This paper reports a new method of cross-linking electrospun zein fibers using citric acid as a non-toxic cross-linker to enhance the water stability and cytocompatibility of zein fibers for tissue engineering and other medical applications. The electrospun structure has many advantages over other types of structures and protein-based biomaterials possess unique properties preferred for tissue engineering and other medical applications. However, ultrafine fiber matrices developed from proteins have poor mechanical properties and morphological stability in the aqueous environments required for medical applications. Efforts have been made to improve the water stability of electrospun protein scaffolds using cross-linking and other approaches, but the current methods have major limitations, such as cytotoxicity and low efficiency. In this research electrospun zein fibers were cross-linked with citric acid without using any toxic catalysts. The stability of the cross-linked fibers in phosphate-buffered saline and their ability to support the attachment, spreading, and proliferation of mouse fibroblast cells were studied. The cross-linked electrospun fibers retained their ultrafine fibrous structure even after immersion in PBS at 37 °C for up to 15 days. Citric acid cross-linked electrospun zein scaffolds showed better attachment, spreading, and proliferation of fibroblast cells than uncross-linked electrospun zein fibers, cross-linked zein films, and electrospun polylactide fibers.
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