Our work investigates how mechanical properties of ECMdirects the immune fate of bone marrow niche cells. The immune system develops in the bone marrow, which is viscoelastic, exhibiting properties of both a solid and fluid. Dr. Vining earned a NIH K08 Mentored Clinical Scientist Career Development Award from the NIDCR to support his Ph.D. in David Mooney’s lab at Harvard University to develop artificial systems with human cells to study how the mechanical resistance of ECM can direct the immune fate of mesenchymal stromal cells (MSCs) (Vining, K.H., et al., 2018). An artificial fibrillar ECM was fabricated with interpenetrating networks of type-I collagen and chemically-modified polysaccharides. Viscoelasticity was specifically tuned independent of other material properties across a physiologic range of bone marrow stiffness. More fluid-like, viscous matrix was associated with immunomodulatory expression of MSCs, which is consistent with homeostasis in healthy bone marrow. Further, collaborative projects have demonstrated how programmable materials can be used to enhance persistence and immunomodulation of MSCs (Mao, A.S., et al., 2019), and to enhance licensing of MSCs for immunomodulation (Pujana-Gonzalez, A., Vining, K.H., et al., 2020).
Vining, K.H., Stafford, A., Mooney, D.J. (2019) Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels. Biomaterials, 188, 187-197. PMCID: 30366219
Mao, A.S., Ozkale, B., Shah, N.J., Vining, K.H., Descombes, T., Zhang, L., Scadden, D.T., Weitz, D.A., Mooney, D.J. (2019) Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation. Proceedings of the National Academy of Science, 116 (31) 15392-15397. PMCID: PMC6681761
Gonzalez-Pujana A*, Vining K.H.*, Zhang DKY, Santos-Vizcaino E, Igartua M, Hernandez RM, Mooney DJ. Multifunctional biomimetic hydrogel systems to boost the immunomodulatory potential of mesenchymal stromal cells. Biomaterials. 2020 Oct;257:120266. PMCID: PMC7477339. *Authors contributed equally