Immunomodulatory Potential of Chitosan-graf t-poly(ε-caprolactone) Copolymers toward the Polarization of Bone-Marrow-Derived Macrophages

In tissue engineering, the use of biomaterials as templates or scaffolds to guide tissue development in vivo provokes the inevitable action of the immune system of the host. This induced immune response often determines the success of the scaffold, including angiogenesis and regeneration or failure causing inflammation and fibrosis. Therefore, it is crucial to predict or even better to promote the proper immune response following implantation. The aim of the present study was to evaluate the immunomodulatory potential of chitosan-graftpoly(epsilon-caprolactone) copolymers (CS-g-PCL) by analyzing the differentiation of primary bone marrow derived macrophages (BMDM) cultured in vitro on copolymer thin films. In order to evaluate the role of the chitosan content of the copolymer on macrophage polarization, two different copolymers containing SO and 78% w/w chitosan were studied. Our data from cytokines secretion detection by ELISA show that the CS-g-PCL copolymer significantly decreases the secretion of the inducible levels of pro-inflammatory cytokines IL-12/23 by 31% +/- 6, and thus possesses anti-inflammatory ability. Moreover, this anti-inflammatory action is correlated with the increased chitosan content of the copolymer. In addition, the CS-g-PCL copolymer significantly enhances the production of Arg1, the hallmark of M2 polarized macrophages, as shown by semiquantitative RT-PCR analysis, and this enhancement is 4-fold higher for the copolymer with the lower chitosan content. Although further in vivo experimentation is required to predict the outcome of the in situ engraftment of the copolymer, our results so far suggest that the CS-g-PCL copolymers possess anti-inflammatory activity and favor the transition of M1 to M2 macrophages, which are essential prerequisites for proper tissue remodeling.