Attenuating Fibrotic Markers of Patient-Derived Dermal Fibroblasts by Thiolated Lignin Composites

Engineering composite biomaterials requires the successful integration of multiple feedstocks to formulate a final product for functional improvement. Here we engineered biomaterial scaffolds to attenuate the fibrotic phenotype exhibited by high scarring (HS) patient-derived dermal fibroblasts (hdFBs) by valorizing lignosulfonate from waste feedstocks of lignin. We utilized phenolic functional groups of lignosulfonate to impart antioxidant properties and the cell binding domains of gelatin to enhance cell adhesion for poly(ethylene glycol)-based scaffolds. Highly efficient chemoselective thiol-ene chemistry was utilized for the formation of composites with thiolated lignosulfonate (TLS) and methacrylated fish gelatin (fGelMA) in the PEG(poly (ethylene glycol))-diacrylate matrix. Antioxidant properties of lignosulfonate was not altered after thiolation and the levels of antioxidation were comparable to a well-known antioxidant, L-ascorbic acid, as evidenced by DPPH (2,2-diphenyl-1-picrylhydrazyl) and TAC (Total Antioxidant Capacity) assays. Unlike porcine gelatin, fGelMA remained liquid at room temperature and exhibited low viscosities, resulting in no issues of miscibility when mixed with PEG. PEG-fGelMA-TLS composites significantly reduced the differential of five different fibrotic markers (COL1A1, ACTA2, TGFB1 and TGFB1) between HS and low scarring (LS) hdFBs, providing the potential utility of TLS in a biomaterial scaffold to attenuate fibrotic responses.