Biodegradable microparticles are useful vehicles for the controlled release of bioactive molecules in drug delivery, tissue engineering and biopharmaceutical applications. We developed dexamethasone (Dex) encapsulation into tyramine-substituted hyaluronic acid microparticles (Dex-HA-Tyr Mp) mediated by horseradish peroxidase (HRP) crosslinking using a microfluidic device and infollowing crosslinked gelatin (Gela) with proanthocyanidin (PA) as a semi-confined bed hydrogel for the repair of sciatic tissue injury. It was found that the simultaneous use of Dex-HA-Tyr Mp and cross-linked Gela-PA hydrogel improved the physical properties of the hydrogel, including mechanical strength and degradability. The designed composite also provided a sustained release system for Dex delivery to the surrounding sites, demonstrating the applicability of the fabricated hydrogel composite for sciatic nerve tissue engineering and regeneration. The encapsulated cells were viable and showed adequate growth ability and morphogenesis during prolonged incubation in Gela-PA/HA-Tyr Mp hydrogel compared to control conditions. Interestingly, histological analysis revealed a significant increase in the number of axons in the injured sciatic nerve following treatment with Dex-HA-Tyr Mp and injectable Gela-PA hydrogel compared to other control groups. In conclusion, the results demonstrated that fabricated Dex-loaded MPs and injectable hydrogel from biomimetic components are suitable systems for sustained delivery of Dex with adequate biocompatibility and the approach may have potential therapeutic applications in peripheral nerve regeneration.

Graphical Abstract

中文翻译：

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透明质酸微粒和原花青素明胶水凝胶在坐骨组织再生中释放地塞米松

可生物降解的微粒是药物输送、组织工程和生物制药应用中生物活性分子受控释放的有用载体。我们将地塞米松 (Dex) 封装到酪胺取代的透明质酸微粒 (Dex-HA-Tyr Mp) 中，通过使用微流体装置的辣根过氧化物酶 (HRP) 交联介导，然后使用原花青素 (PA) 作为半交联明胶 (Gela)。约束床水凝胶用于修复坐骨组织损伤。结果发现，同时使用Dex-HA-Tyr Mp和交联Gela-PA水凝胶可以改善水凝胶的物理性能，包括机械强度和可降解性。设计的复合材料还提供了持续释放系统，用于将 Dex 递送到周围部位，证明了制造的水凝胶复合材料对于坐骨神经组织工程和再生的适用性。与对照条件相比，封装的细胞在 Gela-PA/HA-Tyr Mp 水凝胶中长时间孵育期间是可行的，并且显示出足够的生长能力和形态发生。有趣的是，组织学分析显示，与其他对照组相比，用 Dex-HA-Tyr Mp 和可注射 Gela-PA 水凝胶治疗后，受伤坐骨神经的轴突数量显着增加。总之，结果表明，由仿生成分制成的负载 Dex 的 MP 和可注射水凝胶是持续递送 Dex 的合适系统，具有足够的生物相容性，并且该方法可能在周围神经再生中具有潜在的治疗应用。

图形概要