Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins

Eimear J Wallace; Joanne O'Dwyer; Eimear B Dolan; Liam P Burke; Robert Wylie; Gabriella Bellavia; Stefania Straino; Francesca Cianfarani; Gabriella Ciotti; Simona Serini; Gabriella Calviello; Ellen T Roche; Tapas Mitra; Garry P Duffy

doi:10.1002/advs.202401744

Actuation-Mediated Compression of a Mechanoresponsive Hydrogel by Soft Robotics to Control Release of Therapeutic Proteins

Adv Sci (Weinh). 2024 Dec 18:e2401744. doi: 10.1002/advs.202401744. Online ahead of print.

Authors

Eimear J Wallace^{1

2}, Joanne O'Dwyer³, Eimear B Dolan^{1

4

5}, Liam P Burke^{1

6

7}, Robert Wylie¹, Gabriella Bellavia², Stefania Straino², Francesca Cianfarani², Gabriella Ciotti², Simona Serini⁸, Gabriella Calviello⁸, Ellen T Roche^{9

10

11}, Tapas Mitra^{1

4}, Garry P Duffy^{1

4

12}

Affiliations

¹ Anatomy and Regenerative Medicine Institute (REMEDI), School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, H91 W2TY, Ireland.
² Explora-Bioscience Srl, G. Peroni 386, Rome, 00131, Italy.
³ Pharmacology and Therapeutics, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, H91 W2TY, Ireland.
⁴ CÚRAM, SFI Research Centre for Medical Devices, University of Galway, Galway, H91 W2TY, Ireland.
⁵ Biomedical Engineering, School of Engineering, University of Galway, Galway, H91 HX31, Ireland.
⁶ Antimicrobial Resistance and Microbial Ecology Group, School of Medicine, College of Medicine Nursing and Health Sciences, University of Galway, Galway, H91 DK59, Ireland.
⁷ Centre for One Health, Ryan Institute, University of Galway, Galway, H91 DK59, Ireland.
⁸ Department of Translational Medicine and Surgery, Section of General Pathology, Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo F. Vito, Rome, 1-00168, Italy.
⁹ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 01239, USA.
¹⁰ Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA, 02139, USA.
¹¹ Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
¹² SFI Centre for Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin, Dublin, D02 W9K7, Ireland.

PMID: 39692747
DOI: 10.1002/advs.202401744

Abstract

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.

Keywords: actuation; controlled drug delivery; hydrogels; soft robotics; therapeutic proteins.

Abstract

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