## 1 Introduction  
Calcium sulfate/calcium phosphate (CS-CP) composites are commonly used as bone substitute materials in clinical applications such as symptomatic osteonecrosis of the femoral head, bone tumors, critical size bone defects, spine and dental surgery, hemostatic agent in orthodontic treatment, and increased angiogenesis [1, 2, 3, 4, 5]. CS-CP combines the advantages of the two materials with the properties of biocompatibility, osteo-conduction, and osteo-integration [6, 7, 8]. CS-CP is available in different forms, such as granules, injectable kits, and premixed putties [9, 10, 11, 12]. Compared with other forms, premixed putty is simpler to use and is cohesive and moldable. Moreover, it does not require intraoperative mixing, nor is restricted by defect forms [10]. There is a higher risk of infection in the mixing process of preparing the injectable kits [13]; moreover, different brands of bone substitutes use various different mixing methods, rules, and surgical instruments, making their use more complicated. Moreover, some critical issues arise. For example, it is difficult to completely stop the bleeding during an operation because bone substitutes can come into contact with blood or body fluids that can change the anti-washout properties of the premixed putties [14] and disintegrate the implant [15, 16]. Washed particles can cause slight inflammation and severe foreign-body responses [15]. The inflammation reaction depends on the size, morphology, and concentration of the particles determined predominantly by the washout rate. It has been shown that particles smaller than 10 \(\upmu\)m and concentrationsmore than 0.1% reduced osteoblast viability and proliferation activity [17]. Compared with spherical-shaped or irregular particles, needle-shaped particles generate a prolonged inflammatory response in macrophages [18]. Macrophages are directly internalized and can digest small particles (<10 \(\upmu\)m). In addition, they secret inflammatory cytokines (IL-1, IL-6, MCP-1, and TNF-\(\upalpha\)) to produce an inflammatory response [19]. In addition, the implantation of commercial CS-CP in premixed putty produces an inflammatory response, and particles were found in the inflammatory area in case reports and clinical trials [14; 15].  
Therefore, anti-washout properties are important in the clinic to prevent disintegration. Anti-washout property can be improved by cohesion promoters such as sodium alginate [16], chitosan [18], sodium polyacrylate [19], collagen [20], hyaluronic acid [21], hydroxypropyl methylcellulose (HPMC) [22], gelatin [23], carrageenanan [24], and thermosensitive hydrogel [25].  
HPMC and glycerin are used as plasticizers in injectable or putty forms in commercially available bone substitutes [26; 27; 28; 29]. Because of its biocompatibility [30], degradability [31], and non-toxic properties, HPMC has been used as a scaffold material in bone tissue engineering [32; 33]. In addition, HPMC increases osteogenesis [34; 35] and does not affect the degradation time [36]. GLY greatly improves injectable and increases the setting time [27; 37]. Apart from this, it can be stored at room temperature without drying out and has been frequently used in clinical applications [28; 29]. Although research on using plasticizers to improve cohesion in bone substitute materials has been quite extensive, two different plasticizers, which are washed particles, produced by plasticizers, have not been fully explored.  
In this work, we evaluated CS-CP in premixed putty using a HPMC and glycerol carrier, and the anti-wash out properties of CS-CP powder loaded in HPMC at various ratios were characterized by microstructure analysis and particle morphology.