Nanozyme-reinforced hydrogel as a H2O2-driven oxygenerator for enhancing prosthetic interface osseointegration in rheumatoid arthritis therapy

Abstract

Stem cell-based therapy has drawn attention for enhancing the osseointegration efficiency after joint replacement in the rheumatoid arthritis (RA). However, therapeutic efficacy of this approach is threatened by the accumulated reactive oxygen species (ROS) and poor oxygen supply. Herein, we develop a nanozyme-reinforced hydrogel for reshaping the hostile RA microenvironment and improving prosthetic interface osseointegration. The engineered hydrogel not only scavenges endogenously over-expressed ROS, but also synergistically produces dissolved oxygen. Such performance enables the hydrogel to be utilized as an injectable delivery vehicle of bone marrow-derived mesenchymal stem cells (BMSCs) to protect implanted cells from ROS and hypoxia-mediated death and osteogenic limitation. This nanozyme-reinforced hydrogel encapsulated with BMSCs can alleviate the symptoms of RA, including suppression of local inflammatory cytokines and improvement of osseointegration. This work provides a strategy for solving the long-lasting challenge of stem cell transplantation and revolutionizes conventional intervention methods for improving prosthetic interface osseointegration in RA.

Hmga1‐overexpressing lentivirus protects against osteoporosis by activating the Wnt/β‐catenin pathway in the osteogenic differentiation of BMSCs

“…[35][36][37][38] Wnt/β-catenin signaling pathway participates in the regulation of osteogenic differentiation of BMSCs, bone formation, and bone metabolism. 39,40 Activation of the Wnt/β-catenin pathway prevents βcatenin phosphorylation, resulting in the accumulation of βcatenin in the cytoplasm and its translocation into the nucleus where it binds to T-cell factor (TCF)/lymphoid enhancer factor (LEF) to activate transcription of target genes involved in bone formation. 15 It has been reported that Hmga1 amplifies Wnt/β-catenin signaling to enhance selfrenewal and expand the intestinal stem cell compartment.…”

Optimization strategies of mesenchymal stem cell-based therapy for acute kidney injury

“…To address these drawbacks, a beneficial 3D microenvironment is necessary to be designed to bridge the gap between the traditional culture system and the complex architecture in vivo. In addition, it is also worth noting that 3D approaches have become a frontier in stem cell delivery by virtue of their superior capability of promoting the survival and function of the transplanted cells [ 49 ]. Various methods have been developed to meet the demand for 3D cell culture and delivery over recent years.…”

Bone regeneration strategies based on organelle homeostasis of mesenchymal stem cells

“…Thus, Ce and Sr ions could be used to synergistically mediate the recovery of mitochondrial dynamics in MSCs to restore function and enhance osteogenesis (102,103). On this basis, a new strategy based on Mn atom substitution is reported in a recent study for the development of high-performance ROS scavengers with fast enzyme-like catalytic kinetics (104,105). Among various metal oxides, Co 3 O 4 is considered as one of the most promising candidates for catalytic ROS scavenging due to its high redox potential of Co 3+ /Co 2+ (106,107).…”