TPS-BDNF Hydrogel Promotes Neural Reconnection, Angiogenesis, and Reduces Inflammation After Spinal Cord Injury

Spinal cord injury (SCI) causes severe neurological and physical disabilities, primarily due to the disruption of the local microenvironmental niche. This disruption leads to persistent neuroinflammation, vascular dysfunction, and impaired neuronal regeneration, posing significant challenges for tissue repair. Current standard-of-care often falls short in comprehensively addressing these multifaceted secondary injury mechanisms. Hydrogels offer a versatile strategy for targeted and sustained therapeutic delivery, making them ideal candidates for localized microenvironmental modulation and facilitating niche restoration after SCI.

Researchers developed a bioinspired platform by integrating KTPSLEQRTVYAKGGIKRGK-brain-derived neurotrophic factor mimetic peptides (TPS-BDNF) into a dopamine-modified gelatin methacryloyl (GelMA) hydrogel. This novel GDP hydrogel was designed for minimally invasive delivery and localized microenvironment modulation. In vitro and in vivo studies were conducted to evaluate its properties, including injectability, shear-thinning behavior, and intrinsic antioxidant and anti-inflammatory effects. The primary endpoint was the restoration of the neurovascular niche and subsequent functional recovery after SCI in animal models, with an assessment of neural stem cell mobilization and neuronal differentiation.

The developed TPS-BDNF hydrogel demonstrated several critical properties for SCI repair. It exhibited optimal injectability and shear-thinning behavior, facilitating minimally invasive delivery. Intrinsically, the hydrogel possessed antioxidant and anti-inflammatory properties, crucial for modulating the hostile post-injury microenvironment. The integrated TPS-BDNF component endowed the hydrogel with sustained neurotrophic and pro-angiogenic cues, which are vital for tissue regeneration. This synergistic approach led to significant improvements in the SCI model. The hydrogel promoted the restoration of the neurovascular niche, a key factor for neural survival and integration. Furthermore, it enhanced endogenous neural stem cell mobilization and subsequent neuronal differentiation, contributing to tissue repair. Importantly, the study observed improved functional recovery in SCI animals, suggesting a comprehensive therapeutic effect. The platform also showed minimal systemic toxicity, indicating a favorable safety profile. Overall, the findings highlight the hydrogel's capacity to remodel the lesion microenvironment effectively.

The bioinspired hydrogel synergistically promoted neurogenesis and angiogenesis while delivering strong anti-inflammatory and antioxidant effects, leading to improved functional recovery in SCI animals.