Mechanical and Biological Properties of Bio-Inspired Nano-Fibrous Elastic Materials from Collagen

Abstract

Collagen-based biomaterials have been widely used in medical applications, because of its many advantages, including low antigenicity, abundant availability, biodegradability, and biocompatibility [1]. Collagen represents the major structural protein, accounting for nearly 30% of all vertebrate body protein. The collagen molecule comprises three polypeptide chains (α-chains) which form a unique triple-helical structure (Fig. 1) [2]. Each of the three chains has the repeating structure glycine–X–Y, where X and Y are frequently the imino acids proline and hydroxyproline (Fig. 1b). The collagen molecules self-aggregate through fibrillogenesis into microfibrils forming extracellular matrix (ECM) in the body [3-5]. The fibrils provide the major biomechanical matrix for cell growth (Fig. 1a), allowing the shape of tissues to be defined and maintained. The main application of collagen for biomaterials is as a scaffold for tissue engineering and a carrier for drug delivery [2, 6-9]. Many different forms of collagen biomaterials, such as film [10, 11], gel [12-17], sponge [18-20], micro/nano-particle [21, 22], and fiber [23], have been fabricated and used in practice. However, most collagen biomaterials become brittle and fail under quite low strains, which limit their application to biomedical engineering fields that need larger mechanical properties, especially elasticity [16]. Recently, we reported a novel crosslinking method of improving the mechanical properties and thermal stability of collagen [24]. The method mimics actual biological events to form collagen matrix in the body; monomeric collagens extruded from cells into extracellular environment initially form microfibrillar aggregates, then lysyl oxidase crosslinking during their assembly to form fibrils (Fig. 1). The in vitro crosslinking during collagen fibrillogenesis, namely “bio-inspired crosslinking”, creates a crosslinked collagen fibrillar gel with high mechanical properties at certain crosslinking agent concentrations [25, 26]. Fibril formation involves the aggregation and alignment of collagen molecules, and helps increase the collagen’s thermal stability. The introduction of crosslinking during fibril formation further increases the thermal stability of collagen. The synergistic effects of crosslinking and fibril formation are found to enable an increase in the thermal stability of