Tailorable hierarchical structures of biomimetic hydroxyapatite micro/nano particles promoting endocytosis and osteogenic differentiation of stem cells

Xu, Dong; Wan, Yuxin; Li, Zhihao; Zou, Qingxia; Du, Chang; Wang, Yingjun

doi:10.1039/d0bm00443j

Cited by 38 publications

(34 citation statements)

References 55 publications

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“…Stimulation of HMSCs by HA raises the activity of the CREB transcription factor, which regulates several osteoblast marker genes. HA nanoparticles can enter the cytoplasm through the endosome and decompose into its ingredients, calcium, and phosphate [47]. Xu et al [47] revealed that increasing the intracellular concentration of calcium ions stimulates several signaling pathways, including calcium, cAMP, Ras, Rap1, and MAPK.…”

Section: Effect Of Hydroxyapatite On Cellular Behaviormentioning

confidence: 99%

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering

Maleki-Ghaleh

Siadati

Fallah

et al. 2021

IJMS

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Bacteria are one of the significant causes of infection in the body after scaffold implantation. Effective use of nanotechnology to overcome this problem is an exciting and practical solution. Nanoparticles can cause bacterial degradation by the electrostatic interaction with receptors and cell walls. Simultaneously, the incorporation of antibacterial materials such as zinc and graphene in nanoparticles can further enhance bacterial degradation. In the present study, zinc-doped hydroxyapatite/graphene was synthesized and characterized as a nanocomposite material possessing both antibacterial and bioactive properties for bone tissue engineering. After synthesizing the zinc-doped hydroxyapatite nanoparticles using a mechanochemical process, they were composited with reduced graphene oxide. The nanoparticles and nanocomposite samples were extensively investigated by transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Their antibacterial behaviors against Escherichia coli and Staphylococcus aureus were studied. The antibacterial properties of hydroxyapatite nanoparticles were found to be improved more than 2.7 and 3.4 times after zinc doping and further compositing with graphene, respectively. In vitro cell assessment was investigated by a cell viability test and alkaline phosphatase activity using mesenchymal stem cells, and the results showed that hydroxyapatite nanoparticles in the culture medium, in addition to non-toxicity, led to enhanced proliferation of bone marrow stem cells. Furthermore, zinc doping in combination with graphene significantly increased alkaline phosphatase activity and proliferation of mesenchymal stem cells. The antibacterial activity along with cell biocompatibility/bioactivity of zinc-doped hydroxyapatite/graphene nanocomposite are the highly desirable and suitable biological properties for bone tissue engineering successfully achieved in this work.

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Section: Effect Of Hydroxyapatite On Cellular Behaviormentioning

confidence: 99%

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering

Maleki-Ghaleh

Siadati

Fallah

et al. 2021

IJMS

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“…Previous papers have typically used nanosize HA particles to fabricate scaffolds for bone tissue engineering. [ 35–39 ] Furthermore, these prior studies mainly focused on scaffold fabrication and in vitro cell response. [ 40–41 ] In addition, researchers have utilized HA in low concentrations in the literature.…”

Section: Introductionmentioning

confidence: 99%

“…Some of the previous studies have used complex processing techniques to synthesize nanoscale HA particles such as nanoflakes and nanorods to evaluate osteogenic differentiation. [ 37–39 ] In our study, commercially available nonprocessed HA microparticles were used at different concentrations within a gelatin‐based hydrogel (GelMA) matrix to increase the mechanical stability of the resulting scaffolds and promote osteogenic differentiation of the preosteoblasts. [ 32–35 ] Our approach is a unique way to achieve highly tunable osteoinductive scaffolds and enables to control the osteogenic differentiation of predifferentiated stem cells.…”

Section: Introductionmentioning

confidence: 99%

Hydroxyapatite‐Incorporated Composite Gels Improve Mechanical Properties and Bioactivity of Bone Scaffolds

