Abstract: Cryopreservation of red blood cells is a key technology to ensure the safety of clinical blood and emergency response to public health incidents. Glycerol-based protectants can achieve long-term storage, but their promotion and application in China and emerging (developing) low-income regions are limited due to the complex washing process caused by high osmotic pressure, the low number of red blood cells preserved per unit volume, and relatively serious damage to cell functions. In recent years, the cross-integration of materials science, nanotechnology, and synthetic biology has provided new ideas for the advancement of red blood cell cryopreservation technology: wash-free non-glycerol protectants function through molecular interface engineering (such as trehalose-chitosan nanofiber scaffolds, polyvinylpyrrolidone gradient systems); physicochemical protective nanocomposites (such as mesoporous silica, temperature-responsive hydrogels) have also shown good prospects. This article collates the results of multiple clinical studies and conducts a multi-dimensional comprehensive consideration of the development of cryogenic technology from the three perspectives of technology, economy, and policy. Through innovative formula design, the new wash-free red blood cell protectants not only ensure the cryoprotective effect and the quality of red blood cells after thawing but also completely eliminate or greatly simplify the tedious washing steps after thawing, enabling rapid thawing and immediate use of frozen red blood cells, thus transforming frozen red blood cells from "refrigerator reserves" to "first-aid kit reserves". However, issues such as the biocompatibility and safety of nanomaterials, the lack of an efficient, low-cost, high-throughput protectant screening system, and insufficient energy consumption of freezing equipment under low-temperature conditions remain the biggest obstacles to the breakthrough and clinical promotion of red blood cell preservation technology. In the future, it is necessary to strengthen interdisciplinary collaborative research and development to promote the development of in vitro red blood cell preservation technology towards multi-functional control and low-cost application.

Key words: Frozen red blood cells, Non-glycerol protectants, Trehalose, Interface engineering, Nanocomposites