Controlled delivery of a neurotransmitter–agonist conjugate for functional recovery after severe spinal cord injury

Engineered Multifunctional Zinc–Organic Framework-Based Aggregation-Induced Emission Nanozyme for Accelerating Spinal Cord Injury Recovery

“…The expression of GFAP was significantly lower in the treatment groups than in the injury group, whereas that of NFH was lower in the injury group than in the treatment groups (Figure 6F), indicating that Zn@MOF and Zn@MOF-TPD promote neuronal regeneration by inhibiting glial scar formation. These results are consistent with those of previous studies, 36,48 indicating that scavenging ROS and inhibiting MMP-9 expression can reduce scar formation and improve neurogenesis in the spinal cord.…”

“…ROS-induced activation of pro-inflammatory genes may lead to inflammation and aggravate oxidative stress and tissue injury, including neuronal death, during secondary SCI . The progress of SCI involved in a time-dependent multiphasic response of cellular infammation, where the initial phases of cellular infammation were composed of an early peak of neutrophils 1-day postinjury, followed by a peak of macrophages/microglia 7-day postinjury. − Especially, the production of cytokine by astrocytes is primarily involved in promoting migration of anti-inflammatory (M2) macrophages . As for the Zn@MOF-TPD-treated SCI group, there are infiltration of macrophage immune populations, and we have performed the infiltration effects of macrophages by immunofluorescence staining of CD86 and CD206.…”

Reactive oxygen species targeted biomaterials for spinal cord injury therapy

“…From a combination therapy perspective, [2,17,[65][66][67] enzymatic biomaterials currently demonstrate limitations in effectively synergizing with other treatment modalities, and further exploration of this challenge is needed in the context of SCI. Nonenzymatic biomaterials, including both inorganic and organic core types, are commonly paired with cell therapy, [35,45,49,65,68,69] protein therapy, [46,68,70,71] neuromodulation therapy, [2,51,72] or gene regulation therapy [41,73] for SCI treatment. Combination therapy approaches appear essential for achieving the ultimate goal of SCI repair.…”

“…Zuo et al developed a ROS-responsive prodrug release system for treating SCIs based on phenylboronic-based biomaterials. [51] The ROS-responsive and scavenging attributes were verified using a DCFH-DA assay and an oxidation-triggered release experiment. The pharmacological approach combined neuroprotection and targeted neuromodulation, leading to substantial functional restoration post-SCI, and represents a promising direction for SCI therapeutics to integrate neuroprotective strategies with precise drug delivery.…”

Robust and Multifunctional Nanoparticles Assembled from Natural Polyphenols and Metformin for Efficient Spinal Cord Regeneration

“…Recently, great progress has also been made in activating endogenous neural stem cells (NSCs) to repair the structure and function of SCI in animal models via bioactive drugs, polymer scaffolds, and molecules. − For example, in addition to its therapeutic effect on diabetes, metformin (Met) has been demonstrated to efficiently induce endogenous NSCs to proliferate and repair damaged structures in animal models of brain injury and stroke. − In addition to supporting NSCs transplantation, polymer scaffolds can also support local release of bioactive molecules, induce endogenous NSCs proliferation and differentiation, and then enhance function repair. , More importantly, it was also found that the strategies to expand the limited regeneration by activating the proliferation of endogenous NSCs or transplanting exogenous stem cells are also affected by the harsh microenvironment at the injury sites, which could reduce stem cell survival and lead to the stem cells differentiating into astrocytes instead of neurons and oligodendrocytes. ,− Therefore, the integrated therapy strategy via improving the harsh microenvironment as well as promoting endogenous NSCs to repair the structure of SCI using robust biomaterials is considered to be one of the most promising therapeutic strategies for SCI repair. , Functional nanomaterials are an emerging and highly promising option for integrated therapy strategies, by combining different biologically active drugs into nanoparticles (NPs) or other nanoscale devices through covalent or noncovalent combinations . It is worth noting that for the central nervous system (CNS) injury diseases, including SCI, brain injury, and cerebral hemorrhage, due to the dysfunction of the integrity of the blood–brain/spinal barrier and the increase of vascular permeability, as well as the formation of excessive ROS and the acidic microenvironment at the injury site, nanoscale components have been confirmed to be significantly enriched at the injury site. − In addition, in terms of drug delivery, functional nanomaterials also have the following advantages. First, nanomaterials could solve the problems of poor water solubility and prohibit the active molecules from fast clearance to prolong the action duration .…”