School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Acta Biomater. 2023 Mar 1;158:87-100. doi: 10.1016/j.actbio.2023.01.013. Epub 2023 Jan 12.
Electrically modulated delivery of proteins provides an avenue to target local tissues specifically and tune the dose to the application. This approach prolongs and enhances activity at the target site whilst reducing off-target effects associated with systemic drug delivery. The work presented here explores an electrically active composite material comprising of a biocompatible hydrogel, gelatin methacryloyl (GelMA) and a conducting polymer, poly(3,4-ethylenedioxythiophene), generating a conducting polymer hydrogel. In this paper, the key characteristics of electroactivity, mechanical properties, and morphology are characterized using electrochemistry techniques, atomic force, and scanning electron microscopy. Cytocompatibility is established through exposure of human cells to the materials. By applying different electrical-stimuli, the short-term release profiles of a model protein can be controlled over 4 h, demonstrating tunable delivery patterns. This is followed by extended-release studies over 21 days which reveal a bimodal delivery mechanism influenced by both GelMA degradation and electrical stimulation events. This data demonstrates an electroactive and cytocompatible material suitable for the delivery of protein payloads over 3 weeks. This material is well suited for use as a treatment delivery platform in tissue engineering applications where targeted and spatio-temporal controlled delivery of therapeutic proteins is required. STATEMENT OF SIGNIFICANCE: Growth factor use in tissue engineering typically requires sustained and tunable delivery to generate optimal outcomes. While conducting polymer hydrogels (CPH) have been explored for the electrically responsive release of small bioactives, we report on a CPH capable of releasing a protein payload in response to electrical stimulus. The composite material combines the benefits of soft hydrogels acting as a drug reservoir and redox-active properties from the conducting polymer enabling electrical responsiveness. The CPH is able to sustain protein delivery over 3 weeks, with electrical stimulus used to modulate release. The described material is well suited as a treatment delivery platform to deliver large quantities of proteins in applications where spatio-temporal delivery patterns are paramount.
电调制蛋白传递提供了一种专门靶向局部组织并根据应用调整剂量的途径。这种方法延长并增强了靶位的活性，同时减少了与全身药物递送相关的脱靶效应。本文探讨了一种由生物相容性水凝胶、明胶甲基丙烯酰（GelMA）和导电聚合物聚（3,4-亚乙基二氧噻吩）组成的电活性复合材料，生成导电聚合物水凝胶。本文使用电化学技术、原子力显微镜和扫描电子显微镜对电活性、力学性能和形态等关键特性进行了表征。通过将细胞暴露于材料中来确定细胞相容性。通过施加不同的电刺激，可以在 4 小时内控制模型蛋白的短期释放曲线，从而实现可调节的释放模式。接着进行了 21 天的延长释放研究，揭示了凝胶 MA 降解和电刺激事件共同影响的双模态释放机制。这些数据表明，该材料具有电活性和细胞相容性，适合在 3 周内输送蛋白载药。该材料非常适合用于组织工程应用中的治疗输送平台，在这些应用中需要针对特定组织和时空控制药物输送。
在组织工程中使用生长因子通常需要持续和可调节的输送以产生最佳效果。虽然导电聚合物水凝胶（CPH）已被探索用于响应电刺激释放小生物活性物质，但我们报告了一种能够响应电刺激释放蛋白载药的 CPH。该复合材料结合了软水凝胶作为药物储库的优点和导电聚合物的氧化还原活性，使其具有电响应性。CPH 能够在 3 周内持续输送蛋白，通过电刺激来调节释放。所描述的材料非常适合作为治疗输送平台，用于在需要时空输送模式的应用中输送大量蛋白质。
