Macrophage polarization in wound healing: role of aloe vera/chitosan nanohydrogel

The balance between M1 and M2 macrophages plays an important role in wound healing. Interestingly, this immune response can be modulated by natural biomaterials such as chitosan nanohydrogel (Ch) and aloe vera (AV). Therefore, we aimed to improve wound recovery response by exploiting the potential healing properties of Ch and AV. Wounds were created in rats and were treated daily with either saline (control), AV, Ch, or different ratios of AV (volume):Ch (weight) (1:1), (2:1), and (3:1). M1 (iNOS, TNF-alpha) and M2 (CD163, TGF-beta) responses were analyzed at days 3, 7, 14, 21, and 28. Wound healing increased within the third and seventh days in AV-Ch (3:1) (P < 0.001 and P < 0.002, respectively). In the treated groups, immunohistochemistry of iNOS expression decreased on the third day (P < 0.0001) while CD163 increased (P < 0.0001) on the 3rd, 7th, and 14th days. The gene expression of TGF-beta decreased on the third day in AV group (P < 0.03) and on the 21st and 28th days in Ch-treated group (P < 0.00). TNF-alpha expression decreased in AV, Ch, and AV-Ch (3:1 v/w) on the 14th and 28th days (P < 0.00). TGF-beta and TNF-alpha proteins decreased on the 28th day compared to the control and AV-Ch (3:1 v/w), respectively. AV-Ch (1 and 3:1 v/w) and Ch resulted in optimum wound repair by decreasing M1 after 3 days and increasing M2 after 14. Thus, Ch nanohydrogel, especially in combination with 1:1 and 1:3 ratio to AV, could be a proper candidate for modulating macrophages in response to wound healing.