The effect of chemically modified alginates on macrophage phenotype and biomolecule transport

Macrophage (M phi) reprogramming has received significant attention in applications such as cancer therapeutics and tissue engineering where the host immune response to biomaterials is crucial in determining the success or failure of an implanted device. Polymeric systems can potentially be used to redirect infiltrating M1 M phi s toward a proangiogenic phenotype. This work exploits the concept of M phi reprogramming in the engineering of materials for improving the longevity of tissue engineering scaffolds. We have investigated the effect of 13 different chemical modifications of alginate on M phi phenotype. Markers of the M1 responsetumor necrosis factor- (TNF-) and inducible nitric oxide synthaseand the M2 responsearginasewere measured and used to determine the ability of the materials to alter M phi phenotype. It was found that some modifications were able to reduce the pro-inflammatory response of M1 M phi s, others appeared to amplify the M2 phenotype, and the results for two materials suggested they were able to reprogram a M phi population from M1 to M2. These findings were supplemented by studies done to examine the permselectivity of the materials. Diffusion of TNF- was completely prevented through some of these materials, while up to 84% was found to diffuse through others. The diffusion of insulin through the materials was statistically consistent. These results suggest that the modification of these materials might alter mass transport in beneficial ways. The ability to control polarization of M phi phenotypes with immunoprotective materials has the potential to augment the success of tissue engineering scaffolds. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1707-1719, 2016.