Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation

Abstract

Upon the osteoporotic condition, sluggish osteogenesis, excessive bone resorption, and chronic inflammation make the osseointegration of bioinert titanium (Ti) implants with surrounding bone tissues difficult, often lead to prosthesis loosening, bone collapse, and implant failure. In this study, we firstly designed clickable mussel-inspired peptides (DOPA-N3) and grafted them onto the surfaces of Ti materials through robust catechol-TiO 2 coordinative interactions. Then, two dibenzylcyclooctyne (DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain (BMP-2) were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction. We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1. In vitro, the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells (MSCs), and conspicuous immunopolarization-regulation to shift macrophages to alternative (M2) phenotypes and inhibit inflammation, as well as enhancement of osseointegration and mechanical stability in osteoporotic rats. In summary, our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants, which was conducive to the long-term success of Ti implants, especially in the osteoporotic or inflammatory conditions.

Catalase‐Mimetic Artificial Biocatalysts with Ru Catalytic Centers for ROS Elimination and Stem‐Cell Protection

“…Overproduced reactive oxygen species (ROS) in the living system, including hydrogen peroxide (H 2 O 2 ), superoxide anion (•O 2 − ), hydroxyl radical (•OH), and singlet oxygen ( 1 O 2 ), would result in DNA damage, protein denaturation, lipid peroxidation, and inactivation of other biomolecules, causing harmful cellular dysfunction, histological regeneration failure, and even refractory chronic diseases, such as neurotrauma, myocardial infarction, rheumatoid arthritis, bone defects, and diabetic feet. [1][2][3][4][5] To balance the oxidative stress, the living system relied on two types of ROS scavengers: i) antioxidant substances (vitamins, carotenoids, and flavonoids), [6][7][8][9][10] and ii) natural antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). [8,11,12] A variety of antioxidant molecules have been studied; though promising for scavenging ROS in vitro, many reported antioxidant molecules suffer from low treatment efficiencies compared to natural enzymes.…”

Synergetic osteogenesis of extracellular vesicles and loading RGD colonized on 3D-printed titanium implants

“…It is proved that RGD induces adhesion and migration through interaction with integrin protein αvβ3 and enhances the activation of BMPR/Smad signaling pathway to assist osteogenesis. 41 In addition, EVs had been investigated to promote osteogenesis through triggering BMPR/MAPK14 and BMPR/ Smad signaling pathways. 42 According to the outstanding performance on relative gene expression, EVs RGD group proved the synergistic effect of EVs and RGD on inducing osteogenesis by enhancing the activation of the signaling pathway of each other.…”

Microporous structures on mineralized collagen mediate osteogenesis by modulating the osteo-immune response of macrophages

“…The osteoimmune environment plays an essential role in bone repair, most of the repair process promotes the differentiation of osteoblastic cells on the implanted-biomaterial surfaces generated the microenvironment, but the topics about microporous structures-mediated osteogenesis are generally neglected ( Liu, et al, 2010 ; Sussman, et al, 2014 ; Niu, et al, 2020 ; Sun, et al, 2022 ). The presence of microporous structures on the biomaterial surface is crucial for bone formation ( Kang, et al, 2021 ).…”