Nanouterus.like: commercial implementation of a 3d culture system to improve in vitro embryo production

• Grant number: 22/06068-5
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: November 01, 2022
• End date: November 30, 2023
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Raquel Zaneti Puelker
• Grantee: Raquel Zaneti Puelker
• Company: BLASTOCELL BIOTECHNOLOGIES LTDA
• CNAE: Criação de bovinos ; Atividades de atenção à saúde humana não especificadas anteriormente
• City: Presidente Prudente
• Pesquisadores principais: Anthony César de Souza Castilho
• Associated researchers: Sarah Gomes Nunes
• Associated research grant(s): 24/18064-0 - NanoUterus.Like: the new era of 3D embryo culture for improving animal reproductive efficiency, AP.PIPE

Abstract

Despite the commercial success of in vitro embryo production (IVP), current conditions available in human medicine and the animal production industry are still below ideal. In fact, the loss of in vitro development of bovine oocytes to the blastocyst stage is near 60 to 70%. In this context, improvements to expand productivity and quality can be research and development (R&D), to increase even more the economic impact (since the field movement more than BRL 597 billion in 2018, only in the beef sector) of this biotechnics and its bioprocess improvement. This scenario of low production can be related, in part, to the IVP system happening in a two-dimensional (2D) environment. Although the three-dimensional (3D) system has gained attention in recent years, little progress in animals as human medicine has been made. In addition, there is still a low reproducibility and little validation of effective evidence in their studies. Thus, an in vitro 3D maturation (IVM-3D) is a promising approach to improving oocyte maturation, as it reduces the flattening of the cumulus-oocyte complex (COCs) and preserves its structural and functional integrity. Initially, to ensure maturity and oocitary capacity; furthermore an innovative technology in the market, our group implements the proposal of a IVM-3D system, the NanoUterus.Like, as using the CellFate® 3D Matrix, in partnership with Biocelltis Biotecnologia S.A, Florianópolis, Brazil. It is important to highlight that despite using the model for initial tests on different species, our system covers the expansion with greater commercial and sanitary appeal: cattle, horses, porcine, and sheep; focusing in particular on the human species, by using the bovine as an ideal and most representative biological model. For this, COC's cattle will be aspirated from the ovary through the Ovum Pick Up (OPU) and matured in vitro using the new NanoUterus.Like system. After 24 hours, part of the matured COCs will be vitrified and the others will be chosen from cell and molecular evaluations of oocyte competence acquisition to fertilization and embryo production: meiotic progression, mitochondrial membrane potential, stress and apoptosis evaluation. Subsequently, part of the COCs will move on to fertilization and embryonic in vitro culture. At the end, this evaluation of the production and vitrification rate will be used, as indicators to prove the use and update of the IVM with the commercial use of NanoUterus.Like system. In summary, our technology will allow COCs to be matured in the 3D dimension, promoting significant differences in cellular competence and behavior, we expect that our system improvements in differentiation, proliferation and quality processes in compared to the 2D system. In addition, the 3D CellFate® Matrix will also be able to offer a drug-delivery system allowing, in the future, the controlled release of substances and components that benefit the IVM of mammalian oocytes. Finally, we hope that will be an ideal commercial model for the evaluation of new products and bioprocesses that can maximize the fertility of mammalian species in assisted reproduction programs. (AU)