Regenerative Potential of Hydrogels for Intracerebral Hemorrhage: Lessons from Ischemic Stroke and Traumatic Brain Injury Research

Abstract

Intracerebral hemorrhage (ICH) is a deadly and debilitating type of stroke, caused by the rupture of cerebral blood vessels. To date, there are no restorative interventions approved for use in ICH patients, highlighting a critical unmet need. ICH shares some pathological features with other acute brain injuries such as ischemic stroke (IS) and traumatic brain injury (TBI), including the loss of brain tissue, disruption of the blood–brain barrier, and activation of a potent inflammatory response. New biomaterials such as hydrogels have been recently investigated for their therapeutic benefit in both experimental IS and TBI, owing to their provision of architectural support for damaged brain tissue and ability to deliver cellular and molecular therapies. Conversely, research on the use of hydrogels for ICH therapy is still in its infancy, with very few published reports investigating their therapeutic potential. Here, the published use of hydrogels in experimental ICH is commented upon and how approaches reported in the IS and TBI fields may be applied to ICH research to inform the design of future therapies is described. Unique aspects of ICH that are distinct from IS and TBI that should be considered when translating biomaterial‐based therapies between disease models are also highlighted.

Injectable, Micellar Chitosan Self‐Healing Hydrogel for Asynchronous Dual‐Drug Delivery to Treat Stroke Rats

“…Novel delivery strategies such as noninvasive intranasal delivery and in situ brain delivery can improve drug delivery efficiency, which usually involves the use of hydrogel. [ 61 ] Owing to the highly selective nature of the BBB, classic drug delivery methods such as intravenous, intraperitoneal, and intra‐arterial injections are quite inefficient. Most of the administered drug is excreted or metabolized in the kidneys, lungs, and liver.…”

“…[ 63 ] The therapeutic benefit of hydrogel has been recently investigated in both experimental TBI (trauma to the skull) and IS (blockage of cerebral blood vessels), yet the use of hydrogel in ICH (rupture of cerebral blood vessels) therapy is still in its beginning with very few published reports. [ 61 ] To characterize the possible angiogenesis observed in the CMD hydrogel group, vascular endothelial growth factor A (VEGF‐A) and CD31 were employed to label microvascular endothelial cells and platelet endothelial cell adhesion molecules. [ 64 ] In the meantime, VEGF‐A is considered to be the dominant inducer of the growth of blood vessels.…”

Injectable Hydrogels for Nervous Tissue Repair—A Brief Review

“…Kornev et al [ 27 ] describe several requirements that biodegradable scaffolds must have: injectability, shear-thinning and self-healing, biocompatibility, low cytotoxicity, non-immunogenicity, non-mutagenicity, and promotion of cell proliferation, migration, and differentiation. Also, scaffolds must be soft and allow for the encapsulation of cells, drugs, or bioactive molecules as well as promote controlled drug delivery [ 115 , 137 ]. Table 3 displays the advances in injectable hydrogels for brain injury.…”

Applications and Mechanisms of Stimuli-Responsive Hydrogels in Traumatic Brain Injury

“…Traditional drug delivery is hampered by the presence of the BBB, making it difficult to reach the target area [ 67 ]. Hydrogels have good biocompatibility and injectability, which allows them to injected in situ and adapt to the irregularity of the injury site, and have a wide range of applications in TBI [ 68 ]. Stimuli-responsive hydrogels can respond to the inflammatory and oxidative stress microenvironment at the injury site to regulate inflammation, edema, and oxidative stress levels, and promote neurogenesis and functional recovery [ 11 ].…”