The regenerative potential of injectable peptide hydrogels for intracerebral haemorrhage therapy

Abstract

Intracerebral haemorrhage (ICH) is a subtype of stroke that makes up around 10-15% of cases in western countries. Although ICH is the deadliest form of stroke, current treatment options are limited, and ICH survivors are often left with life-changing impairments. The significant unmet clinical need and socioeconomic burden of ICH means novel regenerative medicine approaches are gaining interest. To facilitate regeneration of the ICH lesion, injectable biomimetic hydrogels are proposed as both scaffolds for endogenous repair and delivery platforms for pro-regenerative therapies. In the current work, a novel self-assembling peptide hydrogel (SAPH) from Manchester BIOGEL was administered to the lesion in the chronic phase of ICH, in a rat model. To determine whether the intervention was safe, feasible and stimulated regeneration after ICH, a battery of functional outcome measures, histological markers of damage and repair, functional measures of cerebral blood flow (CBF) and blood-brain-barrier (BBB) integrity, and RNA-sequencing were investigated. The results demonstrated that the novel SAPH was safe and well-tolerated, and was retained in the lesion for several weeks, where it allowed infiltration of host cells. However, the material had largely neutral effects on functional outcomes, expression of angiogenic and neurogenic markers, CBF, BBB integrity and gene expression after ICH, compared to ICH controls. Overall, the results show that the novel hydrogel was safe when injected into the brain but in order to elicit a regenerative effect, the material may need to be functionalised or combined with an adjunct therapy. In addition to the hydrogel-related findings, the work presented contributes several novel findings on the progression of ICH into the chronic phase and is the first report using advanced functional imaging and RNAseq as late as eight weeks post-ICH, in an experimental model.

Date of Award	31 Dec 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Alberto Saiani (Supervisor), Stuart Allan (Supervisor), Catherine Lawrence (Supervisor) & Emmanuel Pinteaux (Supervisor)