## 1 Introduction  
Various biomedical techniques have been developed to overcome the bone defect. This includes the so-called bone tissue engineering (BTE) method [1]. BTE is a principle of biological discipline and technique to create a temporary matrix. This matrix will be used as a place for bone cells to grow using a scaffold. The scaffold will act as a template for bone cell regeneration, and support the formation of new tissue [2]. Therefore, the scaffold should be biodegradable, biocompatible, and osteoconductive [3]. The scaffold should have a porosity of about 30-90% [4], with minimal pore sizes of 100 \(\upmu\)m to serve as a template for bone cell regeneration and growth [5]. Apart from scaffold, the microenvironment, such as extracellular matrix or the employed cells, also plays an important role in the regenerative processes. Synergism of scaffold and stem cells offers advances and provides biological alternatives for restoring bone defects with improved tissue functions. Currently, researchers are trying to create scaffolds which can enhance the osteogenic differentiation [6]. Stem cells are necessary in the field of translational regenerative medicine. This is owing to the capability of the cells in differentiating into the osteogenic lineage. The differentiation will, in turn, influence the bone treatment. The safety related to in vitro and in vivo models in regenerative medicine is associated with the usage of animal serum. Instead of fetal bovine serum (FBS), human platelet lysate (PL) is now considered. Stem cells cultured in the presence of PL exhibiting a higher healing rate after injury revealed the appropriate option for its clinical-grade use [7]. Polymeric scaffolds are the most popular scaffolds as a model in vitro, and in vivo for bone tissue engineering applications. The selection is made due to ease in altering the physiochemical characteristics. The tunability will support the demands for a comprehensive range of applications in orthopedics. The synthetic scaffold with the predefined properties can be fabricated using nano-hydroxyapatite (n-HA) and chitosan (Ch). This is due to the fact that n-HA is identical to a component of bone [8; 9]. The n-HA are bioactive, biodegradable, and osteeconductive, hence widely utilized as an implant and in bone regeneration applications [10; 11]. The HA has been widely combined with Ch as a composite to form a scaffold. Ch could be formed as porous for bone cell growth, and we can control pore size in the scaffold by merely controlling the compositions of n-HA and Ch [12]. Ch is a natural polymer with excellent biocompatibility and biodegradability. Ch also offers bioresorbable, antibacterial, non-antigenic, biofunctional, and osteeconductive properties. These make Ch suitable for the primary material of composite-based scaffold [12; 13; 14]. To date, various fabrication techniques have been conducted to fabricate the composite-based scaffold. For instance, the freeze-drying method is considered the method of choice. This method is chosen to synthesize the composite-based scaffold, due to simplicity, low cost, and ease of preparation. This method offers an easy way to control the constituent compositions of the composite, including the formation of pores. In this method, the replication of ice crystal dendrites is trapped [15]. Following that, the ice crystal is allowed to evaporate, in order to form pores. In this present research, n-HA/Ch composite-based scaffold is fabricated by the freeze-drying method. The findings reveal lower compressive strength with good cell biocompatibility, compared to a single Ch-based scaffold [16]. The scaffold is required to have good compressive strength at about 2-12 MPa, and, hence, it can be used as a synthetic bone [17]. Herein, we propose embedding a natural polymer carboxymethyl cellulose (CMC) as a composite filler to enhance the mechanical strength of the composite-based scaffold. The CMC has an opposite charge to Ch, therefore, they will create stronger crosslinks via ionic bonds [18; 19].