Temperature-modulated separation of therapeutic cells, viral vectors, and exosomes using functional polymers

Abstract

In recent decades, advanced therapeutic modalities such as therapeutic cells, viral vectors, and extracellular vesicles (exosomes), have emerged as effective therapies for intractable diseases. These therapeutic modalities produced through bioprocesses must be purified from contaminants. Effective separation methods are essential for optimizing therapeutic modalities. This review highlights innovative temperature-modulated separation methods enabled by the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm). The design of PNIPAAm-modified interfaces plays a pivotal role in ensuring precise and efficient separation. We summarize the recent advancements in the application of temperature-modulated separation methods for cells, viral vectors, and exosomes, with a focus on the design of PNIPAAm interfaces.

Keywords: Biomaterials; Polymer brush; Regenerative medicine; Temperature-responsive chromatography; Thermoresponsive interface; Thermoresponsive polymer.

Fig. 1

Illustration of A temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and B PNIPAAm brush-modified interfaces

Fig. 2

Temperature-modulated cell separation using thermoresponsive ionic polymer brushes. A UCMSC separation using a thermoresponsive cationic block copolymer brush-grafted glass substrate B BMMSC separation from differentiated adipocytes using a mixed polymer brush composed of PNIPAAm- and PDMAPAAm-modified glass substrates

Fig. 3

Temperature-modulated cell separation using thermoresponsive affinity polymer brushes. A Vascular cell separation using peptide-conjugated thermoresponsive block copolymer brush-grafted glass substrate and B hepatocyte separation using thermoresponsive glycopolymer block copolymer brush-grafted glass substrate

Fig. 4

Temperature-modulated cell separation column. A Illustration of the cell separation column using thermoresponsive cationic block copolymer brush-grafted beads and B cell composition at each fraction

Fig. 5

Temperature-modulated viral vector purification. A Illustration of packing materials for the purification column and B purification procedure and virus elution at two temperatures

Fig. 6

Temperature-modulated capture of exosomes using a thermoresponsive block copolymer brush with affinity peptides