Cerium-doped whitlockite nanohybrid scaffolds promote new bone regeneration via SMAD signaling pathway

Abstract The development of nanoscience, nanohybrid technology and molecular biology provide an important strategy in the construction of novel bone scaffolds. Nanosized whitlockite (WH) and trace cerium (Ce) element exist widely in human bones; however their positive functions on bone cells/tissues still remain unknown. Inspired by the chemical components and nanostructures of bones, Ce-doped WH/chitosan (Ce-WH/CS) nanohybrid scaffolds were developed for new bone regeneration. The Ce-WH/CS scaffolds exhibited interconnected macropores with sizes of ∼300 μm, which facilitated cell adhesion and bone tissue in-growth. Ce-WH nanoparticles with sizes of 10–50 nm were dispersed on macroporous walls. The WH/CS scaffolds with or without doping Ce3+ ions had non-toxicity to human adipose derived stromal cell (hADSCs). Interestingly, the Ce3+ ions in the Ce-WH/CS scaffolds significantly improved osteogenic activity via activated SMAD signaling pathway, and up-regulated the expression of osteogenic-related genes including osteocalcin (OCN), osterix (OSX) and collagen 1A1 (COL1A1). Rat cranial defect models further demonstrated that Ce-WH/CS scaffolds remarkably accelerated material biodegradation and bone tissue growth compared to WH/CS scaffolds. The exciting finding revealed the positive functions of Ce-WH nanoparticles on bone tissues, and provided a promising platform for new bone regeneration.

• Publication year

  2019

• Venue

  Chemical Engineering Journal

• Publication date

  2019-03-01

• Fields of study

  Medicine, Materials Science, Chemistry, Engineering

• Identifiers
  DOI 10.1016/J.CEJ.2018.11.116
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• A WNT protein therapeutic improves the bone-forming capacity of autografts from aged animals

  2018cited by this paper
• Ligand density-dependent influence of arginine–glycine–aspartate functionalized gold nanoparticles on osteogenic and adipogenic differentiation of mesenchymal stem cells

  2018cited by this paper
• Design and Fabrication of a Hierarchically Structured Scaffold for Tendon‐to‐Bone Repair

  2018cited by this paper
• 3D printing of ceramic-based scaffolds for bone tissue engineering: an overview.

  2018cited by this paper
• Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells.

  2018cited by this paper
• Ice‐Templated Protein Nanoridges Induce Bone Tissue Formation

  2017cited by this paper
• Nacre Topography Produces Higher Crystallinity in Bone than Chemically Induced Osteogenesis.

  2017cited by this paper
• Polylactic Acid Nanofiber Scaffold Decorated with Chitosan Islandlike Topography for Bone Tissue Engineering.

  2017cited by this paper
• Poly (fumaroyl bioxirane) maleate: A potential functional scaffold for bone regeneration.

  2017cited by this paper
• Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering.

  2017cited by this paper
• The Effects of Cerium Oxide Incorporation in Calcium Silicate Coating on Bone Mesenchymal Stem Cell and Macrophage Responses

  2017cited by this paper
• Biomimetic whitlockite inorganic nanoparticles-mediated in situ remodeling and rapid bone regeneration.

  2017cited by this paper
• Ionic Colloidal Molding as a Biomimetic Scaffolding Strategy for Uniform Bone Tissue Regeneration

  2017cited by this paper
• Hierarchically Staggered Nanostructure of Mineralized Collagen as a Bone‐Grafting Scaffold

  2016cited by this paper
• Three-dimensional printing of tricalcium silicate/mesoporous bioactive glass cement scaffolds for bone regeneration.

  2016cited by this paper
• Multifunctional mesoporous bioactive glass/upconversion nanoparticle nanocomposites with strong red emission to monitor drug delivery and stimulate osteogenic differentiation of stem cells

  2016cited by this paper
• Magnesium whitlockite hollow microspheres: a comparison of microwave-hydrothermal and conventional hydrothermal syntheses using fructose 1,6-bisphosphate, and application in protein adsorption

  2016cited by this paper
• TGF-β Signaling Regulates Cementum Formation through Osterix Expression

  2016cited by this paper
• Cerium Oxide Nanoparticle Modified Scaffold Interface Enhances Vascularization of Bone Grafts by Activating Calcium Channel of Mesenchymal Stem Cells.

