Controlled-dissolution microcarriers: Engineering rapid on-demand cell harvesting for scalable therapeutic manufacturing

Cell culture technologies have evolved significantly from conventional two-dimensional monolayer systems to advanced three-dimensional (3D) methods. Among various 3D culture tools, microcarriers have emerged as crucial supports for cell adhesion and growth, enabling high-density cell production and overcoming limitations of traditional methods. Microcarriers are tiny spheres widely used in vaccines, tissue engineering, and regenerative medicine. However, cell separation from non-soluble commercial microcarriers remains a critical challenge. This Review examines controlled dissolvable microcarriers as innovative alternatives. These microcarriers can be dissolved after cell proliferation via specific chemical reagents or physical condition changes, facilitating efficient cell harvesting without compromising viability or function. We discuss the key characteristics of ideal microcarriers for harvesting, including biocompatibility, degradability, and controlled solubility. Additionally, we highlight the advantages of controlled dissolvable microcarriers made from materials like gelatin, pectin, and sodium alginate. These microcarriers streamline downstream purification processes, reduce cell loss or damage during separation, and offer safety benefits through non-animal-derived components. This review provides comprehensive insights into the design and application of controlled dissolvable microcarriers, underscoring their potential to enhance efficiency, safety, and reproducibility in cell culture processes for various applications, including cell therapy manufacturing.