(391e) Oxime Crosslinked Alginate Hydrogels with Tunable Stress Relaxation for Immune CELL Encapsulation

Sodium alginate hydrogels have served as a versatile and reliable tool for biomedical applications such as 3-D cell encapsulation, both in vitro and in vivo. In the past, these hydrogels have formed via ionic or covalent crosslinking of the alginate chains upon the modification of its functional groups. Hereby, we employ a technique to modify hydroxyl groups of the alginate backbone to alkoxyamine groups (-O-NH₂), and we verify such modifications in 1D and 2D NMR. Alkoxyamine groups pertain to the field of click bioorthogonal polymer crosslinking. In the presence of aldehyde-containing oxidized alginate chains, both polymers can form oxime reversible covalent crosslinks, whose formation thermodynamics have been proved to be responsive to environmental variables such as pH and temperature. Upon hydrogel formation in physiologically relevant aqueous media (pH 7.4, 37ºC), gels of a wide variety of stiffnesses (storage moduli of G’ = 80 Pa - 12 kPa) and viscoelasticity (mean stress relaxation times 〈τ〉 = 4.2 h – 56.2 h) can be achieved. These properties are tailored by controlling the previously mentioned environmental variables, the ratio between alkoxyamine and aldehyde groups, and the degree of functionalization of the oxidized alginate counterpart. Furthermore, the control of design parameters inherent to the gel formation, such as the gelation time, can be utilized in order to form gels of different geometries. We employ an electrojetting assembly with which we can generate hydrogel microbeads with electrospraying; or hydrogel microthreads with electrically driven extrusion; all with a diverse set of viscoelastic properties. Last, we will discuss the employment of such hydrogel formulations in order to study the influence of stress relaxation on the proliferation capability of immune cells.