Emma McCarthy

Doctoral Researcher
Physical Sciences for Health CDT

Thesis project - "Controlling Collagen Formation in Wounds Using Smart Dressings"

Professor Liam Grover, School of Chemical Engineering
Dr Pola Goldberg-Oppenheimer, School of Chemical Engineering
Dr Iain Styles, School of Computer Science
Dr Alessio Alexiadis, School of Chemical Engineering

This project will identify methods to manipulate the formation of collagen fibrils in a controlled manner, allowing the development of a new generation of dressings for patients with traumatic soft tissue injury. Through developing new methods of structuring surfaces the potential for directing the deposition of extracellular matrix will be investigated.

The functional properties of most connective tissues are determined by the multiscale organisation of the component molecules. Collagen proteins form the majority of connective tissues, with there being 28 different types of proteins known as collagen. Most collagen in skin, bone, ligament, tendons and the cornea is type I collagen. Through self-assembly of procollagen, followed by covalent cross-links, a network of fibres is established in a hierarchical fashion, across molecular and macro-scales. This fibrous network has characteristic features, such as regular D-periodicity and triple helix dimensions, all of which contribute to the overall organisation of the collagen fibres that determines the specific properties most soft tissues in vivo [1].

An example of this is light transmission through the cornea. The arrangement of collagen into a lattice with ~15nm spacing causes scattered light to interfere destructively causing the transparency of the cornea [2]. In comparison, collagen within the skin is arranged in a meshwork, contributing to both mechanical compliance and skin appearance. Disruption of collagen organisation in any tissue leads to the formation of a scar, which can be unsightly or result in corneal blindness. Although encapsulated cells biologically mediate the process of collagen deposition, [3] the subsequent assembly of the collagen network is physically driven. As such it is possible to modify fibril structure by adjusting the local chemical/physical environment. Consequently, there is a significant need to identify methods to modify the hierarchical structure of newly deposited matrix, preferably in a highly tissue dependent manner.

The self-assembly of different collagen types is a physically and chemically driven one. Through in-depth understanding of the molecular processes involved with collagen growth will give an insight into the manipulation of matrix formation. The acquired degree of collagen organisation and control will be characterised using atomic force microscopy, scanning electron microscope, transmission electron microscopy, polarisation lightmicroscopy and scanning laser confocal microscopy. A range of patterning methods will produce micro-to-nano structures ordered across several length scales, with varying pitch, dimensions and aspect ratios. Analysis of collagen deposited upon these surfaces, with respect to its morphological and chemical properties, will be undertaken and compared with a computational model.  Coarse-grained molecular dynamics of collagen formation and will establish a comparison between idealised fibril formation and fibrils in vitro. These surfaces will be created using photolithography, focussed-ion beam milling and electrohydrodynamic patterning. To further investigate the effect of local environments on collagen networks metallic ions will be added to the gelation process alongside the application of external electrical fields due to the fact collagen is a piezoelectric molecule.

A more fundamental understanding of how environments may influence matrix formation will enable the design of better medical devices and may also allow others to identify the cause of a number of diseases where matrix malformation is a major symptom. This will allow dressings to be manufactured which will reproduce these results reducing the damaging effects of pathological scarring.