Surface Functionalization of Hydroxyapatite Scaffolds with MgAlEu‐LDH Nanosheets for High‐Performance Bone Regeneration

Abstract

Although artificial bone repair scaffolds, such as titanium alloy, bioactive glass, and hydroxyapatite (HAp), have been widely used for treatment of large-size bone defects or serious bone destruction, they normally exhibit unsatisfied bone repair efficiency because of their weak osteogenic and angiogenesis performance as well as poor cell crawling and adhesion properties. Herein, the surface functionalization of MgAlEu-layered double hydroxide (MAE-LDH) nanosheets on porous HAp scaffolds is reported as a simple and effective strategy to prepare HAp/MAE-LDH scaffolds for enhanced bone regeneration. The surface functionalization of MAE-LDHs on the porous HAp scaffold can significantly improve its surface roughness, specific surface, and hydrophilicity, thus effectively boosting the cells adhesion and osteogenic differentiation. Importantly, the MAE-LDHs grown on HAp scaffolds enable the sustained release of Mg 2+ and Eu 3+ ions for efficient bone repair and vascular regeneration. In vitro experiments suggest that the HAp/MAE-LDH scaffold presents much enhanced osteogenesis and angiogenesis properties in comparison with the pristine HAp scaffold. In vivo assays further reveal that the new bone mass and mineral density of HAp/MAE-LDH scaffold increased by 3.18-and 2.21-fold, respectively, than that of pristine HAp scaffold. The transcriptome sequencing analysis reveals that the HAp/MAE-LDH scaffold can activate the Wnt/𝜷-catenin signaling pathway to promote the osteogenic and angiogenic abilities.

A Recombinant Parathyroid Hormone‐Related Peptide Locally Applied in Osteoporotic Bone Defect

“…To achieve effective bone regeneration repair, bioactive scaffolds for bone regeneration should be non‐toxic or minimally toxic and exhibit good cytocompatibility, which is a fundamental prerequisite for bone regeneration. [ 24 ] This study employed as model cells the MC3T3‐E1 cells, which have been widely used in experimental studies for cytotoxicity evaluation, osteoblast differentiation, in vitro mineralization, and osteoblast mechanisms because of their stable and reproducible properties. [ 25 ] To evaluate the in vitro cytocompatibility of these scaffolds, MC3T3‐E1 cells were inoculated onto these scaffolds and co‐cultured for 3 days before live/dead staining was performed.…”

Hydrophilic surface-modified 3D printed flexible scaffolds with high ceramic particle concentrations for immunopolarization-regulation and bone regeneration

“…50,51 Several investigations have revealed that altering the material surface hydrophilicity via various techniques activates the Wnt/β-catenin pathway and promotes osteogenesis. 39,52 It has also been demonstrated that activating the Wnt/β-catenin pathway leads to macrophage polarization towards the M2 phenotype. 53 We were curious whether alkali-treated 3D-printed scaffolds would affect osteogenesis by activating this signalling pathway, and thus β-catenin protein IHC staining was performed.…”

Layered Double Hydroxides: A Novel Promising 2D Nanomaterial for Bone Diseases Treatment

“…[160] Moreover, the upregulation of Wnt/𝛽-catenin pathway, MAPK-dependent pathway as well as downregulation of NF-𝜅B signaling pathway leading to enhanced osteoblastogenesis and inhibited osteoclastogenesis were reported to contribute to the potent osteogenesis properties of LDHs nanosheets (Figure 6c,d). [35,36,39,118,161,162] Meanwhile, Zhu et al [133] found MgAl-LDH could induce migration, neural differentiation, L-Ca 2+ channel activation, and inducible action potential generation of neural stem cells (NSCs) by activating transforming growth factor-𝛽 receptor 2 (TGFBR2) (Figure 6e). Fernandes et al demonstrated that cytoskeleton rearrangement, extracellular matrix (ECM) remodeling, and inflammatory landscape may account for the LDHs-induced adhesion, proliferation, and migration of fibroblasts, among which many bioactive factors and signal pathways were mobilized.…”