Biology subjects

Abdelrahman, Z.

Publications and source records attributed to Abdelrahman, Z..

3 recordsLinked to original sources

bioRxiv2022

Porous microneedle patch with sustained exosomes delivery repairs severe spinal cord injury

1.Mesenchymal stem cell-derived exosome (MSC-EXO) transplantation has been suggested as an efficacious treatment to suppress spinal cord injury (SCI)-triggered neuroinflammation. However, an ethically acceptable method to continuously deliver MSC-EXOs to acute spinal lesions, without damaging nearby tissues/axons, has never been achieved. In this study, we fabricated a device comprising a patch containing MSCs and a microneedle array (MN-MSC patch) to treat severe SCI. When topically applied to an acute spinal lesion beneath the spinal dura, the soft microneedle (MN) array with reasonable mechanical strength avoided damaging the nearby spinal tissues, and the porous microstructure of MNs facilitated highly efficient MSC-EXO delivery. With the capacity for sustained delivery of MSC-EXOs, the MN-MSC patch was evaluated in a contusive rat SCI model. The MSCs encapsulated in the patch could survive for at least 7 days, encompassing the optimal time window for downregulating SCI-triggered neuroinflammation. As a result, MN-MSC patch treatment led to reduced cavity and scar tissue formation, greater angiogenesis, and improved survival of nearby tissues/axons. Remarkably, rats treated by this method achieved superior muscle control and exhibited robust hindlimb locomotion functional recovery. Conclusively, the MN-MSC patch device proposed here overcomes the current dilemma between treatment efficacy and ethical issues in treating acute SCI.

bioengineering↗

bioRxiv2022

Injectable hydrogel embedded with mesenchymal stem cells repairs severe spinal cord injury

Mesenchymal stem cell (MSC) transplantation was suggested as a promising approach to treat spinal cord injury (SCI). However, the heterogeneity of MSC and the lack of appropriate delivery methods impede its clinical application. To tackle these challenges, we first generated human MSCs derived from a single cell with a great homogeneity of batch quality and then developed a biocompatible injectable hydrogel to embed these cells to treat severe SCI. In a clinically relevant rat severe SCI model, we showed that the injection of MSCs with injectable hydrogel into the lesion site promoted robust functional recovery, while the intrathecal delivery of MSCs only resulted in limited therapeutic effects. Mechanistically, the hydrogel protected MSCs from the damage of harmful neuroinflammatory microenvironment in the spinal cord lesion. The hydrogel with the survived MSCs ameliorates the neuroinflammatory microenvironment of spinal cord lesion, preventing cavity formation and leads to the remnant of spared axons/tissues, which results in a better prognosis in the end.

bioengineering↗

bioRxiv2022

Improving functional recovery after severe spinal cord injury by a noninvasive dual functional approach of neuroprotection and neuromodulation

Despite tremendous unmet medical needs, there is no effective pharmacological treatment to promote functional recovery after spinal cord injury (SCI). Although multiple pathological events have been implicated in SCI, the development of a noninvasive pharmacological approach to simultaneously target the different mechanisms involved in SCI remains a formidable challenge. In this study, we report the development of a noninvasive nanodrug delivery system that consists of ROS-responsive amphiphilic copolymers and an encapsulated neurotransmitter-conjugated KCC2 agonist. We show that upon intravenous administration, the nanodrugs were able to enter the injured spinal cord due to blood spinal cord barrier disruption and ROS-responsive disassembly. Remarkably, once in the injured spinal cord, these nanodrugs exhibited dual functions: scavenging ROS accumulated in the lesion to protect spared connections and increasing neuronal excitability in the injured spinal cord through targeted delivery of the KCC2 agonist to inhibitory neurons. Thus, the noninvasive treatment led to significant functional recovery in the rats with contusive SCI. Together, these findings provide a much-needed translational pharmacological approach for treating severe SCI.

neuroscience↗