title: Engineering stable topography in dense bio-mimetic 3D collagen scaffolds.
abstract: Topographic features are well known to influence cell behaviour and can provide a powerful tool for engineering complex, functional tissues. This study aimed to investigate the mechanisms of formation of a stable micro-topography on plastic compressed (PC) collagen gels. The uni-directional fluid flow that accompanies PC of collagen gels creates a fluid leaving surface (FLS) and a non-fluid leaving surface (non-FLS). Here we tested the hypothesis that the resulting anisotropy in collagen density and stiffness between FLS and non-FLS would influence the fidelity and stability of micro-grooves patterned on these surfaces. A pattern template of parallel-aligned glass fibres was introduced to the FLS or non-FLS either at the start of the compression or halfway through, when a dense FLS had already formed. Results showed that both early and late patterning of the FLS generated grooves that had depth (25 ±7 µm and 19 ±8 µm, respectively) and width (55 ±11 µm and 50 ±12 µm, respectively) which matched the glass fibre diameter (50 µm). In contrast, early and late patterning of the non-FLS gave much wider (151 ±50 µm and 89 ±14 µm, respectively) and shallower (10 ±2.7 µm and 13 ±3.5 µm, respectively) grooves than expected. The depth to width ratio of the grooves generated on the FLS remained unaltered under static culture conditions over 2 weeks, indicating that grooves were stable under long term active cell-mediated matrix remodelling. These results indicate that the FLS, characterised by a higher matrix collagen density and stiffness than the non-FLS, provides the most favourable mechanical surface for precise engineering of a stable micro-topography in 3D collagen hydrogel scaffolds.
authors.affiliation: Tissue Repair and Engineering Centre, Institute of Orthopaedics, Stanmore Campus, University College London, London HA7 4LP, UK. rehkrab@ucl.ac.uk
authors.forename: T
authors.initials: T
authors.lastname: Alekseeva
authors.forename: E
authors.initials: E
authors.lastname: Hadjipanayi
authors.forename: E A
authors.initials: EA
authors.lastname: Abou Neel
authors.forename: R A
authors.initials: RA
authors.lastname: Brown
mesh_terms: D016880:Anisotropy; D001672:Biocompatible Materials / Q000737:chemistry; D032701:Biomimetics / Q000379:methods*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003094:Collagen / Q000648:ultrastructure*; D019245:Compressive Strength; D055119:Elastic Modulus; D005347:Fibroblasts / Q000648:ultrastructure; D005898:Glass; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008422:Materials Testing / Q000379:methods; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003094:Collagen