Towards clinical translation of ‘second-generation’ regenerative stroke therapies: hydrogels as game changers?

• Published in: Trends in biotechnology (Regular ed.) 2022-06, Vol.40 (6), p.708-720
• Main Authors: Totten, John D., Alhadrami, Hani A., Jiffri, Essam H., McMullen, Calum J., Seib, F. Philipp, Carswell, Hilary V.O.
• Format: Article
• Language: English
• Subjects: Binding sites; Biocompatibility; Biodegradation; biomaterial technology; brain repair; Clinical trials; Extracellular matrix; hydrogel matrix; Hydrogels; Ischemia; Microenvironments; Pathology; Patients; Payloads; Recovery (Medical); scaffold; Stem cells; Stroke; Tissue engineering; Translation
• ISSN: 0167-7799; 1879-3096
• DOI: 10.1016/j.tibtech.2021.10.009

Stroke is an unmet clinical need with a paucity of treatments, at least in part because chronic stroke pathologies are prohibitive to ‘first-generation’ stem cell-based therapies. Hydrogels can remodel the hostile stroke microenvironment to aid endogenous and exogenous regenerative repair processes. However, no clinical trials have yet been successfully commissioned for these ‘second-generation’ hydrogel-based therapies for chronic ischaemic stroke regeneration. This review recommends a path forward to improve hydrogel technology for future clinical translation for stroke. Specifically, we suggest that a better understanding of human host stroke tissue–hydrogel interactions in addition to the effects of scaling up hydrogel volume to human-sized cavities would help guide translation of these second-generation regenerative stroke therapies. The stroke cavity is an ideal site for administration, being closest to a zone of neuroplasticity and able to accommodate hydrogels without compressing surrounding tissue. However, it is prohibitive to first-generation regenerative stroke therapies as it lacks an extracellular matrix; is surrounded by a glial scar; and is filled with extracellular fluid, debris, and inflammatory mediators.Hydrogels can remodel the hostile stroke cavity to be more receptive to repair due to their innate anti-inflammatory properties, good space conformity, ability to deliver a playload, and interface with the glial scar.Hydrogel 3D structure and tuneable mechanics provide physical support for endogenous and exogenous repair processes.Hydrogels are used extensively in the clinic, yet no clinical trials have been successfully commissioned to explore the potential of regenerative hydrogels in the treatment of chronic stroke.