Fig. 10: Schematic summarizing the main findings of this study.
a FBRs to hydrogels injected into healthy uninjured CNS mimic natural wound healing responses to CNS tissue injury and exist on a severity spectrum that is dependent on definable material properties. This study identified that hydrogel chemistry presented to the host at the biomaterial-tissue interface determines FBRs and that CNS FBR phenotype and its severity alters hydrogel function in terms of molecular delivery and biomaterial resorption. (i) Non-ionic and anionic hydrogels demonstrated: minimal peripheral derived inflammation, minimal fibrosis, limited resorption, and enhanced molecular delivery to neurons. Cationic hydrogels provoke significant non-neural tissue (NNT) FBRs resulting in predominant inflammatory cell delivery as well as either rapid resorption (ii), or frustrated phagocytosis and persistent acute inflammation and limited resorption (iii). b FBRs to hydrogels injected into subacute CNS stroke injuries influenced molecular delivery to preserved neurons and altered CNS wound healing processes. When applied to striatal stroke, nonionic hydrogels [DCHMO–(i)] showed improved bioactive molecular delivery to neurons without significantly altering the stroke lesion core (LC). Cationic materials [DCHK–(ii) and DCHMM–(iii)] showed reduced molecular delivery efficacy and disruption of natural wound healing processes within LCs.
