Bioactive Limonene-Derived Oligomer in Gelatin Hydrogels: Impact of Cross-Linking Chemistry on Physicochemical Properties and Wound Healing Performance
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Antioxidant photo-cross-linkable hydrogels have garnered significant interest for biomedical applications, but challenges such as additive thermal instability and interference with cross-linking remain. Here, we report the first systematic comparison of a limonene-derived oligomer (PLM) incorporated into two distinct photo-cross-linkable gelatin platforms, highlighting how cross-linking chemistry governs antioxidant performance and network integrity. PLM was incorporated at 5% and 10% (w/w, relative to gelatin), comparing the performance of gelatin-methacryloyl (GelMA) and gelatin-norbornene (GelNB) hydrogels in terms of cross-linking efficiency, antioxidant retention, release profile, and biocompatibility upon PLM incorporation. While PLM negatively affected the physicochemical properties of GelMA, its incorporation into GelNB did not show similar drawbacks. High-resolution magic angle spinning (HR-MAS) 1 H NMR spectra revealed a significant drop in double bond consumption (DC) for GelMA, from 71% to 46% in GelMA/PLM10. In contrast, GelNB demonstrated nearly complete DC (98%) even in GelNB/PLM10, indicating efficient cross-linking despite the presence of the antioxidant. Release profiles suggested a Fickian diffusion mechanism, with higher diffusivity values for GelNB, further highlighting differences in the matrix networks. Additionally, while PLM increased GelMA’s antioxidant capacity from 6% to 19%, GelNB with PLM showed an impressive enhancement, reaching up to 90%. Both GelMA and GelNB hydrogels with 5% (w/w) PLM supported healthy cell morphology and viability above 85% over 7 days. In-vivo, GelNB/PLM5 demonstrated excellent biocompatibility over 18 days, with no significant inflammation compared to controls. Notably, this sample achieved the highest wound closure (94.90%) by day 18, outperforming the positive control (Sorbalgon). Overall, the results demonstrate that the thiol–ene cross-linking pathway enables superior preservation of antioxidant functionality and network integrity, positioning GelNB/PLM5 as a promising candidate for advanced wound-healing applications.
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo, Fonds Wetenschappelijk Onderzoek, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universiteit Gent, Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii, Vlaamse regering, Ministerul Cercetării şi Inovării
Awards: Magnetic resonance equipment for advanced material research: molecular characterisation of solid, soft, homogeneous and heterogeneous matter for the development of advanced functional materials and chemical catalysis, Development of films and hydrogels containing terpenes or derivative oligomers for active packaging and multifunctional medical devices applications, G2492948467, G4070301619, G523807596, Exploiting polymersomes to create 'smart' wound dressings with diagnostic and antimicrobial capabilities, G6523329436, G7081156356, G7939529489
OpenAlex ID: W7117133898