Biomedical Engineering Reference
In-Depth Information
13
Mechanical and Biological Properties of
Bio-Inspired Nano-Fibrous Elastic
Materials from Collagen
Nobuhiro Nagai
1,2
, Ryosuke Kubota
2
,
Ryohei Okahashi
2
and Masanobu Munekata
2
1
Division of Clinical Cell Therapy, Center for Advanced Medical Research and
Development, ART, Tohoku University, Graduate School of Medicine
2
Division of Biotechnology and Macromolecular Chemistry, Graduate
School of Engineering, Hokkaido University
Japan
1. Introduction
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
