Abstract

A significant body of research has considered collagen as a scaffold material for soft tissue regeneration. The main structural component of extra-cellular matrix (ECM), collagen’s advantages over synthetic polymers are numerous. However, for applications where higher stiffness and stability are required, significant cross-linking may affect bioactivity. A carbodiimide (EDC) cross-linking route consumes carboxylate groups that are key to collagen’s essential cell recognition motifs (GxOGER). Fibrinogen was considered as a promising additive as it plays a key role in the process of wound repair and contains RGD integrin binding sites which bind to a variety of cells, growth factors and cytokines. Fibrinogen’s binding sites however, also contain the same carboxylate groups as collagen. We have successfully produced highly interconnected, porous collagen-fibrinogen scaffolds using a lyophilisation technique and micro-computed tomography demonstrated minimal influence of either fibrinogen content or cross-linking concentration on the scaffold structure. The specific biological effect of fibrinogen additions into cross-linked collagen are considered by using films as a model for the struts of bulk scaffolds. By considering various additions of fibrinogen to the collagen film with increasing degrees of cross-linking, this study demonstrates a significant biological advantage with fibrinogen addition across the cross-linking concentrations typically applied to collagen-based scaffolds.

Highlights

  • A key desire in tissue engineering is to mimic and regenerate the existing native environment.The extra-cellular matrix provides physical support to tissues by occupying the intercellular space and acting as a native scaffolding, but is a highly dynamic, mobile, and flexible structure which is key to cellular behaviour and tissue function [1]

  • By considering various additions have, in a previous study, been shown to exhibit minimal adhesion to collagen films of any cross-linking of fibrinogen to the collagen film with increasing degrees of cross-linking, this study aims to concentration [47]

  • By considering various additions of fibrinogen to the collagen film with increasing investigate whether fibrinogen can impart any biological advantage across the cross-linking degrees of cross-linking, this study aims to investigate whether fibrinogen can impart any biological concentrations typically applied for collagen-based scaffolds

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Summary

Introduction

A key desire in tissue engineering is to mimic and regenerate the existing native environment. The extra-cellular matrix provides physical support to tissues by occupying the intercellular space and acting as a native scaffolding, but is a highly dynamic, mobile, and flexible structure which is key to cellular behaviour and tissue function [1]. Collagen forms the major structural component of this and, as such, there has been a significant focus of research on collagen as a scaffold material for tissue regeneration [2,3,4,5]. GAGs form porous hydrated gels and tend to fill most of the extra-cellular matrix space providing mechanical support to tissues whilst allowing for the migration of cells and diffusion of water soluble molecules [7]

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