Dual cross-linked gellan gum/gelatin-based multifunctional nanocomposite hydrogel scaffold for full-thickness wound healing

Hemant Singh; Indu Yadav; Wajid Mohammad Sheikh; Aniruddha Dan; Zenab Darban; Showkat Ahmad Shah; Narayan Chandra Mishra; Syed Shahabuddin; Shabir Hassan; Showkeen Muzamil Bashir; Mukesh Dhanka

doi:10.1016/j.ijbiomac.2023.126349

Dual cross-linked gellan gum/gelatin-based multifunctional nanocomposite hydrogel scaffold for full-thickness wound healing

Int J Biol Macromol. 2023 Aug 15:251:126349. doi: 10.1016/j.ijbiomac.2023.126349. Online ahead of print.

Authors

Affiliations

¹ Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, India.
² Polymer and Process Engineering, Indian Institute of Technology Roorkee, Uttarakhand, India.
³ Biochemistry & Molecular Biology Lab, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar, Jammu and Kashmir, India.
⁴ Department of Chemistry, Pandit Deendayal Energy University, Gandhinagar, Gujarat, India.
⁵ Division of Veterinary Pathology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar, Jammu and Kashmir, India.
⁶ Polymer and Process Engineering, Indian Institute of Technology Roorkee, Uttarakhand, India. Electronic address: narayan.mishra@pe.iitr.ac.in.
⁷ Department of Biology, Khalifa University, Abu Dhabi, United Arab Emirates.
⁸ Biochemistry & Molecular Biology Lab, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar, Jammu and Kashmir, India. Electronic address: showkeen.muzamil82@gmail.com.
⁹ Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, India. Electronic address: mukesh.d@iitgn.ac.in.

PMID: 37591426
DOI: 10.1016/j.ijbiomac.2023.126349

Abstract

Biological macromolecules are excellent materials for wound dressing owing to their similar structure to the extracellular matrix and adjustable physicochemical properties. This research focuses on fabricating biological macromolecule-based hydrogel with desirable antibacterial, antioxidant, controlled drug release, cytocompatibility, and wound healing properties. Herein, different concentrations of nanoceria (NC) and flurbiprofen (FLU) drug-loaded gellan gum/gelatin (GG/Ge) based dual crosslinked (Ionic and EDC/NHS coupling) hydrogels were engineered. All fabricated hydrogels were hydrophilic, biodegradable, good strength, porous, antioxidant, hemocompatible and cytocompatible. Among all, hydrogel loaded with 500 μg/ml NC (GG/Ge/NC@FLU) exhibited desirable antioxidant, antibacterial (killed Staphylococcus aureus and Escherichia coli within 12 h), hemocompatible, cytocompatible, supports oxidative-stressed L929 cell growth and acted as a controlled release matrix for FLU, following Fickian diffusion, Peppas Sahlin and Korsmeyer-Peppas drug release models. Furthermore, nanocomposite hydrogel (GG/Ge/NC@FLU)-treated wounds of rats on day 14 demonstrated significantly higher collagen synthesis, nearly 100 % wound contractions, and efficiently decreased the expression of TNF-α and IL-1 while increasing the production of IL-10 and TNF-ß3, indicating antiinflammatory activity, and effectively reduced the expression of VEGF gene indicating effective angiogenesis than all other controls. In conclusion, the fabricated multifunctional GG/Ge/NC@FLU nanocomposite hydrogel shows promising potential for effectively treating full-thickness wound healing in a rat model.

Keywords: Full-thickness wound healing; Gelatin; Gellan gum.