Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury

by Selleckchem | Oct 21 2023

Spinal cord injury (SCI) is an overwhelming and incurable disabling condition, for which increasing forms of multifunctional biomaterials are being tested, but with limited progression. The promising material should be able to fill SCI-induced cavities and direct the growth of new neurons, with effective drug loading to improve the local micro-organism environment and promote neural tissue regeneration. In this study, a double crosslinked biomimetic composite hydrogel comprised of acellularized spinal cord matrix (ASCM) and gelatin-acrylated-β-cyclodextrin-polyethene glycol diacrylate (designated G-CD-PEGDA) hydrogel, loaded with WAY-316606 to activate canonical Wnt/β-catenin signaling, and reinforced by a bundle of three-dimensionally printed aligned polycaprolactone (PCL) microfibers, was constructed. The G-CD-PEGDA component endowed the composite hydrogel with a dynamic structure with a self-healing capability which enabled cell migration, while the ASCM component promoted neural cell affinity and proliferation. The diffusion of WAY-316606 could recruit endogenous neural stem cells and improve neuronal differentiation. The aligned PCL microfibers guided neurite elongation in the longitudinal direction. Animal behavior studies further showed that the composite hydrogel could significantly recover the motor function of rats after SCI. This study provides a proficient approach to produce a multifunctional system with desirable physiological, chemical, and topographical cues for treating patients with SCI.

Comments:

The study you described presents a novel approach for the treatment of spinal cord injury (SCI) using a multifunctional biomaterial system. The system is designed to address the challenges associated with SCI, including the need to fill cavities, promote neural tissue regeneration, and provide a favorable microenvironment for cell growth and differentiation.

The composite hydrogel used in this study consists of two main components: acellularized spinal cord matrix (ASCM) and gelatin-acrylated-β-cyclodextrin-polyethylene glycol diacrylate (G-CD-PEGDA) hydrogel. The ASCM component, derived from spinal cord tissue, promotes neural cell affinity and proliferation, while the G-CD-PEGDA component provides a dynamic structure with self-healing capabilities, enabling cell migration.

In addition to the hydrogel, the system includes a drug called WAY-316606, which activates the canonical Wnt/β-catenin signaling pathway. This pathway plays a crucial role in neural development and regeneration. The inclusion of WAY-316606 in the hydrogel promotes the recruitment of endogenous neural stem cells and enhances neuronal differentiation.

To further enhance the structural support and guidance for neural regeneration, a bundle of three-dimensionally printed aligned polycaprolactone (PCL) microfibers is incorporated into the composite hydrogel. These microfibers help guide the elongation of neurites, providing a physical scaffold for regenerating neurons to grow in the longitudinal direction.

The researchers conducted animal behavior studies to evaluate the efficacy of the composite hydrogel system. The results showed that the system significantly improved the motor function of rats with SCI, indicating its potential for functional recovery.

Overall, this study demonstrates a promising approach for treating SCI using a multifunctional biomaterial system. The combination of the ASCM and G-CD-PEGDA hydrogel components, along with drug loading and the addition of aligned PCL microfibers, provides a comprehensive set of cues for neural tissue regeneration. Further research and development are needed to translate these findings into clinical applications for the treatment of SCI in humans.