Electrospun porous bilayer nano-fibrous fish collagen/PCL bio-composite scaffolds with covalently cross-linked chitooligosaccharides for full-thickness wound-healing applications.

The development of tissue-engineered biodegradable artificial tissue substitutes with extracellular matrix-mimicking properties that govern the interaction between the material and biological environment is of great interest in wound-healing applications. In the present study, novel bilayer nanofibrous scaffolds composed of fish collagen (FC) and poly(ε-caprolactone) (PCL) were fabricated using electrospinning, with the covalent attachment of chitooligosaccharides (COS) via carbodiimide chemistry. The architecture and fiber diameter of the non-cross-linked nanofibrous scaffolds remained consistent irrespective of the polymer ratio under different electrospinning conditions, but the fiber diameter changed after cross-linking in association with the FC content. Fourier-transform infrared spectroscopy analysis indicated that the blend of biomaterials was homogenous, with an increase in COS levels with increasing FC content in the nanofibrous scaffolds. Based on cytocompatibility analysis (i.e., the cellular response to the nanofibrous scaffolds and their interaction), the nanofibrous scaffolds with high FC content were functionally active in response to normal human dermal fibroblast­neonatal (NHDF-neo) and HaCaT keratinocyte cells, leading to the generation of a very effective tissue-engineered implant for full-thickness wound-healing applications. In addition to these empirical results, an assessment of the hydrophilicity, swelling, and mechanical integrity of the proposed COS-containing FC-rich FC/PCL (FCP) nanofibrous scaffolds confirmed that they have significant potential for use as tissue-engineered skin implants for rapid skin regeneration.