Wang Shichun, Liu Qi, Cheng Lihan, Wang Lu, Xu Feng, Yao Chunyan
Department of Blood Transfusion, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, PR China.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China; Bioinspired Engineering and Biomechanics Center (BEBC), Xi'an Jiaotong University, Xi'an, 710049, PR China.
Acta Biomater. 2022 Oct 1;151:118-133. doi: 10.1016/j.actbio.2022.08.039. Epub 2022 Aug 23.
Platelets play vital roles in vascular repair, especially in primary hemostasis, and have been widely used in transfusion to prevent bleeding or manage active bleeding. Recently, platelets have been used in tissue repair (e.g., bone, skin, and dental alveolar tissue) and cell engineering as drug delivery carriers. However, the biomedical applications of platelets have been associated with platelet storage lesions (PSLs), resulting in poor clinical outcomes with reduced recovery, survival, and hemostatic function after transfusion. Accumulating evidence has shown that biophysical cues play important roles in platelet lesions, such as granule secretion caused by shear stress, adhesion affected by substrate stiffness, and apoptosis caused by low temperature. This review summarizes four major biophysical cues (i.e., shear stress, substrate stiffness, hydrostatic pressure, and thermal microenvironment) involved in the platelet preparation and storage processes, and discusses how they may synergistically induce PSLs such as platelet shape change, activation, apoptosis and clearance. We also review emerging methods for studying these biophysical cues in vitro and existing strategies targeting biophysical cues for mitigating PSLs. We conclude with a perspective on the future direction of biophysics-based strategies for inhibiting PSLs. STATEMENT OF SIGNIFICANCE: Platelet storage lesions (PSLs) involve a series of structural and functional changes. It has long been accepted that PSLs are initiated by biochemical cues. Our manuscript is the first to propose four major biophysical cues (shear stress, substrate stiffness, hydrostatic pressure, and thermal microenvironment) that platelets experience in each operation step during platelet preparation and storage processes in vitro, which may synergistically contribute to PSLs. We first clarify these biophysical cues and how they induce PSLs. Strategies targeting each biophysical cue to improve PSLs are also summarized. Our review is designed to draw the attention from a broad range of audience, including clinical doctors, biologists, physical scientists, engineers and materials scientists, and immunologist, who study on platelets physiology and pathology.
血小板在血管修复中发挥着至关重要的作用，尤其是在初级止血过程中，并且已广泛应用于输血以预防出血或处理活动性出血。近年来，血小板已被用于组织修复（如骨骼、皮肤和牙槽组织）以及细胞工程中作为药物递送载体。然而，血小板的生物医学应用与血小板储存损伤（PSLs）有关，导致输血后恢复、存活和止血功能降低，临床结果不佳。越来越多的证据表明，生物物理线索在血小板损伤中起重要作用，例如剪切应力引起的颗粒分泌、底物硬度影响的黏附以及低温引起的细胞凋亡。本综述总结了血小板制备和储存过程中涉及的四种主要生物物理线索（即剪切应力、底物硬度、静水压力和热微环境），并讨论了它们如何协同诱导PSLs，如血小板形状改变、激活、凋亡和清除。我们还综述了体外研究这些生物物理线索的新兴方法以及针对生物物理线索减轻PSLs的现有策略。我们最后展望了基于生物物理学的抑制PSLs策略的未来方向。重要性声明：血小板储存损伤（PSLs）涉及一系列结构和功能变化。长期以来人们一直认为PSLs是由生化线索引发的。我们的手稿首次提出了血小板在体外制备和储存过程的每个操作步骤中所经历的四种主要生物物理线索（剪切应力、底物硬度、静水压力和热微环境），它们可能协同导致PSLs。我们首先阐明这些生物物理线索以及它们如何诱导PSLs。还总结了针对每种生物物理线索改善PSLs的策略。我们的综述旨在引起广泛读者的关注，包括研究血小板生理学和病理学的临床医生、生物学家、物理科学家、工程师、材料科学家和免疫学家。
