Hydrogel microparticles (HMPs) have been widely investigated for tissue engineering and drug delivery due to their resemblance to native tissue and ease of biofunctionalization. However, translation of these highly tunable systems has been hindered by covalent crosslinking methods. While often employed (meth)acrylate moieties afford spatial-temporal control of crosslinking and functionalization, the strong C-C bonds formed prevent degradation/resorption and ultra-violet curing methods challenge efficient cellular encapsulation. Stereocomplexation, a stereospecific form of physical crosslinking, provides a strong yet degradable alternative for creating translationally relevant HMPs. For this system, gel network components consisting of 4-arm polyethylene glycol (PEG) stars with poly(L-lactic acid) (PLLA) oligomeric chain ends and propargyl-containing ABA crosslinkers with enantiomeric poly(D-lactic acid) (PDLA) chain ends were synthesized. Droplets of these gel precursors in ethyl acetate were formed via a microfluidic organic-in-oil system where HMPs self-assemble via stereocomplexation after precipitation in deionized water. By varying the flow rate of the dispersed phase, control of HMP size was demonstrated with diameters of 33.7 ±8.4, 62.4 ± 9.2, and 105.7 ± 12.8 µm. Gelation due to stereocomplexation was confirmed via wide angle x-ray scattering (WAXS) in which lyophilized HMPs exhibited the known signature diffraction pattern of stereocomplexed PLA at 2θ = 11.9, 20.6, 23.6°. Differential scanning calorimetry (DSC) also confirmed stereocomplexation within the HMPs by the appearance of an exotherm (T_c= 37°C) and a high temperature endotherm (T_m = 159°C) that do not appear in the hydrogel precursors alone. Additionally, the propargyl handle located on the crosslinker allows for thiol-yne “click” functionalization as demonstrated by a post-fabrication addition of FITC-PEG-SH to the HMPs. Thus, this HMP scaffold provides a controlled, functionalizable, fully degradable system with potential for biofunctionalization, mechanical/degradable tunability, and formation of microporous annealed scaffolds showing great promise for future use in regenerative medicine technologies.

Stereocomplexed hydrogel microparticles via microfluidic assembly

Gianna Tutoni

Appearances