Three-dimensional printing of microfiber- reinforced hydrogel loaded with oxymatrine for treating spinal cord injury.

Spinal cord injury (SCI) causes severe neural tissue damage and motor/sensory dysfunction. Since the injured spinal cord tissue has limited self-regeneration ability, several strategies, including cell therapy, drug delivery, and tissue engineering scaffold implantation, have been employed to treat SCI. However, each of these strategies fails to obtain desirable outcomes due to their respective limitations. In comparison, advanced tissue engineering scaffolds with appropriate topographical features, favorable composition, and sustained drug delivery capability can be employed to recruit endogenous neural stem cells (NSCs), induce neuronal differentiation, and facilitate neuron maturation. This can lead to the regeneration of injured spinal cord tissue and the recovery of motor function. In this study, fiber bundle-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with oxymatrine (OMT) were produced through nearfield direct write electrospinning. The spinal cord extracellular matrix-based hydrogel was then coated with OMT. The physical/chemical properties and in vitro degradation behavior of the composite scaffolds were investigated. The in vitro cell culture results showed that composite scaffolds loaded with OMT promoted the differentiation of NSCs into neurons and inhibited differentiation into astrocytes. The in vivo results showed that the composite scaffolds loaded with OMT recruited NSCs from the host tissue, promoted neuronal differentiation and axon extension at the lesion site, inhibited glial scar formation at/around the lesion site, and improved the recovery of motor function in rats with SCI. To sum up, 3D-printed microfiber-reinforced spinal cord extracellular matrix hydrogel scaffolds loaded with OMT are promising biomaterials for the treatment of SCI.

Retraction: Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury.

[This retracts the article DOI: 10.1039/D0RA02661A.].

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

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-ß-cyclodextrin-polyethene glycol diacrylate (designated G-CD-PEGDA) hydrogel, loaded with WAY-316606 to activate canonical Wnt/ß-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.

Acellularized spinal cord scaffolds incorporating bpV(pic)/PLGA microspheres promote axonal regeneration and functional recovery after spinal cord injury.

Spinal cord injury (SCI) is a traumatic injury to the central nervous system (CNS) with a high rate of disability and a low capability of self-recovery. Phosphatase and tensin homolog (PTEN) inhibition by pharmacological blockade with bisperoxovanadium (pic) (bpV(pic)) has been reported to increase AKT/mTOR activity and induce robust axonal elongation and regeneration. However, the therapeutic effect of bpV(pic) in treating SCI is limited due to the lack of efficient delivery approaches. In this study, a composite scaffold consisting of an acellular spinal cord (ASC) scaffold and incorporated bpV(pic) loaded poly (lactic-co-glycolic acid) (PLGA) microspheres was developed, in order to improve the therapeutic effect of bpV(pic) on SCI. The inhibition of PTEN activity and activation of the mTORC1/AKT pathway, the axonal regeneration and the markers of apoptosis were analyzed via western blot and immunofluorescence in vitro. The bpV(pic)/PLGA/ASC scaffolds showed excellent biocompatibility and promoted the viability of neural stem cells and axonal growth in vitro. Implantation of the composite scaffold into rats with hemi-sectioned SCI resulted in increased axonal regeneration and functional recovery in vivo. Besides, bpV(pic) inhibited the phosphorylation of PTEN and activated the PI3K/mTOR signaling pathway. The successful construction of the composite scaffold improves the therapeutic effect of bpV(pic) on SCI.