Development of photo-crosslinkable collagen hydrogel building blocks for vascular tissue engineering applications: A superior alternative to methacrylated gelatin?

Abstract

The present work targets the development of collagen-based hydrogel precursors, functionalized with photo-crosslinkable methacrylamide moieties (COL-MA), for vascular tissue engineering (vTE) applications. The developed materials were physico-chemically characterized in terms of crosslinking kinetics, degree of modification/conversion, swelling behavior, mechanical properties and in vitro cytocompatibility. The collagen derivatives were benchmarked to methacrylamide-modified gelatin (GEL-MA), due to its proven track record in the field of tissue engineering. To the best of our knowledge, this is the first paper in its kind comparing these two methacrylated biopolymers for vTE applications. For both gelatin and collagen, two derivatives with varying degrees of substitutions (DS) were developed by altering the added amount of methacrylic anhydride (MeAnH). This led to photo-crosslinkable derivatives with a DS of 74 and 96% for collagen, and a DS of 73 and 99% for gelatin. The developed derivatives showed high gel fractions (i.e. 74% and 84%, for the gelatin derivatives; 87 and 83%, for the collagen derivatives) and an excellent crosslinking efficiency. Furthermore, the results indicated that the functionalization of collagen led to hydrogels with tunable mechanical properties (i.e. storage moduli of [4.8-9.4 kPa] for the developed COL-MAs versus [3.9-8.4 kPa] for the developed GEL-MAs) along with superior cell-biomaterial interactions when compared to GEL-MA. Moreover, the developed photo-crosslinkable collagens showed superior mechanical properties compared to extracted native collagen. Therefore, the developed photo-crosslinkable collagens demonstrate great potential as biomaterials for vTE applications.

Keywords: Methacrylamide-modified collagen; Methacrylamide-modified gelatin; Photo-crosslinkable hydrogels; Vascular tissue engineering.