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

Abstract

<div> <div> <div> <p>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. </p> </div> </div> </div>

Photo-Crosslinkable Polymeric Coatings Providing Chemically Versatile Reactive Surfaces on Various Substrates

“…To overcome this issue, we modified fGel to incorporate methacrylate units, which can act as crosslinkable units in the presence of a radical species, by reacting the primary amine with the glycidyl group in glycidyl methacrylate, i.e., fGelMA. 35,36,39 In this design, two crosslinking mechanisms are considered after UV light illumination: (i) addition of the released primary amine from NBOC in MN with DTC or glycidyl groups in the MD or MG chain and (ii) a radical-based reaction of the methacrylate in fGelMA (Scheme 4) with the use of a photo-radical generator (LAP). In the case of the MN/MG system, the vinyl groups in the fGelMA chains were bonded to each other to form interchain bridges upon exposure, with the resulting fGelMA network expected to be intertwined and physically interact with another network formed by interchain reactions between the MN and MG chains.…”

“…Methacrylate-incorporated fish skin gelatin (fGelMA) was synthesized by the reaction of fGel with GMA. 36,39 Briefly, fGel (10.0 g) was dissolved in 100 mL of DMSO, followed by stirring at 50 °C for 30 min. To tune the degree of methacrylate incorporation from low to high, 1.218 g of GMA (or 8.529 g) and 0.175 g of DMAP (or 1.222 g) were added to the fGel solution, followed by stirring at 50 °C for 2 days.…”

“…Furthermore, due to the presence of highly polar PEG units in all copolymers, dual-component systems consisting of MN and MG or MN and MD were all processable with polar solvents, e.g., water and ethanol, and readily crosslinked simply by UV light illumination, which allows defining and stabilizing an active thin film surface in a desirable region by a photolithographic manner, without any additives and heating process. We further utilized the designed materials and resulting surfaces to attain surface activeness by incorporating biologically active macromolecules via two routes: (i) the resulting thin films were further modified with the reaction of bovine serum albumin (BSA) in the presence of the remaining surface reactive groups (epoxide and DTC); (ii) the copolymers were further mixed with fish skin gelatin bearing methacrylate 35,36 to form the composite thin film, further allowing additional crosslinking in the presence of a photo-radical generator. The amount of gelatin imparting surface-active functionality was also controllable without any degradation in the crosslinking capability.…”