Dense Collagen Materials and the Modulation of Fibrillogenesis for Tissue Engineering

Abstract

Native tissues regulate cell behaviour through a finely balanced interplay of biochemical and mechanical cues that synthetic materials and nylon membranes cannot reproduce. This thesis presents a platform of densified collagen scaffolds that bridges the gap between synthetic materials and living tissue. A scalable, material-based absorptive-deformation process removes interstitial water from neutralised type I collagen in a single step, concentrating the matrix more than twenty-fold, axially aligning fibrils and producing mechanically robust constructs. Shaped in a conical mould, the method yields seamless tubes whose lumen diameter and wall thickness can be adjusted independently. Uncrosslinked rat-calibre grafts tolerate arterial pressures, remain patent for 17 weeks after end-to-end aortic implantation and show progressive cellular infiltration without thrombosis. The fabrication scales to porcine dimensions without loss of mechanical strength or suture integrity, underscoring its translational potential. Planar densification of the same matrix produces thin sheets that serve as a platform for fibrillogenesis-modulation studies. Incorporating ionic compounds, macromolecular crowders and other biomolecules during compaction tunes fibril diameter, interfibrillar spacing and stiffness across the 5-15 kPa window characteristic of basement membranes, all without chemical crosslinkers. Hyaluronic-modified sheets support keratinocyte adhesion, radial migration and stratification from full-thickness mouse oesophageal explants, challenging rigid nylon culture inserts as more biomimetic substrates in vitro, while sodium-sulphate-enhanced sheets integrate well in vivo, exhibiting host-cell infiltration and early neovascularisation without adverse fibrosis. Overall, this scalable absorptive-deformation method produces robust collagen tubes and adaptable sheets in a single platform to better mimic real tissue, opening the way to superior vascular grafts, realistic lab-grown tissue models, and studies of how cells respond to mechanical cues.