人体生物矿化与病态结晶研究进展

In the chemical industry, crystallization is an indispensable unit operation in the separation of the solid-liquid phase and a ubiquitous method to manufacture high-value crystal products. In nature, crystallization resulting in mineralization is a more general phenomenon in organisms. Modern crystallization technology is gradually expanding into the field of biomolecular engineering. However, biomineralization, in which organisms form tissues with biological functions by controlling the precipitation and crystallization of inorganic nanocrystals in organic matrices, is a dynamic, complex process that accompanies the organism throughout its life. But, when abnormal fluctuations occur in the body’s internal chemical environment, pathological mineralization occurs, resulting in the precipitation of inorganic or organic salt crystals which are aberrant crystallizations, a process known as pathological crystallization, causing disease and endangering human health, such as kidney stones, gall stones, malaria, and gout. Compared to the conventional crystallization from solution in chemical engineering which contains crystal nucleation, growth, and aggregation, biomineralization involves many microscopic and macroscopic processes such as ion/molecular assembly into nuclei, crystal-liquid interface mass transfer, and particle aggregation, which strongly couples with the physiological environment. The limitation of conventional crystallization hinders the advancement in understanding the mechanism of the ion/molecular crystallization process and the regulation of complex environments in vivo, resulting in the blindness of the screening and development of drugs for the treatment and prevention of such diseases. The study of biomineralization is a frontier research field and their discoveries in pathological crystallization are supposed to promote the development of clinical medicine. Based on the latest research in crystal engineering and crystallography, we take the common pathological mineralization-induced diseases (malaria, kidney stones, atherosclerosis, gall stones, gout) as examples, and select recent representative and significant findings from the perspective of understanding the mechanism of the crystallization process. The mechanisms of inorganic and organic crystal crystallization processes related to these diseases are reviewed, focusing on the molecular mechanisms of crystal nucleation, growth, agglomeration, and adhesion at diverse scales during different stages of the disease. The mechanisms of the crystallization inhibitors (molecules that inhibit the nucleation, growth, aggregation, or agglomeration process of pathological crystal) are also reviewed. The aim of the research on the crystallization and inhibition mechanisms is to build up guidelines for the screening and designing of effective inhibitors. Based on these findings, researchers have successfully designed many potent molecules that hold promise as a novel therapeutic modality. At the end of the review, the key research challenges and future directions in pathological mineralization are given. To meet the practical needs of clinical drug development, pathological mineralization researchers still face many challenges in understanding the mechanism of the crystallization process, screening drugs, establishing platforms and models, and building guidelines for medical advancement. Due to the complex environments in vivo, it is difficult to understand the mechanism of crystallization under the interaction between multiple ions/molecules and drugs, where molecular recognition plays important role in specific binding to crystal surface sites. The research on crystallization mechanism aims to screen potential pathological crystal inhibitors. Because considerable studies are based on in vitro experiments, more attention should be paid to the building platforms and models that can mimic human environments and use molecular design tools to selectively inhibit the crystallization process, which is believed to be the most potent strategy to find the specific drug for the biomineralization-induced disease. Finally, it is necessary to establish scientific and efficient guidelines for medicine development and provide effective therapeutic and preventive measures for biomineralization-induced diseases.