Targeting biophysical cues to address platelet storage lesions

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.