Staphylococcal protein A-modified hydrogel facilitates in situ immunomodulation by capturing anti-HMGB1 for islet...

Islet transplantation is regarded as the most promising therapy for type 1 diabetes. However, both hypoxia and immune attack impair the grafted islets after transplantation, eventually failing the islet graft. Although many studies showed that biomaterials with nanoscale pores, like hydrogels, could protect islets from immune cells, the pores on biomaterials inhibited vascular endothelial cells (VECs) to creep in, which resulted in poor revascularization. Thus, a hydrogel device that can facilitate in situ immune modulations without the cost of poor revascularization should be put forward. Accordingly, we designed a spA-modified hydrogel capturing anti-HMGB1 mAB (mAB-spA Gel): the Staphylococcus aureus protein A (spA) was conjugated on the network of hydrogel to capture anti-HMGB1mAB which can inactivate immune cells, while the pore sizes of the hydrogel were more than 100μm which allows vascular endothelial cells (VECs) to creep in. In this study, we screened the optimal spA concentration in mAB-spA Gel according to the physical properties and antibody binding capability, then demonstrated that it could facilitate in situ immunomodulation without decreasing the vessel reconstruction in vitro. Further, we transplanted islet graft in vivo and showed that the survival of islets was elongated. In conclusion, mAB-spA Gel provided an alternative islet encapsulation strategy for type 1 diabetes. STATEMENT OF SIGNIFICANCE: Although various studies have shown that the backbone of the hydrogels can isolate islets grafts from immune cells and the survival of the islets can be prolonged by this way, it is also reported that when the pore size of the backbone is too small the revascularization will be adversely affected. According to this point, it is hard to adjust hydrogel's pore size to protect the islets from the immune attack while allowing endothelial vascular cells to creep in. To solve this dilemma, we designed an immunomodulatory hydrogel inhibiting the activation of T cells by immunosuppressive IgGs instead of the backbone network, so the hydrogel can prolong the survival of islets without the sacrifice of revascularization.