开发基于硫醇-烯反应的 HA 水凝胶，可持续释放 EGF，以增强皮肤伤口愈合,Biomacromolecules

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开发基于硫醇-烯反应的 HA 水凝胶，可持续释放 EGF，以增强皮肤伤口愈合
Biomacromolecules ( IF 5.5 ) Pub Date : 2023-09-21 , DOI: 10.1021/acs.biomac.3c00810
Yerin Lee ₁ , Saebin Lim ₁ , Ji An Kim ₂ , Yoon Hong Chun ₂ , Hyun Jong Lee ₁

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这项研究开发了一种新型药物输送系统，使用透明质酸（HA）水凝胶控制表皮生长因子（EGF）的释放，以促进皮肤伤口愈合。传统的基于水凝胶的方法存在突发释放和有限的药物递送时间的问题。为了解决这个问题，我们采用生物共轭将丙烯酸酯基团引入 EGF，从而通过硫醇-烯交联与 HA 水凝胶基质形成化学键合。这种方法根据 HA 基质的降解速率实现 EGF 的持续释放，克服了基于扩散的限制。我们使用基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱法证实了丙烯酸酯基团的引入。我们评估了丙烯酸酯共轭 EGF 与 HA 基质结合后的水凝胶形态和流变特性。对 EGF 释放曲线的评估表明，与未结合的 EGF 相比，释放延迟。我们通过细胞增殖和划痕测定评估对细胞的影响，表明系统的功效。在大鼠伤口愈合模型中，水凝胶系统持续释放 EGF 促进适当的组织愈合并将其恢复到正常状态。这些发现表明，这种实用的药物输送系统，涉及生长因子或药物的修饰，以化学方式将愈合因子结合到水凝胶上，可以实现持久的效果。

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Development of Thiol–Ene Reaction-Based HA Hydrogel with Sustained Release of EGF for Enhanced Skin Wound Healing

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol–ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization–time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system’s efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.

更新日期：2023-09-21

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