Microcarrier culture systems, which were first proposed by van Wezel (1967) in 1967, have gained significant attention in biomedical research for their ability to support cell attachment and growth in three-dimensional (3D) cell culture systems. Unlike conventional methods, microcarriers serve as microscale scaffolds for anchorage-dependent cells enabling increased production capacity (Alkhatib et al., 2017), facilitated process scale-up (Bodiou et al., 2020), reduced cost requirement (Badenes et al., 2016) and improved control in cell culture applications (Chen et al., 2020). Early commercial microcarriers were typically synthetic polymer-based such as poly(lactide-co-glycolide) (PLGA), acrylamide, polystyrene, glass, and silica due to their defined chemical composition and adjustable mechanical properties. However, these petroleum-based commercial microcarriers often exhibit drawbacks such as high production costs, limited biodegradability, and restricted nature of the interaction (Alves et al., 2020; Tavassoli et al., 2018). Additionally, they must be removed from the cell suspension before implantation, leading to the loss of viable cells (Muoio et al., 2021).
In view of such a predicament, there is growing interest in developing microcarriers from biodegradable natural polymeric materials such as collagen (Steffen et al., 2019), gelatine (Nweke and Stegemann, 2022), dextran (Rozwadowska et al., 2016), cellulose (Kalmer et al., 2019), chitosan (Nweke and Stegemann, 2020), alginate (Perteghella et al., 2017)). Among these, cellulose, the most abundant and inexhaustible natural polysaccharide-based biopolymer on Earth, is particularly promising for cellular applications due to its excellent biocompatibility, biodegradability, and good mechanical strength (Courtenay et al., 2018; Seddiqi et al., 2021). Besides that, cellulose can also be chemically modified into various cellulose derivatives to enhance its usefulness in biomedical applications such as wound dressings and tissue engineering (Hon, 2017; Xie et al., 2019). Carboxymethyl cellulose (CMC) is among the cellulose derivatives that have gained remarkable attention. It is produced from the cellulose chain through the substitution of its hydroxyl group backbone with the carboxymethyl group (-CH2-COOH). CMC is a prominent water-soluble polyelectrolyte cellulose biomaterial which is chemically reactive, non-allergenic, non-toxic, and biodegradable (Huang et al., 2017; Kanikireddy et al., 2020; Yusup and Mahzan, 2018). Consequently, CMC is widely used in cosmetics, pharmaceutical products and biomedical applications (Ciolacu and Suflet, 2018; Rahman et al., 2021). However, the primary raw materials for CMC preparation are cotton linter and wood pulp which are considered costly agricultural products, increasing the overall production cost of CMC (Abd El-Sayed et al., 2020). Hence, the interest in the use of agricultural products and by-products as alternative cellulose resources for CMC preparation is gradually increasing.
In view of this, the use of cellulose-rich oil palm empty fruit bunch (OPEFB) presents a useful alternative as a raw material to produce microcarriers. OPEFB is produced in huge quantities in oil palm plantation activities, with 1.07 tons generated per ton of palm oil produced, and the global production of OPEFB in 2018 alone accounted for around 80 million tons (Dolah et al., 2021). Malaysia, as the second-largest palm oil producer and the biggest exporter of oil palm products in the world, generates approximately 15 million tons of OPEFB annually (Abdul et al., 2016). The amount of OPEFB waste is expected to continue to increase due to the abundant land, cheap labour cost, and high global demand for oil palm products (Ali et al., 2020). Since the cellulose content from OPEFB constitutes nearly half its fibre weight, it offers substantial potential as a cellulose source for various applications. Conventionally, OPEFB biomass waste is often burnt or left for the mulching process at the plantation (Faizi et al., 2017). Converting OPEFB into cellulose and CMC could harness its potential as a natural biomaterial source for microcarrier development. While many types of lignocellulosic fibres such as canola straws {Zhang, 2023 #71} and sugarcane bagasse {Lam, 2017 #24} have been used for microcarriers and scaffold fabrication, research on the fabrication of cellulose-based microcarriers from OPEFB is limited, which hinders the exploration of this valuable resource and results in forfeiture of substantial economic value (Idris et al., 2021). Hence, the study believes the use of OPEFB as the cheaper sustainable cellulose resource for the CMC preparation to produce biodegradable microcarrier would be more acceptable.
In this research, OPEFB cellulose is chosen due to the substantial amount of OPEFB biomass waste generated during palm oil production in Malaysia. Therefore, an innovative approach is required to turn OPEFB into a more valuable product that can reduce the negative impact on the environment while increasing the economic use of OPEFB in other non-biodiesel areas in Malaysia. Herein, this study aimed to address this gap by demonstrating the preparation of CMC-microcarriers derived from OPEFB biomass waste through an ionic crosslinking method using an iron (III) chloride solution. The fabricated microcarriers were characterised by physicochemical and morphological properties including particle size, gel content, swelling behaviour, mechanical stability, and in vitro degradation. The findings are expected to advance knowledge in the development of microcarriers from OPEFB, offering a valuable alternative for the application of biodegradable microcarriers in various therapeutic fields.