title: Biocompatible Injectable Hydrogel with Potent Wound Healing and Antibacterial Properties.
abstract: Two component injectable hydrogels that cross-link in situ have been used as noninvasive wound-filling devices, i.e., sealants. These materials carry a variety of functions at the wound sites, such as sealing leaks, ceasing unwanted bleeding, binding tissues together, and assisting in wound healing processes. However, commonly used sealants typically lack antibacterial properties. Since bacterial infection at the wound site is very common, bioadhesive materials with intrinsic antibacterial properties are urgently required. Herein, we report a biocompatible injectable hydrogel with inherent bioadhesive, antibacterial, and hemostatic capabilities suitable for wound sealing applications. The hydrogels were developed in situ from an antibacterial polymer, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and a bioadhesive polymer, polydextran aldehyde. The gels were shown to be active against both Gram-positive and Gram-negative bacteria, including drug-resistant ones such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and β-lactam-resistant Klebsiela pneumoniae. Mechanistic studies revealed that the gels killed bacteria upon contact by disrupting the membrane integrity of the pathogen. Importantly, the gels were shown to be efficacious in preventing sepsis in a cecum ligation and puncture (CLP) model in mice. While only 12.5% of animals survived in the case of mice with punctured cecam but with no gel on the punctured area (control), 62.5% mice survived when the adhesive gel was applied to the punctured area. Furthermore, the gels were also shown to be effective in facilitating wound healing in rats and ceasing bleeding from a damaged liver in mice. Notably, the gel showed negligible toxicity toward human red blood cells (only 2-3% hemolysis) and no inflammation to the surrounding tissue upon subcutaneous implantation in mice, thus proving it as a safe and effective antibacterial sealant.
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bengaluru 560064, India.
authors.forename: Jiaul
authors.initials: J
authors.lastname: Hoque
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bengaluru 560064, India.
authors.forename: Relekar G
authors.initials: RG
authors.lastname: Prakash
authors.affiliation: National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI) Ramagondanahalli , Yelahanka, Bengaluru 560064, India.
authors.forename: Krishnamoorthy
authors.identifier: 0000-0001-7495-1333
authors.initials: K
authors.lastname: Paramanandham
authors.affiliation: National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI) Ramagondanahalli , Yelahanka, Bengaluru 560064, India.
authors.forename: Bibek R
authors.initials: BR
authors.lastname: Shome
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Jakkur, Bengaluru 560064, India.
authors.forename: Jayanta
authors.identifier: 0000-0002-8068-1015
authors.initials: J
authors.lastname: Haldar
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D053138:Cyclohexenes / Q000737:chemistry; D005260:Female; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D007267:Injections / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013552:Swine; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D053138:Cyclohexenes; C413286:aglycone 4-hydroxy-2,6,6-trimethyl-1-carboxyaldehyde-1-cyclohexene; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: antibacterial activity; drug-resistant bacteria; hemostatic ability; injectable bioadhesive hydrogel; surgical site infections; wound healing