# Lignin to Materials: A Focused Review on Recent Novel Lignin Applications
## 3 Medical Applications  
### Wound Dressings  
Hydrogels are three-dimensional (3D) networks of polymers; their hydrophilic structures make them capable of absorbing and holding large amounts of water in their 3D networks [19; 20]. Hydrogels have gained significant attention in biomedical sectors because they can be used for drug delivery, tissue engineering, and antimicrobial materials [21]. Recently, lignin has been viewed as a promising material for the production of hydrogels, because lignin possesses great antioxidant and antibacterial properties [22]. Furthermore, hydrogels have a high absorption capacity, allowing them to effectively remove undesirable metabolites from the wound [23]. Due to lignin's high mechanical strength, the use of lignin in hydrogels helps protect the wound from further injury or contamination [23]. However, due to the relatively low amount of hydroxyl groups and its rigid structure, lignin requires pretreatment for it to be effectively used as a medical material. In this respect, many studies have focused on developing chemical modification strategies of lignin. Such modifications include the introduction of new active sites on lignin by combining other materials and the functionalization of the hydroxyl group to enhance its reactivity. There are several ways that lignin can be combined with other materials to construct composite wound dressings that are antimicrobial and biocompatible. A study that used a lignin model polymeric compound, dehydrogenase polymer (DHP), in alginate (Alg) hydrogel, determined that the lignin model DHP in hydrogel produced antimicrobial effects against several clinical bacterial strains and did not have toxic effects on human epithelial cells [24]. A stock suspension of 10 mg/mL DHP and 20 mg/mL Alg was used to test for antibacterial properties. The DHP-Alg demonstrated minimum inhibitory concentration values of 0.002-0.90 mg/mL and a minimum bactericidal concentration of 0.004-1.25 mg/mL. Furthermore, DHP-Alg showed higher antibacterial activity against _L. monocytogenes, P. aeruginosa, and S. Typhimurium_ than streptomycin and ampicillin [24]. The mechanism of antibacterial action was speculated to be that DHP in hydrogel interacts with bacterial cell wall synthesis and/or cell wall structure, which could lead to the disorganization of the cell wall. Although more studies need to be conducted on elucidating the antibacterial mechanism of DHP, the results show the potential application of lignin as a wound-healing agent. Lignin amine and sulfite-pulped lignin can also be used to construct two different wound dressings. Lignin amine can be synthesized from sodium lignocellulosic by a Mannich reaction; the lignin amine can be crosslinked with poly(vinyl alcohol) (PVA) to form a hydrogel. When a solution of silver nitrate was added to the lignin-based hydrogel, the biocompatible hydrogel not only demonstrated enhanced antimicrobial properties against _E. coli_ and _S. aureus_, but the hydrogel also exhibited good elasticity [25]. Additionally, the lignin obtained from sulfite pulping can be combined with chitosan dissolved in an acetic acid solution and PVA dissolved in water to form a lignin-chitosan-PVA composite hydrogel. The sulfonate groups in the lignin formed ionic bonds with amino groups in the chitosan; this is what gives the hydrogel a high mechanical strength and high antioxidant activity [23]. The lignin-chitosan-PVA composite hydrogel demonstrated inhibitory effects on _S. aureus_ by penetrating its cell membrane. Results from the study suggested that a hydrogel with a greater lignin concentration resulted in an increase in the swelling ratio, hydrophilicity, protein adsorption capacity, tensile strength, and elongation. Three-dimensional-printed wound dressings can also be constructed from lignin. Poly(lactic acid) (PLA) pellets coated with castor oil can also be combined with a small amount of Kraft lignin (3 wt % or less) and an antibiotic, tetracycline, to create a composite used for 3D printing wound dressings.