An investigation of scavenger receptor A mediated leukocyte binding to polyanionic and uncharged polymer hydrogels

Cell adhesion to biomaterials can be mediated in part by mechanisms aside from the traditionally recognized opsinization and integrin binding mechanisms. In this study, we investigated the role of scavenger receptor A (SR-A) in leukocyte binding to a series of well-controlled polyanionic and uncharged hydrogels based on a poly(N-isopropylacrylamide) backbone. The hydrogels were injected in the peritoneal cavity of SR-A knockout (KO) and wild-type mice using a minimally invasive procedure and allowed to set in situ. After 24 h, the hydrogels were recovered and analyzed, the peritoneal cavity was lavaged, and cytokine concentrations were assessed by ELISA. The polyanionic hydrogels retrieved from the KO animals were found to be completely devoid of adherent leukocytes, which were present in other materials regardless of the mouse strain in which they were injected. Results from a subsequent in vitro cellular adhesion study with a RAW264.7 cell line failed to yield a similarly definitive role for SR-A in the cellular binding of a polyanionic hydrogel. Taken together, the results of this study show that SR-A mediates leukocyte adhesion to a polyanionic hydrogel in the peritoneal cavity, but other adhesion mechanisms contribute to cellular binding in vitro.