Therapeutic cell delivery and fate control in hydrogels and hydrogel hybrids

Hydrogels are synthetic or natural polymer networks that closely mimic native extracellular matrices. As hydrogel-based vehicles are being increasingly employed in therapeutic cell delivery, two inherent traits of most common hydrogels, namely low cell affinity and high cell constraint, have significantly drawn the attention of biomedical community. These two properties lead to the unfavourable settlement of anchorage-dependent cells (ADCs) and unsatisfactory cell delivery or tissue formation in hydrogel matrices. Tissue engineers have correspondingly made many efforts involving chemical modification or physical hybridisation to facilitate ADC settlement and promote tissue formation. On the other hand, these two ‘bio-inert’ characteristics have particularly favoured oncological cell therapists, who expect to utilize hydrogels to provide sufficiently high confinement of the delivered cells for anti-cancer purposes. In general, control of cell fate and behaviours in these three-dimensional (3D) microenvironments has become the central aim for hydrogel-mediated cell delivery, towards which various models based on hydrogels and their hybrids have emerged. In this paper, we will first review the development of strategies aiming to overcome the aforementioned two ‘shortcomings’ by (i) establishing ADC survival and (ii) creating space for tissue formation respectively, and then introduce how people take advantage of these ‘disadvantages’ of hydrogel encapsulation for (iii) an enhanced confinement of cell motion.