Synergetic effect of 3,4-dihydroxy-l-phenylalanine-modified poly(lactic-co-glycolic acid) nanopatterned patch with fibroblast growth factor-2 for skin wound regeneration

Nanoscale topography substrates have potential in guiding cell polarization and migration. Wound healing can be accelerated by nanotopographical substrates which provided appropriate direction to host cells around wound site. We fabricated biodegradable poly (lactic-co-glycolic acid) (PLGA) nanopatterned patch (nP-patch) using capillary force lithography method. Simple surface modification was applied using 3,4-dihydroxy-l-phenylalanine (LD), which has been reported as effective adhesion molecules with similar structure as mussel protein, to immobilize fibroblast growth factor-2 (FGF2) on PLGA patches. In present study, we hypothesized that nP-patch could be enhanced the cell migration in vitro by a guide of nanotopography and that nP-patch with soluble growth factor could accelerate skin wound healing in vivo. To investigate its nanotopographical effect on cell behavior, human dermal fibroblast (HDF) cells were cultured on nP-patch and flat PLGA patch (F-patch). The rate of surface coverage was measured on nP-patch with vertical or parallel orientation. The surface coverage rate was significantly enhanced by nP-patch with vertical orientation compared to the parallel orientation or the F-patch. We made a full thickness (Ø 18 mm) wound on the back of athymic mice and implanted PLGA patches with or without FGF2. FGF2-loaded nP-patch showed much faster wound closure in 21 days compared to others. Histological analysis showed that regenerated tissue had a similar structure as native skin. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 594-604, 2017.