Aliphatic Chain Modification of Collagen Type I: Development of Elastomeric, Compliant, and Suturable Scaffolds

Collagen type I is one of the most suitable natural biomaterials for constructing tissue-engineering scaffolds. Despite their biocompositional similarities to physiological tissues, these scaffolds lack host specific and matching mechanical properties. While it is possible to enhance their stiffness by cross-linking, it often compromises their abilities to expand or strain under minimal stress, that is, compliance (inverse of stiffness). Here, we report a simple, inexpensive, cross-linking-and elastin-free collagen-based material composition for developing elastomeric scaffolds that are highly compliant, soft yet strong, and suturable, therefore, clinically attractive. Our strategy utilizes roomerature modification of collagen type I scaffolds with linear aliphatic chains of various lengths (C7-C18). In particular, dodecenylsuccinic anhydride (size: C12, DDSA) modified scaffolds elongated up to 400% of its initial length compared to only ∼20% for collagen-control within the applied tensile stress of 0.2 MPa without breaking. Furthermore, the suture retention strength value increased to 60 g-force from 30 g-force for collagen control. We confirmed that the C12-modified material remained structurally stable at the physiological temperature (37 °C) with a tan δvalue of ∼0.3, similar to collagen control; however, tan δincreased sharply for C12-modified collagen above 42 °C, compared to 59 °C for collagen control. To understand the mechanism of hyperextensibility, we studied the morphology of the resultant material by transmission electron microscopy (TEM), which showed an altered microstructure of C12-modified collagen scaffolds. While the partially C12-modified sample had a mixture of typical collagen type I triple helix and diffused gelatinized random coil-like configuration, the fully modified samples showed thick wrinkled and entangled ribbon-like microstructures, which was different than that of thermally denatured gelatin. We further confirmed that the resultant material allowed cell growth in vitro and in vivo in a subcutaneous mouse model.