  2016cited by this paper
• In Vitro and In Vivo Evaluation of Whitlockite Biocompatibility: Comparative Study with Hydroxyapatite and β‐Tricalcium Phosphate

  2016cited by this paper
• Health effects and toxicity mechanisms of rare earth elements-Knowledge gaps and research prospects.

  2015cited by this paper
• Three-dimensional printing of cerium-incorporated mesoporous calcium-silicate scaffolds for bone repair

  2015cited by this paper
• Biocompatibility evaluation of porous ceria foams for orthopedic tissue engineering.

  2015cited by this paper
• pH-Dependent Activity of Dextran-Coated Cerium Oxide Nanoparticles on Prohibiting Osteosarcoma Cell Proliferation.

  2015cited by this paper
• Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.

  2015cited by this paper
• Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects.

  2015cited by this paper
• Fabrication of a chitosan/bioglass three-dimensional porous scaffold for bone tissue engineering applications.

  2014cited by this paper
• Revisiting whitlockite, the second most abundant biomineral in bone: nanocrystal synthesis in physiologically relevant conditions and biocompatibility evaluation.

  2014cited by this paper
• Growth factors in orthopaedic surgery: demineralized bone matrix versus recombinant bone morphogenetic proteins

  2014cited by this paper
• Multidirectional effects of Sr-, Mg-, and Si-containing bioceramic coatings with high bonding strength on inflammation, osteoclastogenesis, and osteogenesis.

  2014cited by this paper
• Synthesis and characterization of CeO2-incorporated mesoporous calcium-silicate materials

  2014cited by this paper
• Hydrothermal fabrication of magnetic mesoporous carbonated hydroxyapatite microspheres: biocompatibility, osteoinductivity, drug delivery property and bactericidal property.

  2014cited by this paper
• Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration.

  2014cited by this paper
• Mitogen-activated protein kinase pathways in osteoblasts.

  2013cited by this paper
• Cellular interaction and toxicity depend on physicochemical properties and surface modification of redox-active nanomaterials.

  2013cited by this paper
• TGF‐β/BMP signaling pathway is involved in cerium‐promoted osteogenic differentiation of mesenchymal stem cells

  2013cited by this paper
• Osseointegration: the slow delivery of BMP-2 enhances osteoinductivity.

  2012cited by this paper
• A prospective, randomised, controlled trial using a Mg-hydroxyapatite - demineralized bone matrix nanocomposite in tibial osteotomy.

  2012cited by this paper
• Development of silk-based scaffolds for tissue engineering of bone from human adipose-derived stem cells.

  2012cited by this paper
• Accumulation of rare earth elements in human bone within the lifespan.

  2011cited by this paper
• Characteristic molar ratios of magnesium, carbon dioxide, calcium and phosphorus in the mineralizing fracture callus and predentine

  2006cited by this paper
• Bone recognition mechanism of porcine osteocalcin from crystal structure

  2003cited by this paper

• Unlocking Advanced Tissue Repair: Engineering PVDF/PCL/WH Membranes with Enhanced Electromechanical and Biological Properties

  2026cites this paper
• Functional poly(ether-ketone-ketone) composite scaffold with enhanced cell-material interaction, anti-inflammatory and osteogenesis for facilitating osteointegration and bone regeneration

  2025cites this paper
• Immune regulative GelMA&Zn2+/Ce3+-whitlockite scaffolds with continuous ions release for bone regeneration

  2025cites this paper
• Carbon quantum dots promote macrophage M2 polarization for bone defect repair

  2025cites this paper
• Whitlockite nanoparticles: A multifaceted magnesium calcium phosphate ceramic.

