Abstract
Biological materials found in living organisms, many of which are proteins, feature a complex hierarchical organization. Type I collagen, a fibrous structural protein ubiquitous in the mammalian body, provides a striking example of such a hierarchical material, with peculiar architectural features ranging from the amino acid sequence at the nanoscale (primary structure) up to the assembly of fibrils (quaternary structure) and fibers, with lengths of the order of microns. Collagen plays a dominant role in maintaining the biological and structural integrity of various tissues and organs, such as bone, skin, tendons, blood vessels, and cartilage. Thus, “artificial” collagen-based fibrous assemblies, endowed with appropriate structural properties, represent ideal substrates for the development of devices for tissue engineering applications. In recent years, with the ultimate goal of developing three-dimensional scaffolds with optimal bioactivity able to promote both regeneration and functional recovery of a damaged tissue, numerous studies focused on the capability to finely modulate the scaffold architecture at the microscale and the nanoscale in order to closely mimic the hierarchical features of the extracellular matrix and, in particular, the natural patterning of collagen. All of these studies clearly show that the accurate characterization of the collagen structure at the submolecular and supramolecular levels is pivotal to the understanding of the relationships between the nanostructural/microstructural properties of the fabricated scaffold and its macroscopic performance. Several studies also demonstrate that the selected processing, including any crosslinking and/or sterilization treatments, can strongly affect the architecture of collagen at various length scales. The aim of this review is to highlight the most recent findings on the development of collagen-based scaffolds with optimized properties for tissue engineering. The optimization of the scaffolds is particularly related to the modulation of the collagen architecture, which, in turn, impacts on the achieved bioactivity.
Highlights
Biological tissues are made of cells embedded in a tissue-specific extracellular matrix (ECM)
While the ECM was originally thought as a passive system responsible for the structural and functional integrity of tissues and organs, it is clear that the ECM plays a pivotal role as an active regulator of cell phenotype (Birk and Bruckner, 2011; Pawelec et al, 2016)
After presenting the structural hierarchy of type I collagen in tissues and discussing the related biological activity, we address the most recent findings on the development of collagen-based scaffolds with optimized regenerative capability
Summary
Biological tissues are made of cells embedded in a tissue-specific extracellular matrix (ECM). The ECM is an intricate network of macromolecules, including proteins, glycosaminoglycans, proteoglycans, and glycoproteins, which are able to hold a high amount of water (Gelse et al, 2003; Birk and Bruckner, 2011). This provides the ECM with gel-like texture and gel-like mechanical properties. Cell surface receptors recognize specific ligands on the ECM, attach to them, and transduce signals from the ECM This type of signaling, including biochemical, topographical, and mechanical cues, regulates various cell functions, such as cellular growth, migration, and differentiation. It can be stated that cells and ECM constitute a highly dynamic and finely regulated system that controls the development, maintenance, and repair of tissues and organs
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