In vitro and in vivo biocompatibility assessment of free radical scavenging nanocomposite scaffolds for bone tissue regeneration

Abstract

Bone is the second most transplanted tissue in the world, resulting in increased demand for bone grafts leading to the fabrication of synthetic scaffold grafting alternatives. Fracture sites are under increased oxidative stress after injuries, affecting osteoblast function and hindering fracture healing and remodeling. To counter oxidative stress, free radical scavenging agents, such as cerium oxide nanoparticles, have gained traction in tissue engineering. Toward the goal of developing a functional synthetic system for bone tissue engineering, we characterized the biocompatibility of a porous, bioactive, free radical scavenging nanocomposite scaffold composed of poly (1,8 octanediol-co-citrate), beta-tricalcium phosphate, and cerium oxide nanoparticles. We studied cellular and tissue compatibility utilizing in vitro and in vivo models to assess nanocomposite interactions with both human osteoblast cells and rat subcutaneous tissue. We found the scaffolds were biocompatible in both models and supported cell attachment, proliferation, mineralization, and infiltration. Using hydrogen peroxide, we simulated oxidative stress to study the protective properties of the nanocomposite scaffolds via a reduction in cytotoxicity and recovered mineralization of osteoblast cells in vitro. We also found after implantation in vivo the scaffolds exhibited biocompatible properties essential for successful scaffolds for bone tissue engineering. Cells were able to infiltrate through the scaffolds, the surrounding tissues elicited a minimal immune response, and there were signs of scaffold degradation after 30 days of implantation.After the array of biological characterization, we had confirmed the development of a nanocomposite scaffold system capable of supporting bone-remodeling processes while providing a protective free radical scavenging effect. K E Y W O R D S biocompatibility, cerium, free radical scavenging, human osteoblasts, nanocomposite scaffolds, subcutaneous implant

The Effect of TBB, as an Initiator, on the Biological Compatibility of PMMA/MMA Bone Cement

“…Although radical or non-radical reactive oxygen species (ROS) are important components in various metabolic activities in the human body, they are harmful and trigger inflammatory reactions and functional damages at the cellular and tissue levels [24][25][26], once it is overproduced or when an imbalance between the ROS and antioxidant redox system is triggered. Specifically, free radicals and oxidative stress derived from bone cements lead to a significant reduction in the cell viability, proliferation, differentiation, and mineralization of osteoblasts [25][26][27][28][29][30]. To mitigate this problem, an effective measure was introduced to neutralize free radicals.…”

CeO2 Nanoparticle-Containing Polymers for Biomedical Applications: A Review

“…Bones are the second-most transplanted tissue, after blood transfusion, and an increased demand for bone grafts has led to the mass production of synthetic scaffold alternatives [ 60 ]. To replace bone tissue, rigid porous materials are often used; for example, porous UHMWPE has been used to simulate cancellous tissue [ 6 ].…”

“…Dulany et al developed a functional synthetic 3D scaffold for bone engineering based on (1,8-octanediol-co-citrate), beta-tricalcium phosphate and CeNPs [ 60 ]. They studied cellular and tissue compatibility of the scaffold to assess the interaction of nanocomposites with both human osteoblast cells and rat subcutaneous tissue.…”

“…They also found that, after in vivo implantation, the scaffolds exhibited high biocompatibility required for successful bone engineering. The cells could penetrate the scaffold, the surrounding tissues elicited minimal immune response and, after 30 days of implantation, scaffold degradation was observed [ 60 ].…”

miR-19b enhances osteogenic differentiation of mesenchymal stem cells and promotes fracture healing through the WWP1/Smurf2-mediated KLF5/β-catenin signaling pathway

“…The healing process of bone fractures is widely accepted as a complicated physiological course of events driven by early inflammatory reactions and is accompanied by various biological activities, such as osteogenic differentiation and biomineralization 3 . Fracture sites are commonly subjected to increasing oxidative stress after injuries, which impairs osteoblast function and impedes the process of fracture healing and remodeling 4 . The repair of fracture wounds is critically influenced by mechanical loading as well as the geometric configuration of the fractured fragments 5 .…”