Emerging nanoparticle-based cryoprotectant delivery systems in vitrification: Implications for toxicity reduction, devitrification control, and sperm deoxyribonucleic acid fragmentation

Abstract:

Cryopreservation is a vital component of modern biomedical practice, spanning regenerative medicine, fertility preservation, organ transplantation, and biobanking. However, traditional cryopreservation procedures such as slow freezing and vitrification are associated with several challenges. In male infertility, sperm deoxyribonucleic acid fragmentation (SDF) is a crucial factor influencing reproductive outcomes. Growing evidence suggests that cryopreservation intensifies oxidative stress-induced genomic damage, resulting in compromised fertilization, suboptimal embryo development, and implantation failure. These limitations have been particularly prominent in the case of complex three-dimensional organoids and tissue-engineered scaffolds. The review aims to critically evaluate the current state of nanoparticle-assisted cryoprotectant delivery to improve vitrification efficiency. A structured review of the existing literature was conducted to evaluate the roles of lipid-based, polymeric, and inorganic nanoparticles in cryopreservation. There is significant focus on SDF and the processes that cause it, such as the generation of reactive oxygen species, breakdown of membrane lipids, and chromatin instability during freeze–thaw cycles. The mechanistic role of these nanoparticles in improving vitrification efficiency has been clearly understood. The use of lipid nanoparticles has shown potential in improving intracellular cryoprotectant agent (CPA) delivery and reducing CPA concentration gradients. The use of polymeric nanoparticles, such as poly(lactic-co-glycolic acid) and chitosan (CS), has shown potential in the controlled and sustained delivery of CPAs. The use of inorganic nanoparticles, including superparamagnetic iron oxide, mesoporous silica, and gold nanoparticles, has shown potential in improving vitrification efficiency. The use of antioxidants has shown potential in improving cellular resilience. The use of nanoparticles has shown potential in improving the therapeutic index of vitrification.