ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis

Abstract

Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.

Potential Role of Hydrogels in Stem Cell Culture and Hepatocyte Differentiation

“…Recent researchers have observed that stem cells cultured with more hydrophilic materials in a 3D environment could reduce differentiation. They found that hydrophobic materials produced excessive levels of reactive oxygen species (ROS), which can trigger cell differentiation [64,65]. Based on this view, Bai et al [66] fabricated a zwitterionic poly(carboxybetaine)based hydrogel (ZTG) using a specifically selected metalloproteinase-cleavable zwitterionic peptide to reversibly crosslink the gels.…”

Biomaterials-Based Antioxidant Strategies for the Treatment of Oxidative Stress Diseases

“…Ding et al developed a ROS-scavenging hydrogel by crosslinking EGCG, 3-acrylamido phenylboronic acid and acrylamide, and encapsulated bone marrow MSCs within it. The hydrogel effectively enhanced osteointegration of 3D-printed microporous titanium alloy prostheses in an osteoporotic rabbit model, exhibiting the ability to scavenge accumulated ROS, suppress inflammatory cytokine expression and improve osteogenesis-associated markers [219]. Melatonin has been shown to possess free-radical scavenging and antioxidant properties, complementing its crucial role in bone formation [220].…”

The recent progress of endocrine therapy-induced osteoporosis in estrogen-positive breast cancer therapy

“…Under normal physiological conditions, ROS produced by OCs stimulate and promote bone tissue absorption (48). However, deficiency of the potent antioxidant estrogen leads to the accumulation of ROS in the body which in turn affects osteogenic differentiation of stem cells and the formation of osteoporosis (49).…”