pH/Temperature Responsive Curcumin-Loaded Micelle Nanoparticles Promote Functional Repair after Spinal Cord Injury in Rats via Modulation of Inflammation.

BACKGROUND: The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration. METHODS: In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso-Beattie-Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining. RESULTS: The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements. CONCLUSION: Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.

Graded-Three-Dimensional Cell-Encapsulating Hydrogel as a Potential Biologic Scaffold for Disc Tissue Engineering.

BACKGROUND: Intervertebral disk (IVD) degeneration, which can cause lower back pain, is a major predisposing factor for disability and can be managed through multiple approaches. However, there is no satisfactory strategy currently available to reconstruct and recover the natural properties of IVDs after degeneration. As tissue engineering develops, scaffolds with embedded cell cultures have proved critical for the successful regeneration of IVDs. METHODS: In this study, an integrated scaffold for IVD replacement was developed. Through scanning electron microscopy and other mechanical measurements, we characterized the physical properties of different hydrogels. In addition, we simulated the physiological structure of natural IVDs. Nucleus pulposus (NP) cells and annulus fibrosus-derived stem cells (AFSCs) were seeded in gelatin methacrylate (GelMA) hydrogel at different concentrations to evaluate cell viability and matrix expression. RESULTS: It was found that different concentrations of GelMA hydrogel can provide a suitable environment for cell survival. However, hydrogels with different mechanical properties influence cell adhesion and extracellular matrix component type I collagen, type II collagen, and aggrecan expression. CONCLUSION: This tissue-engineered IVD implant had a similar structure and function as the native IVD, with the inner area mimicking the NP tissue and the outer area mimicking the stratified annulus fibrosus tissue. The new integrated scaffold demonstrated a good simulation of disc structure. The preparation of efficient and regeneration-promoting tissue-engineered scaffolds is an important issue that needs to be explored in the future. It is hoped that this work will provide new ideas and methods for the further construction of functional tissue replacement discs.

Inflammatory Response to Spinal Cord Injury and Its Treatment.

Spinal cord injury (SCI), as one of the intractable diseases in clinical medicine, affects thousands of human beings, and the pathologic changes after injury have been a hot spot for exploration in clinical medicine. With the development of new treatments, the survival of patients has shown an increasing trend; however, the inflammatory response after injury has not yet been effectively controlled. SCI is divided into primary injury and secondary injury according to the time of injury and pathophysiologic changes. Primary injury occurs immediately and the damage to the injury site is irreversible; however, secondary injury occurs after primary injury and involves pathologic changes at the cellular and molecular levels, which are reversible. Thus, the inflammatory response from secondary injuries has become the main direction of research. In recent years, a complex pathophysiologic mechanism has gradually been unveiled, which has been followed by an upgrade of treatment methods. This article describes the mechanisms of the inflammatory response after SCI and the mainstream treatment modalities. Also, neuroprotective agents and nerve regeneration agent agents are commonly used in the treatment of SCI; the therapeutic mechanism and classification of these agents are reviewed.