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Review
. 2025 Oct 15:683:125929.
doi: 10.1016/j.ijpharm.2025.125929. Epub 2025 Jul 23.

Dual cross-linked hydrogels as promising materials for drug delivery

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Free article
Review

Dual cross-linked hydrogels as promising materials for drug delivery

Carsten Damm et al. Int J Pharm. .
Free article

Abstract

Hydrogels have long found their place as versatile materials for drug delivery due to their biocompatibility, tunable properties and tissue-like mechanical behavior. Despite these advantages they suffer from a multitude of drawbacks, ranging from lacking injectability and low mechanical strength to short drug release times. These factors limit their potential clinical applications. Dual cross-link hydrogels are a versatile tool to address these shortcomings. By combining covalent with dynamic-covalent and physical cross-linking they create smarter, stronger and more versatile hydrogels, broadening their applicability. This review aims to bridge the gap between traditional hydrogels and emerging dual cross-linked hydrogels by providing an overview of the chemistries involved. We discuss the most popular cross-linking strategies and how these can be used to address specific challenges in hydrogel design. Furthermore we highlight how recent research has utilized these promising materials to enable the application of hydrogels in ever more demanding environments.

Keywords: Dual cross-link hydrogels; Hybrid cross-linking; Parenteral drug delivery; Polymers; Sustained release; Tissue engineering.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Achim Goepferich reports financial support was provided by Federal Ministry of Education and Research Bonn Office. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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