Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration

Abstract

Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain.

Advancements in Hydrogel Application for Ischemic Stroke Therapy

“…They found that the therapeutic window is dependent on a tissue cavity that allowed the bio-scaffold to be delivered. An optimal therapeutic time window for bio-scaffold-triggered regeneration of brain tissue and recovery occurred between 14 days and 28 days poststroke [ 71 ]. Silk has been used in humans for a long time [ 72 ].…”

Implantable Devices for the Treatment of Breast Cancer

“…Over the last one-decade, significant progress was made towards understanding the implantable therapeutic devices and its interaction with the human immune system [69,70]. Human immune cells play a significant role in successful implantation of these devices and their function in the body for an extended period [71][72][73][74]. In this regard, mouse or rat models play a significant role in understanding this process, even though it is not quite similar to the human immune system.…”

Clickable Biomaterials for Modulating Neuroinflammation

“…Interestingly, the phenotype induced by exposure to ECM scaffolds appears functionally distinct from canonical anti-inflammatory phenotypes, suggesting the response is more nuanced and requires additional study [ 157 ]. Nonetheless, one aspect is clear: decellularized ECM in its native, structured form or as an injectable hydrogel is an effective scaffold for immunomodulation and tissue repair, including in the CNS [ 159 , 160 , 161 , 162 ].…”