Preclinical alternative model for analysis of porous scaffold biocompatibility in bone tissue engineering

Abstract

Angiogenesis is the physiological process of forming new capillaries from existing vessels. It is a tiered process involving activation of the existing endothelial cells, degradation of the extracellular matrix, proliferation and migration of endothelial cells, invasion of the stroma by the surrounding cells, and remodeling the extracellular matrix. Regulation of endothelial cell survival and migration strongly depends on the interaction of endothelial cells with extracellular matrix proteins via cell adhesion molecules, and the activities of growth factors and cytokines. Angiogenesis is characteristic of regeneration of normal tissues and hence is an important factor determining the safe and successful use of biomaterials in regenerative medicine (Chavakis and Dimmeler, 2002) as perfusion of the implant is needed to provide a feasible infrastructure upon which the new tissue can mature (Anderson et al., 2011). Induction of angiogenesis and subsequent development of a vascular bed in the engineered tissue is being actively pursued through combinations of physical and chemical cues, notably through the presentation of suitable topographies and growth factors (Klagsburn and Moses, 1999;Liu et al., 2012;Kant and Coulombe, 2018).

Evolving applications of the egg: chorioallantoic membrane assay andex vivoorganotypic culture of materials for bone tissue engineering

“…35,38,39 Given that the size, stiffness, roughness and porosity of materials and the different types of cells/ growth factors incorporated within a scaffold can affect cell attachment, differentiation and survival, the CAM allows these variables to be tested economically and quickly, potentially preventing the use of rodent models in the first instance. 35,40…”

“…The CAM is made of three layers – the endoderm, ectoderm and mesoderm. 40 Fixation of the scaffolds in situ limits bleeding from small vessels when removed from the CAM. 72 Critically, inflammatory angiogenesis must be distinguished from an angiogenic response due to the material analysed at later time points, by histology and immunohistochemistry 40 as monocytes and inflammatory-like cells are active in the CAM.…”

“… 40 Fixation of the scaffolds in situ limits bleeding from small vessels when removed from the CAM. 72 Critically, inflammatory angiogenesis must be distinguished from an angiogenic response due to the material analysed at later time points, by histology and immunohistochemistry 40 as monocytes and inflammatory-like cells are active in the CAM. 138 Bai et al 92 looked at interleukin-10, interleukin-12 and nitric oxide release to determine macrophage activation in response to their growth factor releasing scaffolds.…”

Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products

“…The relevancy of either scenario to final human use is questionable. For this reason, there is growing interest in humanised in vitro or ex vivo models [129][130][131].…”

Depletion of Embryonic Macrophages Leads to a Reduction in Angiogenesis in the Ex Ovo Chick Chorioallantoic Membrane Assay

“…In vivo models, such as mice models, are biologically more relevant but come at a higher cost, and real-time imaging as well as manipulations in these models are relatively complex [ 5 ]. Besides the technical and practical problems in many in vivo models, ethical issues remain a point of discussion when laboratory animals are involved [ 6 ].…”