InVitro Models for Drug Discovery and Toxicity Testing

Philip Lazarovici, Mengyan Li, Anat Perets, MarkJ. Mondrinos, Shimon Lecht, Christopher D. Koharski, Paul R. Bidez III, Christine M. Finck, and Peter I. Lelkes

1.1 Introduction 3

1.2 Intelligent Biomaterials and Scaffolds for Tissue Engineering 4

1.2.1 Synthetic Materials 4

1.2.2 Natural Biomaterials 5

1.3 Fabrication of Scaffolds for Tissue Engineering 7

1.3.1 Electrospinning 7

1.3.2 Controlled Lyophilization 9

1.3.3 Acellularization 10

1.4 Progress and Achievements in Liver Tissue Engineering 11

1.4.1 The Liver 11

1.4.2 Scaffolds for Liver Tissue Engineering 12

1.4.3 Pharmaceutical Applications of Tissue-Engineered Liver Models 15

1.4.4 Conclusions and Novel Trends in Liver Tissue Engineering 16

1.5 Cardiac Tissue Engineering: Cells and Models 16

1.5.1 Cardiac Tissue Engineering 16

1.5.2 Cells used in Cardiac Tissue Engineering 17

1.5.3 Culture Models of Cardiac Tissue-Engineered Constructs 18

1.5.4 Specific Scaffolds Developed for Cardiac Tissue Engineering 20

1.6 In-Vitro-Engineered Pulmonary Tissue Models: Progress and Challenges 21

1.6.1 Lung Tissue Engineering: The Current State of Play 21

1.6.2 Existing In-Vitro Pulmonary Cell and Tissue Culture Biological Models 26

1.6.3 Potential of Alveolar Tissue Models as Disease Models in Pharmaceutical Sciences 27

1.6.4 The Future: Toward Engineered 3D Alveolar Tissue for Cell Therapy and Pharmacological Models 27

1.7 In-Vitro Models of the Blood-Brain Barrier (BBB) 28

1.7.1 The BBB, a Neurovascular Physiological Unit: The Concept 28

1.7.2 In-Vitro BBB Models: Cells and Devices 32

1.7.3 BBB In-Vitro Models: From First to Third Generation; the Biological Approach 35

1.7.4 Trends in Tissue Engineering: Realistic In-Vitro BBB Pharmacological Models 36

1.7.5 Conclusions for BBB In-Vitro Models 38 References 39

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