Reactive Oxygen Species‐Scavenging Scaffold with Rapamycin for Treatment of Intervertebral Disk Degeneration

Abstract

The chronic inflammatory microenvironment is characterized by the elevated level of reactive oxygen species (ROS). Here, it is hypothesized that developing an ROS‐scavenging scaffold loaded with rapamycin (Rapa@Gel) may offer a new strategy for modulating the local inflammatory microenvironment to improve intervertebral disk tissue regeneration. The therapeutic scaffold consisting of ROS‐degradable hydrogel can be injected into the injured degeneration site of intervertebral disk (IVD) and can release therapeutics in a programmed manner. The ROS scavenged by scaffold reduces the inflammatory responses. It is found that when rats are treated with Rapa@Gel, this results in an increase in the percentage of M2‐like macrophages and a decrease in M1‐like macrophages in the inflammatory environment, respectively. Regeneration of IVD is achieved by Rapa@Gel local treatment, due to the increased M2 macrophages and reduced inflammation. This strategy may be extended to the treatment of many other inflammatory diseases.

Injectable ROS-scavenging hydrogel with MSCs promoted the regeneration of damaged skeletal muscle

“…The ROS-responsive hydrogel was synthesized according to the previous protocol. 12,13 Gel was obtained by crosslinking poly(vinyl alcohol) (PVA) with a ROS-labile linker:…”

“…The recent development of advanced biomaterials including inorganic materials, organic polymers, and their composites has shown great promise for accelerating the regeneration of damaged tissues. 5 , 8 , 12 , 13 Our previous studies revealed that silk fibroin loaded with MSCs promoted wound healing by regulating the polarization of macrophages, 13 and the ROS-scavenging hydrogels containing rapamycin regulated the inflammatory microenvironment of degenerated intervertebral discs and enhanced the regeneration of degenerated intervertebral discs. 12 Here, an in situ ROS scavenging hydrogel containing MSCs was constructed, which could modulate the local inflammatory microenvironment and improve the myogenic differentiation ability of MSCs, thereby promoting the regeneration of skeletal muscle tissue.…”

“… 5 , 8 , 12 , 13 Our previous studies revealed that silk fibroin loaded with MSCs promoted wound healing by regulating the polarization of macrophages, 13 and the ROS-scavenging hydrogels containing rapamycin regulated the inflammatory microenvironment of degenerated intervertebral discs and enhanced the regeneration of degenerated intervertebral discs. 12 Here, an in situ ROS scavenging hydrogel containing MSCs was constructed, which could modulate the local inflammatory microenvironment and improve the myogenic differentiation ability of MSCs, thereby promoting the regeneration of skeletal muscle tissue. In addition, MSCs could regulate the immune response and anti-inflammation effects by the inhibition of activated macrophages and T cells.…”

Implantable blood clot loaded with BMP-2 for regulation of osteoimmunology and enhancement of bone repair

“…Protein expression was analyzed by western blot according to the standard instructions [ 30 ]. MC3T3-E1 cells were treated with PBS, 25 ng BMP-2, 100 μL BC, 100 μL BMP-2@BC containing the same amount of BMP-2 for 24 h. In detail, MC3T3-E1 cells were cultured in the lower compartment and BMP-2@BC were added to the upper compartment in a transwell system.…”

“…The recent development of advanced biomaterials including inorganic materials [ [15] , [16] , [17] ], organic polymers [ [18] , [19] , [20] , [21] , [22] , [23] , [24] ], and their composites [ 25 , 26 ] has shown great promise for accelerating bone reconstruction [ 27 , 28 ], providing alternatives bone remodeling methods [ [29] , [30] , [31] , [32] ]. Despite the outcomes of biomaterials for bone repair, many issues still hinder the clinical transformation from several aspects.…”