Extracellular Matrix Microenvironments that Modulate Angiogenesis or Cell Fate Commitment
We are broadly interested in manipulating the extracellular matrix (ECM) microenvironment to induce cell fate commitment or to modulate other cellular functions. Some of the ECM properties of interest include the ECM chemical composition, topographical patterning, and rigidity. We are developing oriented nano-scale and micro-scale biomaterials that guide cell organization and modulates cell function. We hypothesize that spatially patterned biomaterials can alter cytoskeletal tension and chromatin remodeling to influence cell fate. We are also engineering high-throughput approaches for testing combinatorial ECM compositions and rigidities that favor cell fate commitment of induced pluripotent stem cells towards cardiovascular lineages.
1. Hou L, Coller J, Natu V, Hastie TJ, Huang NF. Combinatorial Extracellular Matrix Microenvironments Promote Survival and Phenotype of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells in Hypoxia. Acta Biomater. Epub.
2. Huang NF, Patlolla B, Abilez O, Sharma H, Rajadas J, Beygui RE, Zarins CK, Cooke JP. A matrix micropatterning platform for cell localization and stem cell fate determination. Acta Biomater. 6:4614-21, 2010.
Mechanotransduction Pathways that Induce Cell Fate Commitment
Using customizable ECM microenvironments, we are interested in studying mechanotransduction pathways that induce cell fate commitment. Some of the mechanotransduction pathways of interest include those that are activated by integrins, focal adhesions, and actin-binding proteins. Current projects include mechanotransduction pathways that are involved cardiovascular differentiation of induced pluripotent stem cells, direct transdifferentiation of fibroblasts into cardiovascular lineages, and reprogramming of fibroblasts into induced pluripotent stem cells.
1. Nakayama KH, Hong G, Lee JC, Patel J, Edwards B, Zaitseva TS, Paukshto MV, Dai H, Cooke JP, Woo YJ, Huang NF. Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis. ACS Nano 9: 6900–6908, 2015.
2. Nakayama KH, Surya VN, Gole M, Walker TW, Yang W, Lai ES, Ostrowski MA, Fuller GG, Dunn AR, Huang NF. Nanoscale Patterning of Extracellular Matrix Alters Endothelial Function under Shear Stress. Nano Lett, 16:410-9, 2016.
Tissue Engineering and Regenerative Medicine
By gaining fundamental insights in the role of ECM-mediated mechanotransduction pathways on cell fate commitment, we will engineer three-dimensional vascular conduits, cardiac patches, and skeletal muscle grafts with physiologically relevant cellular and ECM compositions. We are also working with industry partners to engineer nanofibrillar scaffolds that can induce angiogenesis or lymphangiogenesis.
1. Mulyasasmita W, Cai L, Dewi RE, Jha A, Ullmann SD, Luong RH, Huang NF, Heilshorn SC. Avidity-controlled hydrogels for injectable co-delivery of induced pluripotent stem cell-derived endothelial cells and growth factors. J Control Release 191:71-81, 2014.
2. Burridge PW, Metzler SA, Nakayama K, Abilez OJ, Simmons CS, Bruce MA, Matsuura Y, Kim P, Wu JC, Butte M, Huang NF#, Yang PC. Multi-cellular Interactions Sustain Long-Term Contractility of Human Pluripotent Stem Cell-Derived Cardiomyocytes. Am J Trans Res, 6:724-735, 2014.
3. Nakayama KH, Joshi PA, Lai ES, Gujar P, Joubert L-M, Chen B, Huang NF. Bi-layered vascular graft derived from human induced pluripotent stem cells with biomimetic structure and function. Regen Med 10:745-55, 2015.
4. Hadamitzky C, Zaitseva TS, Bazalova-Carter M, Paukshto MV, Hou L, Strassberg Z, Ferguson J, Matsuura Y, Dash R, Yang PC, Kretchetov S, Vogt PM, Rockson SG, Cooke JP, Huang NF. Aligned nanofibrillar collagen scaffolds - Guiding lymphangiogenesis for treatment of acquired lymphedema. Biomaterials 102:259-67, 2016.