Attachment and detachment strategies in microcarrier-based cell culture technology: A comprehensive review

Achieving a high cell density of animal cells is a prerequisite for different medical applications such as cell therapy, tissue engineering, and vaccine production. Microcarrier-based cell culture has been proved to be a promising method to attain this purpose mainly due to providing a high surface area to volume ratio. Adhesion and harvesting of cells to and from microcarriers are two critical stages influencing final cell productivity and quality. Low attachment efficiency or non-uniform initial cell distribution onto microcarriers' surfaces lead to the waste of inoculum and achievement of cellular yields less than expected. In other side, inappropriate detachment procedure decreases cell recovery along with having adverse effects on cell viability and behavior. In this review, a comprehensive study on these crucial steps is presented. In the attachment section, cellular mechanisms involved in the attachment process are briefly discussed. Due to the key role of microcarrier surface characteristics in cell attachment and behavior, the chemistry and physical features of various microcarrier surfaces are studied in detail. Then, the influence of seeding conditions on cell attachment is reviewed. In the detachment section, chemical harvesting methods are described initially followed by mechanical detachment. Finally, thermo-responsive microcarriers are discussed in detail. At the end of each section, current challenges and future directions are highlighted.