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7 CHAPTER 1: INTRODUCTION  12 1. Structure, functions and properties of bone  14 2. Bone fracture healing  17 2.1. The four phases of fracture healing  17 2.2. Pathology of fracture healing  20 2.3. Response of bone fracture to mechanical stimulation 21 3. Angiogenesis  22 3.1. Mechanisms of angiogenesis  23 3.2. Regulation of angiogenesis  26 3.3. In vitro models of angiogenesis  29 4. Mesenchymal stem cells  30 4.1. Drug delivery  31 5. Aims of the study 33 CHAPTER 2: MATERIALS AND METHODS  34 1. Materials  36 2. Methods  40 2.1. Haematomas  40 2.2. Cell culture  42 2.3. Tube formation assays  44 2.4. Proliferation of MSCs  46 2.5. Migration assays  46 2.6. Differentiation assays of MSCs  47 2.7. Quantification of proteins  50

Paracrine stimulation of endothelial cells and mesenchymal stem cells by the mechanically loaded human fracture haematoma