  2025cites this paper
• Effect of Ce4+ on the Osteogenic Activity of Ce‐Doped Magnesium Phosphate Composite Materials in Repairing Bone Defects

  2025cites this paper
• Whitlockite as a next-generation biomaterial for bone regeneration: A systematic review of In Vivo evidence for bone regeneration

  2025cites this paper
• Fabrication and characterizations of 3D printed GelMA-Gel/bioactive glass scaffolds containing cerium for bone damage repair

  2025cites this paper
• The role and importance of rare earth elements as dopants for hydroxyapatite structure: a comprehensive review

  2025cites this paper
• Manganese-doped oleic acid functionalized whitlockite/polycaprolactone nanocomposite scaffolds enhance bone regeneration through improved dispersibility and antioxidative capacity

  2025cites this paper
• 3D printed composite scaffold accelerates bone regeneration by modulating immunity and promoting angiogenesis

  2025cites this paper
• Impact of Cerium Doping on the Osteogenic Properties of a 3D Biomimetic Piezoelectric Scaffold with Sustained Mg2+ Release

  2025cites this paper
• Physicochemical characterization and effects of monetite obtained from titania-reinforced eggshell on bone repair: a new possibility for tissue bioengineering?

  2025cites this paper
• Flexibility, Photothermal Property, Antibacterial Ability, and Mineralization Activity of Cu/Mn-Doped Inorganic Nanofibers.

  2025cites this paper
• Structural, chemical and biological properties of SiO2-CaO-Er2O3 flexible ceramic nanofibers for biomedical applications

  2024cites this paper
• Cerium-doped calcium phosphate materials for bone tissue engineering

  2024cites this paper
• All-Natural Ceramic Whitlockite/Wollastonite Fiber Composite Bone Scaffolds: DLP Additive Manufacturing, Microstructure, and Performance

  2024cites this paper
• A ceria/calcium-phosphate functional composite coating on magnesium alloy for enhanced adhesion strength, corrosion resistance, and biocompatibility

  2024cites this paper
• All-in-one strategy to develop a near-infrared triggered multifunctional bioactive magnesium phosphate bone cement for bone repair.

  2024cites this paper
• Low-Temperature Aqueous Synthesis and Biocompatibility of Manganese Whitlockite

  2024cites this paper
• An Antibacterial Bionic Periosteum with Angiogenesis-Neurogenesis Coupling Effect for Bone Regeneration.

  2024cites this paper
• Electrophoretic deposition of tea tree oil containing chitosan/gelatin/whitlockite composite coatings for biofilm protection and bone tissue regeneration

  2024cites this paper
• Preparation and physicochemical characterization of whitlockite/PVA/Gelatin composite for bone tissue regeneration

  2024cites this paper
• Carbon capture from low CO2 concentration stream through ternary alkali metal nitrates promotion of MgO sorbents at intermediate temperature and low space velocity

  2024cites this paper
• Effect of strontium and iron on the structural integrity and drug delivery of Whitlockite

  2023cites this paper
• Dependence of Antimicrobial Properties on Site-Selective Arrangement and Concentration of Bioactive Cu2+ Ions in Tricalcium Phosphate

  2023cites this paper
• Gadolinium-doped whitlockite/chitosan composite scaffolds with osteogenic activity for bone defect treatment: In vitro and in vivo evaluations

  2023cites this paper
• The Delivery and Activation of Growth Factors Using Nanomaterials for Bone Repair

  2023cites this paper
• Protective nature of cerium-based oxides coating against Mg corrosion in Hanks’ balanced salt solution

  2023cites this paper
• Photoluminescence, structural and antibacterial properties of co-doped β-Ca3(PO4)2-type phosphates Ca8CuRE(PO4)7 (RE = Eu–Er)

  2023cites this paper
• DNA aptamer functionalized monodisperse Eu/Mn-WH nanoparticle for in vivo magnetic resonance and fluorescence imaging

  2023cites this paper
• 3D printed bioabsorbable composite scaffolds of poly (lactic acid)-tricalcium phosphate-ceria with osteogenic property for bone regeneration

  2023cites this paper
• Experimental characterization and theoretical investigation of Ce/Yb co-doped hydroxyapatites

  2022cites this paper
• Dopamine and DNA functionalized manganese whitlockite nanocrystals for magnetic resonance imaging and chemo-photothermal therapy of tumors.

