Peripheral nerve injuries are a significant clinical challenge due to the limited capacity of nerve tissue to regenerate.1 Differentiation of embryonic stem cells (ESCs) in vitro can provide a novel source of cells for neural tissue replacement or repair.1 In order to advance the use of ESCs for clinical practice there is a need to overcome limitations such as: 1) a lack of well-defined, xeno-free culture systems for directed differentiation of ESCs; 2) a lack of systematic control over culture conditions that regulate ESC behavior; 3) inability to produce neurons from ESCs on large scale.2 The Becker Lab has developed a synthetic nanofiber substrate that has demonstrated effective differentiation of mouse ESCs to neural progenitors within one day.3 It is established that multiple bioactive molecules work synergistically to regulate cell function, but there are very few reports describing substrates with more than one attached bioactive group.4 We have reported scaffolds that can be functionalized with two peptides or carbohydrates.4 This research seeks to overcome the limitations mentioned above through the creation of polymer nanofibers functionalized with three peptide sequences (GRGDS, GYIGSR and FGL) for directed differentiation of ESCs into neural lineage and development of mature neural cells. Poly(ε-caprolactone-co-2-oxepane-1,5-dione) functionalized with 4-dibenzocyclooctynol was successfully synthesized and used for creation of random and aligned nanofibers using electrospinning. Surface functionalization of nanofiber scaffolds with three peptides was performed using strain-promoted alkyne-azide cycloaddition, oxime ligation and thiol-ene “click” chemistry. Study on differentiation of mouse ESCs to neural lineage is ongoing. The developed substrates can be extended for controlled differentiation and maturity of other lineages. References 1) Daly, W. et al. J. R. Soc. Interface 2012, 9, 202-221. 2) Brafman, D.A. et al. Biomaterials 2010, 31(34), 9135-44. 3) Callahan, L.A. et al. Biomaterials 2013, 34(36), 9089-95. 4) Zheng, J. et al. Biomacromolecules 2015, 16, 357-563.

Functionalized nanofiber scaffolds for nerve regeneration

251st National Meeting (2016)

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