Sen Lin

Background: Secondary pathology after acute spinal cord injury (SCI) is driven by pathological iron accumulation, reactive oxygen species (ROS) overproduction, and mitochondrial failure, which together sustain chronic neuroinflammation. Methylprednisolone (MP), the most widely used ROS-scavenging agent for acute SCI, provides limited clinical benefit and carries considerable side effects. To address this, we engineered zinc hexacyanoferrate nanoenzymes (ZnHPB) that chelate excess ferrous ions while displaying intrinsic SOD- and CAT-like activities, attenuating oxidative injury at its source rather than merely suppressing downstream inflammation. The defining feature of ZnHPB is a Fe(II)-driven self-reinforcing antioxidant loop in which captured ferrous species are converted into mixed-valence Prussian-blue phases, breaking the Fenton cascade that underpins iron- and ROS-driven secondary injury. Methods: ZnHPB was prepared by polyvinylpyrrolidone-directed self-assembly and characterized for physicochemical and enzyme-mimetic properties. In vitro efficacy was evaluated in H₂O₂-challenged BV2 microglia in parallel with MP. C57BL/6 mice subjected to T8-T9 contusion SCI received ZnHPB (5 mg/kg, i.p.) under preventive or post-injury dosing regimens for 28 days, with a 60-day safety assessment. Outcome measures included cell viability, ROS levels, mitochondrial bioenergetics (ECAR/OCR), microglial phenotypic markers, plasma injury biomarkers, and histopathology of the lesion. Results: In H₂O₂-challenged BV2 cells, ZnHPB improved viability more effectively than MP, with associated reductions in intracellular ROS, partial restoration of mitochondrial OXPHOS capacity, and alleviation of ferroptosis-related transcriptional signatures (GPX4, ACSL4, COX2). In SCI mice, ZnHPB preserved 86.71% (preventive) and 74.06% (post-injury) of white matter at the lesion epicenter and restored plasma CK, AST, and LDH toward physiological levels. Microglial phenotypic markers shifted from an M1-associated toward an M2-associated phenotype. No visceral toxicity was observed over 60 days. Conclusion: By integrating ferrous-ion sequestration with ROS elimination and mitochondrial support, ZnHPB interrupts the self-perpetuating loop of oxidative stress and neuroinflammation that characterizes secondary SCI pathology. Under the conditions tested, ZnHPB compared favorably with MP across multiple preclinical readouts, supporting further mechanistic and translational evaluation.

Spinal cord injury (SCI) encompasses a series of pathophysiological processes, including inflammation, apoptosis, autophagy, and pyroptosis, leading to an imbalance in the microenvironment.

Macrophage cells are crucial in the inflammatory and proliferative phases of skin injury. The key to skin regeneration lies in controlling the immune response triggered by macrophages. The current treatment methods for skin defects include scar healing, skin grafting surgery, and skin flap repair surgery. The healing time is too long and cannot be cured for a long time, which seriously endangers the health and quality of life of patients. The hydrogel developed by predecessors has promoted the healing of skin defects by providing a moist environment for the wound surface. A hydrogel wound dressing with self-healing and adhesive qualities can offer enhanced protection to the wound and extend the material's lifespan. This study developed a high-adhesion, injectable, and self-healing hydrogel using PVA. The Northern Schisandrin B (NSB) were trapped within PVA hydrogels (PVA.gel). Due to the presence of PVA gel, which provides strong adhesion and anti-inflammatory properties to NSB, it addresses the issue of NSB solution not adhering to the wound surface, thus ensuring continuous action on the wound surface. During in vitro experiments on wound healing, the hydrogel has the ability to adhere to the wound's surface, thereby improving the healing process. The NSB.PVA.gel is capable of persistently suppressing inflammation to manage the inflammatory milieu in long-term wounds, ensuring a seamless shift from the inflammatory stage to the proliferation stage. The NSB.PVA.gel, known for its efficacy, safety, and ease of use, is capable of meeting a variety of clinical requirements.

Excessive accumulations of reactive oxygen species (ROS) and M1 macrophages are closely associated with the complex pathogenesis of spinal cord injury (SCI). Thus, therapeutics that synergistically exert the elimination of ROS and repolarization of pro-inflammation macrophages are gaining increasing notice. We developed a prussian blue-based nanoflower (KPBF) with near-infrared (NIR) photothermal and antioxidant properties. The KPBF's biofunctions were similar to those of other antioxidant enzymes, such as catalase and superoxide dismutase, which are capable of reducing ROS. With NIR irradiation, KPBF efficiently heated the injured spinal cord lesion. By modifying the CKLVFFAED peptide, KPBF remarkably penetrated through the blood-spinal cord barrier (BSCB) into the local lesion. Moreover, KPBF repolarized M1 macrophages and alleviated neuroinflammation in SCI mice. Overall, KPBF presented a universal nanotherapeutic system with immunoregulation and antioxidant activities for acute SCI recovery.

Traumatic spinal cord injury (SCI), often resulting from external physical trauma, initiates a series of complex pathophysiological cascades, with severe cases leading to paralysis and presenting significant clinical challenges. Traditional diagnostic and therapeutic approaches, particularly X-ray imaging, are prevalent in clinical practice, yet the limited efficacy and notable side effects of pharmacological treatments at the injury site continue to pose substantial hurdles. Addressing these challenges, recent advancements have been made in the development of multifunctional nanotechnology and synergistic therapies, enhancing both the efficacy and safety of radiographic techniques. In this context, we have developed an innovative nerve regeneration and neuroprotection nanoplatform utilizing an X-ray-triggered, on-demand RuFe metal-organic framework (P-RuFe) for SCI recovery. This platform is designed to simulate the enzymatic activities of catalase and superoxide dismutase, effectively reducing the production of reactive oxygen species, and to remove free radicals and reactive nitrogen species, thereby protecting cells from oxidative stress-induced damage. In vivo studies have shown that the combination of P-RuFe and X-ray treatment significantly reduces mortality in SCI mouse models and promotes spinal cord repair by inhibiting glial cell proliferation and neuroinflammation. P-RuFe demonstrates excellent potential as a safe, effective scavenger of reactive oxygen and nitrogen species, offering good stability, biocompatibility, and high catalytic activity, and thus holds promise for the treatment of inflammation-related diseases.