Routes towards Novel Collagen-Like Biomaterials

Abstract

Collagen plays a major role in providing mechanical support within the extracellular matrix and thus has long been used for various biomedical purposes. Exemplary, it is able to replace damaged tissues without causing adverse reactions in the receiving patient. Today's collagen grafts mostly are made of decellularized and otherwise processed animal tissue and therefore carry the risk of unwanted side effects and limited mechanical strength, which makes them unsuitable for some applications e.g., within tissue engineering. In order to improve collagen-based biomaterials, recent advances have been made to process soluble collagen through nature-inspired silk-like spinning processes and to overcome the difficulties in providing adequate amounts of source material by manufacturing collagen-like proteins through biotechnological methods and peptide synthesis. Since these methods also open up possibilities to incorporate additional functional domains into the collagen, we discuss one of the best-performing collagen-like type of proteins, which already have additional functional domains in the natural blueprint, the marine mussel byssus collagens, providing inspiration for novel biomaterials based on collagen-silk hybrid proteins.

Recent Advances in Collagen Mimetic Peptide Structure and Design

“…Temperature prediction algorithms as a tool for designing heterotrimers will be explored, as well as the use of CMPs to study natural collagen sequences and diseases. Topics such as collagen targeting, , protein interactions with collagen, − higher order assemblies of CMPs, − collagen biomaterials, ,, and peptide–polymer conjugates − have been reviewed recently and are therefore outside the scope of this Perspective.…”

Enhanced Collagen-like Protein for Facile Biomaterial Fabrication

“…Since many collagen sequences tend to form gels at higher molecular weights, CMP synthesis has been reported to suffer from problems related to limited solubility and aggregation as the molecular weight of the CMP increases. Increasing the molecular weight via chemical ligation has been used to increase the low thermal stability of CMPs but has been shown to reduce the molecular weight homogeneity of the resulting proteins …”

“…Several bacterial genomes have been found to contain multiple collagen-like sequences that may have arisen from horizontal gene transfer from eukaryotes to bacteria. − Recombinant systems have allowed for the in-depth characterization and manipulation of such bacterial collagen proteins. For example, Streptococcus pyogenes, a Gram-positive bacterium, is known to produce a cell surface collagen-like protein known as Scl2 that may help pathogenic bacteria adhere to animal cells. − Sc12 has been found to possess an acidic, highly charged collagen-like (CL) domain that consists of a repeating amino acid triplet Gly–Xaa–Yaa, characteristic of collagen, that is bracketed by an N-terminal assembly domain (V) and a C-terminal transmembrane domain. ,, Notably, the CL domain is highly charged, and in the absence of hydroxyproline, the triple helix structure is stabilized via the formation of intermolecular salt-bridges between charged amino acids. , Subdomains of the Sc12 CL domain have been expressed individually as both homodimers and homotrimers fused with the N-terminal V domain to form stable helical structures, and their stabilities have been found to be dependent upon amino acid composition, sequence lengths, and mutation location in the native sequence. , Various short amino acid sequences derived from human collagen have been successfully inserted into the Sc12 domain such as fibronectin, heparin, and MMPs. − It has been previously shown that Sc12 constructs can be expressed in E. coli and purified and that the expressed constructs form stable triple helical structures with a melting temperature ( T m ) of 36–38 °C, close to the stability found in human collagens, − , and that these systems can self-assemble into higher-order fibrillar structures .…”

“…Increasing the molecular weight via chemical ligation has been used to increase the low thermal stability of CMPs but has been shown to reduce the molecular weight homogeneity of the resulting proteins. 12 As an alternative, recombinant collagen and collagen-like proteins can be produced recombinantly. 13 In particular, human recombinant collagen (hRC) is favorable as it can be produced in a highly pure, native-like state and therefore presumably would have optimal biocompatibility.…”

“…37,42,43 Notably, the CL domain is highly charged, and in the absence of hydroxyproline, the triple helix structure is stabilized via the formation of intermolecular salt-bridges between charged amino acids. 4,12 Subdomains of the Sc12 CL domain have been expressed individually as both homodimers and homotrimers fused with the N-terminal V domain to form stable helical structures, and their stabilities have been found to be dependent upon amino acid composition, sequence lengths, and mutation location in the native sequence. 43,44 Various short amino acid sequences derived from human collagen have been successfully inserted into the Sc12 domain such as fibronectin, heparin, and MMPs.…”