The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth Anthony C. Jones a , Christoph H. Arns a , Dietmar W. Hutmacher b , Bruce K. Milthorpe c , Adrian P. Sheppard a , Mark A. Knackstedt a, * a Department of Applied Mathematics, Research School of Physical Sciences and Engineering, Australian National University, Canberra ACT 0200, Australia b Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland 4059, Australia c Graduate School of Biomedical Engineering, University of New South Wales, Sydney 2052, Australia article info Article history: Received 16 September 2008 Accepted 16 October 2008 Available online 16 December 2008 Keywords: Bone ingrowth Hydroxyapatite Scaffold Porosity Microstructure Elasticity abstract In the design of tissue engineering scaffolds, design parameters including pore size, shape and inter- connectivity, mechanical properties and transport properties should be optimized to maximize successful inducement of bone ingrowth. In this paper we describe a 3D micro-CT and pore partitioning study to derive pore scale parameters including pore radius distribution, accessible radius, throat radius, and connectivity over the pore space of the tissue engineered constructs. These pore scale descriptors are correlated to bone ingrowth into the scaffolds. Quantitative and visual comparisons show a strong correlation between the local accessible pore radius and bone ingrowth; for well connected samples a cutoff accessible pore radius of w100 mM is observed for ingrowth. The elastic properties of different types of scaffolds are simulated and can be described by standard cellular solids theory: (E/E 0 ) ¼ (r/r s ) n . Hydraulic conductance and diffusive properties are calculated; results are consistent with the concept of a threshold conductance for bone ingrowth. Simple simulations of local flow velocity and local shear stress show no correlation to in vivo bone ingrowth patterns. These results demonstrate a potential for 3D imaging and analysis to define relevant pore scale morphological and physical properties within scaffolds and to provide evidence for correlations between pore scale descriptors, physical properties and bone ingrowth. Crown Copyright Ó 2008 Published by Elsevier Ltd. All rights reserved. 1. Introduction Despite the wide use of porous materials as scaffolds, the design and optimization of scaffolds for successful integration remain an inexact science. Criteria which must be considered in the design of biomaterials include the provision of adequate mechanical strength, the inclusion of adequately large pore volumes to accommodate and deliver a cell mass sufficient for tissue repair, adequate pore interconnectivity with pore sizes large enough to allow continuous tissue growth and sufficient fluid diffusivity, and transport properties to allow for the effective movement of nutri- ents and waste products to and from the implant [1]. While these criteria are important, full analysis of these properties is seldom undertaken. These design criteria are heavily influenced by the pore morphology in scaffolds. To help in the optimal design of scaffolds requires both accurately characterising the scaffold structure in 3D and an ability to characterise the bone regeneration process within the scaffold structure [2–5]. Investigations of bone ingrowth into porous materials with varying pore size have led to the consensus that the optimal pore radius for bone ingrowth is >50 mM and perhaps as large as 150 mM [6,7]. The role of the interconnectivity of pores, the accessibility of pores from the surface of the scaffold, the pres- ence of isolated pores and the importance of measuring these properties in three dimensions have only recently been consid- ered [8,9]. To visualize and determine how pore size/accessibility correlates to mineralised bone content in scaffolds requires partitioning the pore space into discrete pores and investigating the bone ingrowth, connectivity and accessibility at the local scale. The scaffold should also have the correct mechanical properties to match the missing tissue. Interactions between mechanical stimuli, cells and biomaterials have been identified, but the local effects of in vivo mechanical stimuli on cells attached to biomate- rials remain unknown. The amount of mechanical stimulus carried by the scaffold material is dependent upon the scaffold porosity, pore size and shape, and the material properties [10]. * Corresponding author. Tel.: þ61 2 6125 3357; fax: þ61 2 6125 0732. E-mail address: mak110@rsphysse.anu.edu.au (M.A. Knackstedt). Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ – see front matter Crown Copyright Ó 2008 Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.biomaterials.2008.10.056 Biomaterials 30 (2009) 1440–1451