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

Engineering composite biomaterials requires the successful integration of multiple feed- stocks 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 der- mal 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 ef- ficient chemoselective thiol-ene chemistry was utilized for the formation of composites with thio- lated lignosulfonate (TLS) and methacrylated fish gelatin (fGelMA) in the PEG(poly (ethylene gly- col))-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 evi- denced 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 signifi- cantly reduced the differential of five different fibrotic markers (COL1A1, ACTA2, TGFB1 and HIF1A) between HS and low scarring (LS) hdFBs, providing the potential utility of TLS in a bio- material scaffold to attenuate fibrotic responses.