Multifunctional 4D-printed sperm-hybrid microcarriers for assisted reproduction

Abstract

Remotely controllable microrobots are appealing for various biomedical in vivo applications. In particular, our group has focused in the last years in developing sperm-microcarriers to assist sperm cells with motion deficiencies or low count (two of the most prominent male infertility problems) to reach the oocyte towards in vivo assisted fertilization. Different sperm carriers considering their motion in realistic media and confined environments have been optimized. However, the already reported sperm carriers have been mainly designed to transport single sperm cells, with limited functionality. Thus, to take a step forward, here we propose the development of a 4D-printed multifunctional microcarrier containing soft and smart materials, which can not only transport and deliver multiple sperm cells, but also release heparin and mediate local enzymatic reactions by hyaluronidase-loaded polymersomes (HYAL-Psomes). These multifunctional facets enable in-situ (i) sperm capacitation/hyperactivation, and (ii) local degradation of the cumulus complex that surrounds the oocyte, both to facilitate the sperm-oocyte interaction for the ultimate goal of in vivo assisted fertilization.