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

Physicochemical properties of gelatin/hyaluronic acid printed hydrogel and incorporated with 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 Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8397, Japan
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/ )
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 enabling 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 hyaluronic acid (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 rates (WVTR) in a range of 2000-3000 gm-2day-1, which are crucial for maintaining a moist environment in 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 HDF 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 HDF attachment and proliferation, as confirmed by live and dead cell staining, also with Ki-67, 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.

Keywords
Gelatin
Hyaluronic acid
Thymoquinone
3D bioprinting
Physicochemical properties
Biocompatibility
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 hereby 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