Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment

Abstract

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain. Although IVDD cannot directly cause death, it can cause pain, psychological burdens, and economic burdens to patients. Current conservative treatments for IVDD can relieve pain but cannot reverse the disease. Patients who cannot tolerate pain usually resort to a strategy of surgical resection of the degenerated disc. However, the surgical removal of IVDD can affect the stability of adjacent discs. Furthermore, the probability of the reherniation of the intervertebral disc (IVD) after surgery is as high as 21.2%. Strategies based on tissue engineering to deliver stem cells for the regeneration of nucleus purposes (NP) and annulus fibrosus (AF) have been extensively studied. The developed biomaterials not only locally withstand the pressure of the IVD but also lay the foundation for the survival of stem cells. However, the structure of IVDs does not provide sufficient nutrients for delivered stem cells. The role of immune mechanisms in IVDD has recently become clear. In IVDD, the IVD that was originally in immune privilege prevents the attack of immune cells (mainly effector T cells and macrophages) and aggravates the disease. Immune regulatory and inflammatory factors released by effector T cells, macrophages, and the IVD further aggravate IVDD. Reversing IVDD by regulating the inflammatory microenvironment is a potential approach for the treatment of the disease. However, the biological factors modulating the inflammatory microenvironment easily degrade in vivo. It makes it possible for different biomaterials to modulate the inflammatory microenvironment to repair IVDD. In this review, we have discussed the structures of IVDs and the immune mechanisms underlying IVDD. We have described the immune mechanisms elicited by different biological factors, including tumor necrosis factors, interleukins, transforming growth factors, hypoxia-inducible factors, and reactive oxygen species in IVDs. Finally, we have discussed the biomaterials used to modulate the inflammatory microenvironment to repair IVDD and their development.

Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus

“…Previous studies have shown that exogenous ROS can induce apoptosis, necrosis, autophagy, and ferroptosis in NPCs [ 30 , 31 , 32 ]. To investigate the involvement of these pathways induced in NPCs by TBHP treatment, we utilized various inhibitors, including Z-VAD (a caspase-dependent apoptosis inhibitor), Necrostatin-1 (Nec-1; a necrosis inhibitor), 3-Methyladenine (3-MA; an autophagy inhibitor), Ferrostatin-1 (Fer-1; a ferroptosis inhibitor), and N-Acetyl-L-cysteine (NAC; an ROS inhibitor).…”

Current status and development direction of immunomodulatory therapy for intervertebral disk degeneration

“…Therefore, we will explore the molecular mechanisms of macrophage polarization to study IVDD in the future. Although tissue engineering scaffolding materials have the potential to modulate the IVD inflammatory microenvironment for the treatment of IVDD, we must note that most IVDD studies simulate the condition in vitro , and there is a lack of in vivo studies of large animals similar to humans ( 147 ). Moreover, the selection of suitable donor cells should enable survival and function in unfavorable inflammatory microenvironments.…”

“…Gene therapy involves the insertion of exogenous genes into appropriate recipient cells of IVDD patients via vectors, which provide sustained therapeutic effects once gene transfer is successful ( 148 ). Essential vectors contribute to translocation into the nucleus and the expression of transgenes, including AAV and RNAi ( 147 ). Among them, AAV has attracted much interest from researchers.…”

Engineered nanomaterials enhance drug delivery strategies for the treatment of osteosarcoma

“…However, the low bioavailability and low solubility of ABZ limit its clinical application ( García et al, 2014 ). Poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) have been widely used in nanomedicine and regenerative medicine due to their biocompatibility ( Xia et al, 2022b ; Xia et al, 2023 ). Zhao et al (2023a) fabricated AD@PLGA-PEG NPs with PLGA–PEG loads ABZ and DOX (ABZ and DOX molar ratio of 4:1) ( Figure 2A ).…”