3D imaging of tissue integration with porous biomaterials

Abstract

Porous biomaterials designed to support cellular infiltration and tissue formation play a critical role in implant fixation and engineered tissue repair. The purpose of this Leading Opinion Paper is to advocate the use of high resolution 3D imaging techniques as a tool to quantify extracellular matrix formation and vascular ingrowth within porous biomaterials and objectively compare different strategies for functional tissue regeneration. An initial over-reliance on qualitative evaluation methods may have contributed to the false perception that developing effective tissue engineering technologies would be relatively straightforward. Moreover, the lack of comparative studies with quantitative metrics in challenging pre-clinical models has made it difficult to determine which of the many available strategies to invest in or use clinically for companies and clinicians, respectively. This paper will specifically illustrate the use of microcomputed tomography (micro-CT) imaging with and without contrast agents to nondestructively quantify the formation of bone, cartilage, and vasculature within porous biomaterials.

Three-Dimensional Characterization of Tissue-Engineered Constructs by Contrast-Enhanced Nanofocus Computed Tomography

“…According to specific study objectives, a customized strategy will be required to extract the necessary information in a robust way, ranging from (1) accurate and detailed (100s of mm scale) identification and quantification of different TE construct components limited to small TE construct samples and using phase-contrast imaging, 25 to (2) using standard desktop micro-or nano-CT as a routine 3D imaging technique for whole TE construct analysis (mm to cm scale) and quantification of mineralization after in vivo implantation. 10,13 The latter approach, without the use of a contrast agent, has also been used for static or bioreactor in vitro cultures, 16,18,19 showing distinct contrast differences between the mineralized matrix and scaffold. Phase-contrast imaging [24][25][26] or micro-CT combined with osmium tetroxide as a contrast agent 28 has shown its potential to assess nonmineralized ECM in an in vitro engineered TE construct.…”

“…In particular, Xray microfocus computed tomography (micro-CT) has been frequently applied as a 3D quantitative imaging technique to assess the scaffold structure, [6][7][8] as well as bone ingrowth after in vivo implantation. 6,[9][10][11][12][13][14] Furthermore, it has been employed for time-lapsed follow-up of mineralization inside scaffolds during in vitro static [15][16][17] or bioreactor cultures. 13,18,19 In most of these studies, polymeric, ceramic, collagen scaffolds, or composites were used, in which, the mineralized extracellular matrix (ECM) could be separated from the scaffold for the purpose of volume calculations and no significant material-dependent artifacts were present.…”

“…6,[9][10][11][12][13][14] Furthermore, it has been employed for time-lapsed follow-up of mineralization inside scaffolds during in vitro static [15][16][17] or bioreactor cultures. 13,18,19 In most of these studies, polymeric, ceramic, collagen scaffolds, or composites were used, in which, the mineralized extracellular matrix (ECM) could be separated from the scaffold for the purpose of volume calculations and no significant material-dependent artifacts were present. However, when imaging the ECM or tissue growth in metallic scaffolds or around implants, additional caution has to be taken during image analysis as metal artifacts 20,21 can significantly influence the accuracy of the quantification of the newly formed ECM or tissue volume.…”

Effect of surface roughness on osteogenesis in vitro and osseointegration in vivo of carbon fiber-reinforced polyetheretherketone–nanohydroxyapatite composite

“…32,33 These results suggest that only appropriate surface roughness could greatly promote the biological activity of the implants.…”

Aortic Arch Morphogenesis and Flow Modeling in the Chick Embryo

“…Quantitative 3D imaging using micro-CT has become a standard technique for quantitative 3D reconstruction of complex micro-morphologies including bone [19], vasculature [20] and recently, the developing heart [21]. The initial objective of this research is to establish and validate a multi-modal quantitative approach to investigate and quantify normal (healthy)…”