The skeletal system comprises multiple tissues which converge in the formation of complex biological structures such as hierarchical bone, organized cartilage, joints, and tissue interfaces. However, different human conditions derived from aging, lifestyle, illness, or trauma can damage the components of the human skeletal system and lead to loss of function and reduced life quality. In the context of skeletal tissue engineering, physical and biological demands play a key role in the successful construction and implantation in bone, cartilage, and blood vessel tissue formation. After a brief summary of the biological properties of supportive connective tissues, namely bone and cartilage, the chapter is organized in three different technological sections: (i). grafting-based tissue engineering techniques, (ii). 3D bioprinting technology, and (iii). in vitro organ modeling based on organ-on-a-chip. With scientific progress and emergence of different in vitro models, knowledge of the entire organism behavior is growing, but the possibility to mimic the complexity of human skeletal tissues and their functionality is still a significant ongoing challenge.
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