Mechanically Mutable Matrices: A Hierarchical Investigation of Decellularized Sea Cucumber Collagen as an Adaptable Scaffold Material

ABSTRACT The mechanical mutability of sea cucumbers is a source of bioinspiration for different stimuli‐responsive materials for biomedical applications, soft robotics, self‐healing hydrogels, and tunable scaffolds. However, using the source material itself has rarely been explored. Here, the structure‐function relationships of decellularized mutable collagenous tissue (MCT) from sea cucumbers are investigated, for their potential use as a tissue scaffold material. Given the harsh decellularization process, this necessitated an in‐depth investigation of decellularized MCT (dMCT) vis‐à‐vis native MCT (nMCT). Thus, a cross‐disciplinary hierarchical investigation was performed, utilizing multi‐length scale techniques to study the molecular, fibrillar, and bulk tissue composition and structure within the native and decellularized MCTs. Results highlight a similar composition and structure within 2D sections of both tissues; however, a 3D analysis of fibrillar orientation suggests an increase in the overall percentage of ordered fibrils of the dMCT. Moreover, a dramatic increase in bulk tissue stiffness was observed via rheology, supporting a previously described protein‐based mechanism of mechanical mutability. Finally, cell biocompatibility studies demonstrate that decellularized MCT is not toxic to living cells. Given the retention of native structure, cytocompatibility, and demonstration of modified mechanics following decellularization, MCT shows exceptional promise as an adaptable scaffold for tissue engineering applications.