Regulating inflammation using acid-responsive electrospun fibrous scaffolds for skin scarless healing

Abstract

Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing.

Figure 1

(a) Photograph of a rat model; (b) implantable electrospun fibrous scaffolds; (c) schematic illustration of acid-responsive electrospun fibers; (d) AR-I-PLLA-EF before releasing; (e) AR-I-PLLA-EF after releasing in pH 5.0; (f) the cumulative release curve of drug.

Figure 2

The wound closure rate of wound healing in the skin wound repair. Error bars represent SD. Wound healing rates of SD rats compared with control group; *P < 0.05.

Figure 3

H&E staining of wounded skin repair after 3–21 days (×50).

Figure 4

Masson's trichrome stained histological sections after 3–21 days (×50).

Figure 5

Wound skin repair operation after 3–21 days for immunohistochemical detection of bFGF (×200).

Figure 6

Immunohistochemical detection of α-SMA after 14 days of the operation (×200).

Figure 7

Western blot analysis of α-SMA on the 14th day after operation. (a) The levels of α-SMA in scars of different groups by Western blot. (b) Analysis of the signal intensity of α-SMA was performed among four groups. *P < 0.05 compared to control group; **P < 0.01 compared to control group.

Figure 8

qRT-PCR analysis of the relative mRNA levels of collagen I and collagen III (a); TGF-β1 and TGF-β3 (c); MMP-1 and TIMP-1 (e), **P < 0.05 compared to control group. The ratio of collagen I/collagen III (b); TGF-β1/TGF-β3 (d); MMP-1/TIMP-1 (f) for 14 days after operation, using relative mRNA levels through qRT-PCR analysis, *P < 0.05 compared to control group.