Review collagen-based biomaterials for wound healing

Abstract

With its wide distribution in soft and hard connective tissues, collagen is the most abundant of animal proteins. In vitro, natural collagen can be formed into highly organized, three-dimensional scaffolds that are intrinsically biocompatible, biodegradable, nontoxic upon exogenous application, and endowed with high tensile strength. These attributes make collagen the material of choice for wound healing and tissue engineering applications. In this article, we review the structure and molecular interactions of collagen in vivo; the recent use of natural collagen in sponges, injectables, films and membranes, dressings, and skin grafts; and the on-going development of synthetic collagen mimetic peptides as pylons to anchor cytoactive agents in wound beds.

Keywords: biocompatible; biodegradable; catgut; extracellular matrix; regenerative medicine.

Figure 1

Sir Joseph Lister (English) and Sir William Macewen (Scottish), pioneers in the use of exogenous collagen in medicine.^,, The image of Lister is from an oil painting by Walter William Ouless (courtesy of the Wellcome Library, London); the image of Macewen is from an oil painting by Charles R. Dowell (courtesy of the Royal College of Physicians and Surgeons of Glasgow). The catgut in oil was prepared by Lister in 1875 (courtesy of King's College London).

Figure 2

Structure of triple-helical collagen. Hydrogen bonds, blue dashed lines; n→π* interactions, red dashed lines. Panel A is a cross-section from PDB entry 1v4f.

Figure 3

Biosynthetic route to collagen fibers. Size and complexity increase upon post-translational modification and self-assembly. The oxidation of lysine side chains leads to the spontaneous formation of hydroxylysyl pyridinoline and lysyl pyridinoline cross-links.

Figure 4

Pyrrolidine ring puckers preferred in the Xaa and Yaa positions of collagen strands, and natural and non-natural derivatives of proline with those preferences. The pyrrolidine rings actually prefer a twist rather than envelope conformation. As C^γ typically experiences the largest out-of-plane displacement in these twisted rings, we refer to pyrrolidine ring conformations simply as “C^γ-exo” and “C^γ-endo”.

Figure 5

Strategy for anchoring molecules in a wound bed. A natural strand (yellow) in weak or damaged collagen is displaced by a synthetic collagen mimetic peptide (CMP; red) that forms a hyperstable triple helix. A pendant dye enables wound assessment; a pendant growth factor expedites wound healing.