Angiogenesis Assays for the Evaluation of Angiogenic Properties of Orthopaedic Biomaterials - A General Review

Vascularization is an essential process in bone formation, remodeling and regeneration during both bone development and fracture repair. Vascularization remains a big challenge directly leading to the final success of newly regenerated bone. In this review, the advantages and disadvantages of different angiogenesis assays and bone defect models are described in details for investigating revascularization of materials of interest. Unlike conventional angiogenesis study with growth factors or pharmaceutical molecules performed in two-dimension, special considerations are taken into account whether these assays can be translated for testing three-dimensional implantable devices. Over the years, accurate and quantifiable in vitro, ex vivo and in vivo assays have been extensively demonstrated to be useful in examining how new blood vessels grow. These methods can contribute to the fundamental understanding of angiogenic properties of the materials, but a bone defect model is still pivotal in order to understand the cascade actions of angiogenesis along with bone formation. Finally, angiogenesis and osteogenesis are both complex processes interacting with each other, the choice of which assay to be performed should adequately address the clinical relevance and reflect the sequence of responses of revascularization of the test materials.