ROS-scavenging microgels containing PTPσ receptor modulatory peptides synergistically alleviate inflammation and promote functional recovery post stroke

The glial scar forms a disadvantageous microenvironment for neurogenesis after stroke. Single treatment targeting glial scar suppression or neurogenesis promotion is insufficient for stroke repair. To improve the functional recovery post stroke, a synergistical therapy of reactive oxygen species (ROS)-scavenging polymers (hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol, HBPAK) and chondroitin sulfate proteoglycans (CSPGs) receptor (protein tyrosine phosphatase σ, PTPσ) modulatory peptides (intracellular sigma peptide, ISP) was applied in a form of microgels for inflammation alleviation, glial scar inhibition and endogenous neuroblasts regulation. The microgels were prepared with a microfluidic device under UV irradiation. The microgels containing HBAPK displayed efficient elimination of typical ROS of 1-diphenyl-2-picryl hydrazyl radical (DPPH) and H2O2. The microgels containing HBAPK and ISP peptides decreased inflammation response of lipopolysaccharide (LPS) activated BV2 microglia. Promoted cell migration and proliferation of Schwann cells (SCs) and strengthened cell stemness and neuronal differentiation of neural stem cells (NSCs) were shown when these cells were incubated within the microgels containing HBAPK and ISP peptides. Injection of the microgels in vivo achieved positive therapeutic effects with respect to motor dysfunction recovery promotion, inflammation alleviation and cell apoptosis reduction at 7 d, and astrocytic scar inhibition, neuroblasts promotion and axonal neurofilaments increase at 28 d post stroke, suggesting the effectiveness of this synergistical therapy for stroke.