Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

Abstract

Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs.

In vitro and in vivo studies of a novel bacterial cellulose-based acellular bilayer nanocomposite scaffold for the repair of osteochondral defects

“…µCT scanning is a relatively new approach in the bone-engineering field where the technique can be utilized to calculate the BV based on real 3D spatial distribution. 46 In the present study, this technique complemented well with the histological assessment. The subchondral bone formation may have resulted from osteoconductive property of nanocomposite BC-HA activated with BMP-2.…”

A Mechanobiological Model for Tissue Differentiation that Includes Angiogenesis: A Lattice-Based Modeling Approach

“…It describes the overall dentritic structure and pattern of the capillary network similar to those observed in vivo (see for example, Lu et al 41 ). The experimental quantification of newly formed microvessels constitutes an active field of research 45,63 and not many quantitative studies have looked at angiogenesis during a bone regeneration process. Microvascular networks are difficult to quantify due to their small size, location, and complex 3D structure.…”

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)…”