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The emergence of regenerative medicine has resulted in a novel interdisciplinary field that focuses on repair, replacement, and regeneration of diseased or damaged tissues or organs. As one of the most important strategies in regenerative medicine, the field of tissue engineering (which typically combines biodegradable scaffolds, (stem) cells, and bioactive signals such as growth factors) has created new possibilities to produce implantable tissues ex vivo. This chapter focuses on the most recent advances in research on micro- and nanospheres aiming at improvement of the functionality and clinical efficacy of traditional scaffolds for soft and hard tissue engineering. Depending on their origin, polymeric micro- and nanospheres can be classified as either natural or synthetic polymers, both of which have their specific pros and cons.