We have developed electrospun nanofibrous matrix to mimic the biochemical and topographical characteristics of the basement membrane to synergistically improve the self-renewal and proliferation, while maintaining the phenotype of human hematopoietic stem/progenitor cells (HSPCs) (Chua et al, 2006, 2007, Jiang et al, 2011), and demonstrated the potential of nanofiber-expanded cells for angiogenic therapies in treating heart and limb ischemia and osteoporosis.  We have developed nanofiber matrix as an extrinsic cue to promote preferential differentiation of stem cells and generate functional progenitors and tissue cells for regenerative therapies, including neural stem cells (Christopherson, et al, 2009; Lim, et al, 2010; Mahairaki, et al, 2011), human embryonic stem cell (ESC)-derived neural crest stem cells (Ren, et al, 2012), and human ESC-derived retinal ganglion cells (Slush et al, 2015). We have developed a patented electrostretching method to generate hydrogel microfiber bundles with embedded nanofiber topography using aqueous solutions of natural polymers (Zhang, et al, 2014), and demonstrated its utility as a 3D scaffold with internal alignment cue to induce organized cell/tissue regeneration: electrospun fibrin fibers for arterial vascular engineering (Barreto-Ortiz, 2013; 2015; Elliot, et al, 2019) and skeletal muscle myofiber regeneration (Gilbert-Honick, et al, 2018, 2020; Somers, et al, 2019; Morrissette-McAlmon, et al, 2020).

1. Chua KN, Chai C, Lee PC, Tang YN, Ramakrishna S, Leong KW, Mao HQ. Surface-aminated electrospun nanofibers enhance adhesion and expansion of human umbilical cord blood hematopoietic stem/progenitor cells. Biomaterials. 27(36): 6043–6051 (2006). PMID: 16854459.
2. Christopherson GT, Song H, Mao HQ. The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. Biomaterials. 30(4): 556–564 (2009). PMID: 18977025.
3. Zhang S, Liu X, Barreto-Ortiz SF, Yu Y, Ginn BP, DeSantis NA, Hutton DL, Grayson WL, Cui FZ, Korgel BA, Gerecht S, Mao HQ. Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching. Biomaterials. 35(10): 3243–3251 (2014). PMCID: PMC3923323. PMID: 24439410.
4. Elliott MB, Ginn B, Fukunishi T, Bedja D, Suresh A, Chen T, Inoue T, Dietz HC, Santhanam L, Mao HQ, Hibino N, Gerecht S. Regenerative and durable small-diameter graft as an arterial conduit. Proceedings of the National Academy of Sciences of the United States of America. 116(26): 12710–12719 (2019). PMCID: PMC6601275; PMID: 31182572.