www.advhealthmat.de www.MaterialsViews.com FULL PAPER 186 wileyonlinelibrary.com © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Geometry as a Factor for Tissue Growth: Towards Shape Optimization of Tissue Engineering Scaffolds Cécile M. Bidan, Krishna P. Kommareddy, Monika Rumpler, Philip Kollmannsberger, Peter Fratzl,* and John W. C. Dunlop Scaffolds for tissue engineering are usually designed to support cell viability with large adhesion surfaces and high permeability to nutrients and oxygen. Recent experiments support the idea that, in addition to surface roughness, elasticity and chemistry, the macroscopic geometry of the substrate also con- tributes to control the kinetics of tissue deposition. In this study, a previously proposed model for the behavior of osteoblasts on curved surfaces is used to predict the growth of bone matrix tissue in pores of different shapes. These predictions are compared to in vitro experiments with MC3T3-E1 pre-osteob- last cells cultivated in two-millimeter thick hydroxyapatite plates containing prismatic pores with square- or cross-shaped sections. The amount and shape of the tissue formed in the pores measured by phase contrast micro- scopy confirms the predictions of the model. In cross-shaped pores, the ini- tial overall tissue deposition is twice as fast as in square-shaped pores. These results suggest that the optimization of pore shapes may improve the speed of ingrowth of bone tissue into porous scaffolds. of cell and tissue responses and to design optimal scaffolds for in vivo experiments and applications. Cells are known to adapt to the phys- ical properties of their surroundings by integrating the mechanical equilibrium established at their adhesion sites. [5] The resulting mechanical cue is translated into a biochemical signal that triggers bio- logical decisions of the cells. [6] As cells are mechanically attached to each other, either directly or via their extracellular matrix, they are also able to synchronize their response on a larger scale. For example, patterning in cell differentiation arises as a response to stiffness [7] or strain [8] pat- terns, and the distribution of proliferation activity also correlates with the stress dis- tribution in a layer of cells. [9] Cell fate has also been investigated in three-dimensional artificial scaffolds. Adhesion, proliferation, differentiation and mineralization of cells and tissues have been compared in several scaffolds with varying structures. [10,11] Recently, Kumar et al. [12] showed that gene expression, and thus cell differentiation, is more affected by the structural properties of the substrate than by its com- position. Furthermore, pore size and porosity need to satisfy the compromise between a high permeability that enables cell migration and nutrient diffusion within the scaffold, and a large surface area for cell adhesion and extracellular matrix production. [3] Many fabrication processes produce structures with random pores in a large range of sizes and interconnec- tivities difficult to control. Rapid prototyping techniques are much more accurate in that respect. [13] The direct printing of the scaffold enables to control the architecture and thus many mechanical properties of the structure. Rumpler et al. [14] used rapid prototyping to build artificial macro-pores of different controlled geometries and showed that cells locally respond to high curvature by producing tissue. Their hypothesis of local tissue growth proportional to curvature has been confirmed experimentally, not only in pores but also on open surfaces, [15] however with the additional observation that tissue does not grow on convexities. The interfacial evolution derived from a curvature-driven tissue growth model matched the experimental observations as well as the in vivo expecta- tions when comparing with the typical geometries involved in 1. Introduction Three-dimensional scaffolds are needed for tissue engineering applications and may also help to study the effect of the environ- ment on tissue growth in vitro. The material used, [1] the fabrica- tion process, [2] and the architecture of the scaffold [3,4] are known to influence the biological interactions with the host organism. Although all these parameters are difficult to decouple, quanti- fying their effects in vitro is necessary to understand the nature DOI: 10.1002/adhm.201200159 C. M. Bidan, Dr. K. P. Kommareddy, Dr. P. Kollmannsberger, Prof. P. Fratzl, Dr. J. W. C. Dunlop Department of Biomaterials Max Planck Institute of Colloids and Interfaces 14424 Potsdam, Germany E-mail: peter.fratzl@mpikg.mpg.de Dr. M. Rumpler Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling 1th Medical Department Hanusch Hospital, Vienna, Austria Dr. P. Kollmannsberger Department of Health Sciences and Technology (D-HEST) ETH Zurich, 8093 Zurich, Switzerland Adv. Healthcare Mater. 2013, 2, 186–194