ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

FROM CELL CONTRACTILITY
TO CURVATURE-CONTROLLED TISSUE GROWTH
C.M. Bidan 1 , P. Kollmannsberger 1 , K.P. Kommareddy 1 , M. Rumpler 2 ,
Y.J.M. Bréchet 3 , P. Fratzl 1 , J.W.C. Dunlop 1 .
1. ABSTRACT
Many biological processes such as morphogenesis, wound healing and bone
remodelling involve the formation of new tissue. Although the substrate topography has
long been recognized to play a role on the behaviour of individual cells, it is not clear
how larger geometrical features influence biological events at larger scales such as
tissue deposition.
We address this question by culturing tissue-forming osteoblasts on 2mm-thick
hydroxyapatite scaffolds containing pores of different well-defined geometries. Tissue
growth is quantified over 4 weeks by looking through the pores and measuring the
projected tissue area on phase contrast images. Thick tissue is observed in concave
corners but no growth occurs on convex surfaces. Computer simulations show that the
evolution of the tissue/medium interface can be described as a curvature-driven process.
As cells adhere and contract, they generate actin fibres between adhesion sites. Tissue
growth can therefore be illustrated by chords assembled along a curved surface,
representing the deposition of a collection of cells. By demonstrating the local
equivalence between curvature-controlled growth and the interfacial motion due to
tensile chords laid down on a curved surface, we link the cellular response to geometry
with the macroscopic pattern of growth.
Our model quantitatively describes the growth patterns obtained in-vitro in circular
pores and semi-circular channels, which are similar to osteonal and hemi-osteonal
organisation in bone. This implies that geometry is a determining signal for bone
remodelling. Additionally, the different growth rates predicted in various shapes suggest
geometry as an important criterion for scaffold design in tissue engineering.
2. INTRODUCTION
Several studies have been performed to understand the behaviour of individual cells
during biological processes that involve the formation of new tissue, such as
morphogenesis, wound healing and bone remodelling. It has also been shown that cells
1 Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany
2 Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre
Meidling, 1th Medical Department, Hanusch Hospital, Vienna, Austria
3 Materials and Processes Science and Engineering Laboratory (SIMaP), 38402 St Martin d’Hères, France