Wallace Eimear J, O'Dwyer Joanne, Dolan Eimear B, Burke Liam P, Wylie Robert, Bellavia Gabriella, Straino Stefania, Cianfarani Francesca, Ciotti Gabriella, Serini Simona, Calviello Gabriella, Roche Ellen T, Mitra Tapas, Duffy Garry P
Anatomy and Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, H91 W2TY, Ireland.
Explora-Bioscience Srl, G. Peroni 386, Rome, 00131, Italy.
Adv Sci (Weinh). 2025 Feb;12(7):e2401744. doi: 10.1002/advs.202401744. Epub 2024 Dec 18.
Therapeutic proteins, the fastest growing class of pharmaceuticals, are subject to rapid proteolytic degradation in vivo, rendering them inactive. Sophisticated drug delivery systems that maintain protein stability, prolong therapeutic effects, and reduce administration frequency are urgently required. Herein, a mechanoresponsive hydrogel is developed contained within a soft robotic drug delivery (SRDD) device. In a step-change from previously reported systems, pneumatic actuation of this system releases the cationic therapeutic protein Vascular Endothelial Growth Factor (VEGF) in a bioactive form which is required for therapeutic angiogenesis, the growth of new blood vessels, in numerous clinical conditions. The ability of the SRDD device to release bioactive VEGF in a spatiotemporal manner from the hydrogel is tested in diabetic rats - a model in which angiogenesis is difficult to stimulate. Daily actuation of the SRDD device in the diabetic rat model significantly increased cluster of differentiation 31+ (CD31+) blood vessel number (p = 0.0335) and the diameter of alpha-smooth muscle actin+ (α-SMA+) blood vessels (p = 0.0025) compared to passive release of VEGF from non-actuated devices. The SRDD device combined with the mechanoresponsive hydrogel offers the potential to deliver an array of bioactive therapeutics in a spatiotemporal manner to mimic their natural release in vivo.
治疗性蛋白质是增长最快的一类药物，在体内会迅速被蛋白水解降解，从而失去活性。因此，迫切需要先进的药物递送系统来维持蛋白质稳定性、延长治疗效果并减少给药频率。在此，我们开发了一种包含在软机器人药物递送（SRDD）装置中的机械响应水凝胶。与先前报道的系统相比，该系统的一个重大突破是通过气动驱动以生物活性形式释放阳离子治疗性蛋白质血管内皮生长因子（VEGF），这在许多临床病症的治疗性血管生成（即新血管生长）中是必需的。在糖尿病大鼠（一种难以刺激血管生成的模型）中测试了SRDD装置从水凝胶中以时空方式释放生物活性VEGF的能力。与未驱动装置被动释放VEGF相比，在糖尿病大鼠模型中每天驱动SRDD装置可显著增加分化簇31 +（CD31 +）血管数量（p = 0.0335）和α-平滑肌肌动蛋白+（α-SMA +）血管直径（p = 0.0025）。SRDD装置与机械响应水凝胶相结合，有可能以时空方式递送一系列生物活性治疗剂，以模拟它们在体内的自然释放。
