AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.8551
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RESEARCH ARTICLE

Physicochemical properties of gelatin/ hyaluronic acid-printed hydrogel incorporating thymoquinone: In vitro evaluation of biocompatibility for wound healing

Nur Izzah Md Fadilah1,2 ,  Yasuhiko Tabata3 ,  Manira Maarof1,2 ,  Mh Busra Fauzi1,2*
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1 Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Cheras, Kuala Lumpur, Malaysia
2 Advance Bioactive Materials-Cells UKM Research Group, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia
3 Cell Biotechnology Group, Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, South Research Bldg. No.1 (Institute for Life and Medical Sciences) 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
IJB, 8551 https://doi.org/10.36922/ijb.8551
Submitted: 15 January 2025 | Accepted: 20 February 2025 | Published: 20 February 2025
(This article belongs to the Special Issue Advances in 3D Bioprinting)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Wound healing is a multifaceted biological process that necessitates the development of advanced materials that can effectively support tissue regeneration and repair. The fabrication of bioengineered wound dressings has evolved significantly, with three-dimensional (3D) bioprinting emerging as a promising method to produce personalized, structurally stable hydrogels. In this study, we leveraged extrusion-based 3D bioprinting technology to develop gelatin-hyaluronic acid (GEL-HA) hydrogels, incorporating thymoquinone (TQ), a bioactive compound known for its regenerative properties. The use of 3D printing allowed for precise control over the scaffold’s architecture, optimizing its compressive strength and resilience while creating a bioactive, biocompatible platform for wound healing applications. This enables precise control over their architecture and mechanical properties to enhance wound healing where it offers promising potential as biocompatible scaffolds for wound healing applications due to their favorable physicochemical properties and ability to promote cell proliferation and migration. GEL-HA hydrogels were fabricated with varying HA concentrations (0.1–1.0 wt%), and the effects on the gelation process and physical characteristics were evaluated. Results showed that the ideal gelation temperature for the GEL-HA hydrogel was 22 °C, with the inclusion of HA reducing polymerization time. The printed hydrogels exhibited high water retention (>1000%) and satisfactory mechanical properties, with a degree of crosslinking of up to 40.21%. Furthermore, the hydrogels demonstrated a low biodegradation rate (less than 0.300 mg/h) and favorable water vapor transmission rate (WVTR) in a range of 2000– 3000 gm–2day–1, which are crucial for maintaining a moist environment for wound healing. The incorporation of TQ further enhanced the biocompatibility and cellular proliferation of human dermal fibroblasts (HDFs). Cell viability assays indicated that TQ promoted HDFs growth at concentrations of 0.005–0.1 μg/mL without toxicity. Moreover, the wound scratch assay demonstrated that TQ facilitated cell migration, with the optimum concentration of 0.1 μg/mL showing the most significant effect. The GEL-HA-TQ hydrogel also supported HDFs attachment and proliferation, as confirmed by live and dead cell staining, also with Ki67 level assessment, and collagen type-I immunocytochemistry. These findings suggest that GEL-HA hydrogels, combined with TQ, provide a promising and biocompatible platform for wound healing. It effectively promotes cell viability, migration, and extracellular matrix synthesis, which could be beneficial in regenerative medicine and tissue engineering applications.

Graphical abstract
Keywords
3D bioprinting
Biocompatibility
Gelatin
Hyaluronic acid
Physicochemical properties
Thymoquinone
Wound healing
Funding
This study was supported by grants from the Geran Fundamental Fakulti Perubatan (GFFP), Universiti Kebangsaan Malaysia with a code project (Grant Code: FF-2022-310).
Conflict of interest
The authors declare that they have no conflict of interest.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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