# Industrial Mass Production of Platelet Dry Powder
## 1 Introduction  
Platelets contain many types of growth factors (GFs): platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), transforming growth factor-beta (TGF\(\beta\)), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), among others [1; 2; 3; 4; 5; 6; 7; 8]. GFs are essential at every stage of physical healing, and consequently, the regenerative properties of platelets have received heightened interest and increased use in various medical fields. Common platelet derivatives include platelet-rich plasma (PRP) [1; 2; 3; 4; 5; 6] and platelet-rich fibrin (PRF) [2; 3; 5]. PRP is prepared by mixing collected blood with a certain amount of anticoagulant and centrifuging the mixture until the blood separates into layers [9; 10; 11]. The uppermost layer is platelet-poor plasma (PPP), and the middle layer is PRP; the bottom layer is predominantly red blood cells. The PRP is then carefully extracted with a syringe to avoid drawing any red blood cells or PPP. PRF is produced from small blood samples and without the addition of any anticoagulants during the preparation process [12; 13]; the blood sample is centrifuged immediately after being drawn and will begin to coagulate during the process, dividing into three layers inside the vial: red blood cells in the bottom layer, plasma-poor platelets in the supernatant, and PRF clots in the middle. PRF clots are rich in fibrin, platelets, and leukocytes. When preparing PRP, to ensure the highest concentration of platelets, the syringe must be carefully welded to avoid the red blood cells and PPP while extracting the PRP layer. Due to this need for precision, PRP preparation is a time-consuming operation, and thetime cost is increased when processing large amounts of blood. Time constraints are an impediment to the mass production of PRP. Because anticoagulants are not used when preparing PRF [12; 13], once collected, blood must be centrifuged immediately before it can congeal. Consequently, PRF preparation cannot be carried out on an industrial or mass scale. In particular, when processing large amounts of blood, a delay in any step may increase the risk of blood coagulation. The inability to mass produce PRP and PRF--due to the complex process of preparing the former and the risk of coagulation in the latter--has limited the range of their applications. The use of PRP and PRF is mainly focused on autologous applications [14; 15; 16]. Nonetheless, due to the constraints associated with human autologous blood, scaling up to mass production presents significant challenges. The inability to produce sufficient amounts means the inability to meet large-scale product demands, as well as the inability to prepare diversified dosage forms tailored to specific applications, limiting the possible commercial applications of platelet dry powder. Within platelets, there are mainly three types of granules: alpha granules, dense granules, and lysosomes [6; 7; 8], each containing different bioactive substances. When platelets are activated by the addition of activators, they release growth factors (GFs) and other bioactive molecules stored in these various granules [5; 17; 18; 19]. During this activation process, the bioactive substances released from the granules initiate a range of biological reactions, including platelet aggregation, cell proliferation, and cell migration. In the preparation of platelet products, activating platelets [14; 20; 21] is essential, and is commonly achieved by adding activators like thrombin, collagen, and calcium chloride solution [17; 22]. Thrombin, often used, is typically derived from bovine sources, posing risks such as high costs and potential immune reactions or allergies in patients [6; 22; 23; 24]. To mitigate these risks, particularly the immunological and transmission concerns related to bovine thrombin, this study utilizes calcium chloride solution as a safer activator alternative.