An investigation of common crosslinking agents on the stability of electrospun collagen scaffolds

Electrospinning is a widely used processing method to form fibrous tissue engineering scaffolds that mimic the structural features of the native extracellular matrix. Electrospun fibers made of collagen have been sought because it is a natural structural protein that supports cell attachment and growth. Yet, conventional solvents used to electrospin collagen can result in the loss of hydrolytic stability and fiber morphology of the scaffold. This study evaluated the effect of commonly used synthetic and natural crosslinking agents, genipin, glutaraldehyde, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), and EDC with N-hydroxysulfosuccinimide (EDC–NHS), on electrospun collagen. Crosslinked collagen scaffolds were assessed for structural integrity in an in vitro immersion study for up to 3 months. Their cytocompatibility was evaluated by human mesenchymal stem cell morphology and proliferation. Our results showed that dimensional stability and cytocompatibility of crosslinked electrospun collagen scaffolds are dependent on the type of crosslinking agent used. Collagen scaffolds treated with EDC and EDC–NHS were structurally stable and retained fiber structure for up to 3 months and were cytocompatible. Therefore, EDC and EDC–NHS are favorable crosslinking agents for electrospun collagen that can be utilized in tissue engineering applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 762–771, 2015.