  2022cites this paper
• Development of osteon-like scaffold-cell construct by quadruple coaxial extrusion-based 3D bioprinting of nanocomposite hydrogel.

  2022cites this paper
• Design strategies for composite matrix and multifunctional polymeric scaffolds with enhanced bioactivity for bone tissue engineering

  2022cites this paper
• A biomimetic piezoelectric scaffold with sustained Mg2+ release promotes neurogenic and angiogenic differentiation for enhanced bone regeneration.

  2022cites this paper
• Highly resilient porous polyurethane composite scaffolds filled with whitlockite for bone tissue engineering

  2022cites this paper
• Effect of chitosan/inorganic nanomaterial scaffolds on bone regeneration and related influencing factors in animal models: A systematic review

  2022cites this paper
• Incorporation of cerium oxide into hydroxyapatite/chitosan composite scaffolds for bone repair

  2022influential citation
• Effect of silicon or cerium doping on the anti-inflammatory activity of biphasic calcium phosphate scaffolds for bone regeneration

  2022cites this paper
• Optimized osteogenesis of biological hydroxyapatite-based bone grafting materials by ion doping and osteoimmunomodulation

  2022cites this paper
• A scaffold with zinc-whitlockite nanoparticles accelerates bone reconstruction by promoting bone differentiation and angiogenesis

  2022cites this paper
• Synthesis of whitlockite nanopowders with different magnesium content

  2022cites this paper
• The role of rare earth elements in bone tissue engineering scaffolds - A review

  2022cites this paper
• Rare earth-based materials for bone regeneration: Breakthroughs and advantages

  2022cites this paper
• Biphasic CK2.1-coated β-glycerophosphate chitosan/LL37-modified layered double hydroxide chitosan composite scaffolds enhance coordinated hyaline cartilage and subchondral bone regeneration

  2021cites this paper
• Incorporation of cerium oxide into zirconia toughened alumina ceramic promotes osteogenic differentiation and osseointegration

  2021cites this paper
• Eu3+/Tb3+-doped whitlockite nanocrystals: Controllable synthesis, cell imaging, and the degradation process in the bone reconstruction

  2021cites this paper
• Facile Polyphenol–Europium Assembly Enabled Functional Poly(l‐Lactic Acid) Nanofiber Mats with Enhanced Antioxidation and Angiogenesis for Accelerated Wound Healing

  2021cites this paper
• Bone whitlockite: synthesis, applications, and future prospects

  2021cites this paper
• Macroporous scaffolds developed from CaSiO3 nanofibers regulating bone regeneration via controlled calcination.

  2020cites this paper
• Surface charge-dependent osteogenic behaviors of edge-functionalized graphene quantum dots

  2020cites this paper
• Synthesis, Characterization and Process Optimization of Bone Whitlockite

  2020cites this paper
• β-Tricalcium Phosphate for Bone Substitution: Synthesis and Properties.

  2020cites this paper
• Mineralization of ytterbium-doped hydroxyapatite nanorod arrays in magnetic chitosan scaffolds improves osteogenic and angiogenic abilities for bone defect healing

  2020cites this paper
• Development of Composite Scaffolds Based on Cerium Doped-Hydroxyapatite and Natural Gums—Biological and Mechanical Properties

  2019cites this paper
• La-Doped biomimetic scaffolds facilitate bone remodelling by synchronizing osteointegration and phagocytic activity of macrophages

  2019cites this paper
• Incorporation of cerium oxide in hollow mesoporous bioglass scaffolds for enhanced bone regeneration by activating the ERK signaling pathway

  2019cites this paper
• Surface treatments on titanium implants via nanostructured ceria for antibacterial and anti-inflammatory capabilitiess.

  2019cites this paper