endothelial cells utilize intercellular mechanical communication to intelligently organize across significant spatial distances into complex multicellular structures. The overall objective of this work is to understand the role of ECM physical properties, specifically fibrous microstructure, in 1) regulating the self-assembly of endothelial cells into a mature vascular network and 2) promoting host cell invasion and integration with host vasculature upon implantation.

Relevant recent publications:

vasculo - bottom - left.jpg

We study how cell traction forces transmitted through the matrix to neighboring cells mediates vasculogenic assembly.

Trainees:  Christopher Davidson, Samuel DePalma
Collaborators:  Andrew Putnam, Adam Helms
Relevant publications:
Physiologic biomechanics enhance reproducible contractile development in a stem cell derived cardiac muscle platform
Tsan YC, DePalma SJ, Zhao YT, Capilnasiu A, Wu YW, Elder B, Panse I, Ufford K, Matera DL, Friedline S, O'Leary TS, Wubshet N, Ho KKY, Previs MJ, Nordsletten D, Isom LL, Baker BM, Liu AP, Helms AS.
Nature Communications. 2021 Oct 25;12(1):6167. PMID: 34697315; PMCID: PMC8546060.
Stromal cell identity modulates vascular morphogenesis in a microvasculature-on-a-chip platform
Margolis EA, Cleveland DS, Kong YP, Beamish JA, Wang WY, Baker BM, Putnam AJ.
Lab on a Chip, 2021 Mar 21;21(6):1150-1163. PMID: 33538719; PMCID: PMC7990720.
Microenvironmental determinants of organized iPSC-cardiomyocyte tissues on synthetic fibrous matrices
DePalma SJ, Davidson CD, Stis AE, Helms AS, Baker BM.
Biomaterials Science, 2021 Jan 5;9(1):93-107. PMID: 33325920; PMCID: PMC7971708.
Fiber crimp confers matrix mechanical nonlinearity, regulates endothelial cell mechanosensing, and promotes microvascular network formation
Davidson CD, Jayco DKP, Wang WY, Shikanov A, Baker BM.
Journal of Biomechanical Engineering, 2020, 142(11).
Cell force-mediated matrix reorganization underlies multicellular network assembly

Davidson CD, Wang WY, Zaimi I, Jayco DKP, Baker BM.

Scientific Reports, 2019, 9(1):12.