Suvarnapathaki

Lantigua

et al. 2020

Macromolecular Bioscience

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require mechanically strong scaffolds to support cell differentiation and mineral deposition. [8-10] The commonly used biomaterials, such as ceramics and metals, are mechanically robust but are compatible with only certain cell cultures. Despite relatively weak mechanical properties, hydrogels exhibit exceptional biomimetic properties and material tunability. [11,12] The spatial and temporal control found in hydrogel synthesis approaches also assists in generating modular mechanical and chemical properties. These aspects enable the generation of scaffolds that mimic the native tissue microenvironment. [13,14] Across all human tissue types, cells are sensitive and responsive to mechanical stresses and stiffnesses, including compression, tension, and shear. [15] Typically, the stiffness of hydrogels can be modified by adjusting the prepolymer concentration and the cross-linking time. [16,17] These techniques can result in stiffer hydrogels but lead to limitations in the biological performance of the material. These limitations have necessitated innovative approaches such as reinforcing hydrogels with nano/microfibers in various weaving patterns. [18,19] Another approach to improve the mechanical and biological properties of hydrogels simultaneously is to process these composite materials at higher cross-linking densities. The mechanical properties have been demonstrated to affect cell migration and tissue morphogenesis within the material. [8] More recently, hydroxyapatite ((HA), Ca 10 (PO 4) 6 (OH) 2), silver, and gold nanoparticles have been incorporated into hydrogels to enhance the scaffold's mechanical capabilities and cytocompatibility. [20,21] In previous works, HA has been used as a filling material to fabricate biocompatible matrices in orthopedic and mineralized implants. [22-24] HA has a natural tendency to bind to osseous tissues and its physical properties are similar to that of the native minerals in the human body. [22,25-29] The success of HApolymer composite materials has offered advanced and desirable qualities in biomimetic and mechanically competent bone tissue engineering scaffolds. [30] In the past, different forms of tissue scaffolds were fabricated using HA, such as electrospun fibers, 3D printed thermoplastic polymers, and freeze-dried matrices. [31-34] In our work, we have generated HA-reinforced, hydrogel-based scaffolds which have high water content and have biomimetic properties. Reinforcing polymeric scaffolds with micro/nanoparticles improve their mechanical properties and render them bioactive. In this study, hydroxyapatite (HA) is incorporated into 5% (w/v) gelatin methacrylate (GelMA) hydrogels at 1, 5, and 20 mg mL −1 concentrations. The material properties of these composite gels are characterized through swelling, degradation, and compression tests. Using 3D cell encapsulation, the cytocompatibility and osteogenic differentiation of preosteoblasts are evaluated to assess the biological properties of the composite scaffolds. The in vitro assays demonstrate increasing cell prolife...

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“…Bone destruction is associated with severely imbalanced bone remodeling, secondary to increased osteoclastogenesis and significant osteoblast suppression, which leads to serious bone loss and cause the stability of titanium plants to be endangered even with a hydroxyapatite coating. [30][31][32] Therefore, it is of great significance to increase the bone induction ability of joint prosthesis by eliminating possible interfering factors for the treatment of orthopedic diseases.…”

Section: Discussionmentioning

confidence: 99%

Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats

Tao

Yang

2021

J Biomater Appl

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Despite advances in the pathogenesis of Tauroursodeoxycholic acid (TUDCA) on bone, the understanding of the effects and mechanisms of bone osseointegration in TUDCA-associated Hydroxyapatite (HA)-coated titanium implants remains poor. Therefore, the present work was aimed to evaluate the effect of local administration with TUDCA on HA-coated titanium implants osseointegration in ovariectomized(OVX) rats and further investigation of the possible mechanism. Twelve weeks after bilateral ovariectomy, all animals were randomly divided into three groups: sham operation(Sham) group, OVX group and TUDCA group, and all the rats from Sham group and OVX group received HA implants and animals belonging to group TUDCA received TUDCA-HA implants until death at 12 weeks. The bilateral femurs of rats were harvested for evaluation. TUDCA increased new bone formation around the surface of titanium rods and push-out force other than group OVX. Histology, Micro-CT and biochemical analysis results showed systemic TUDCA showed positive effects than OVX group on bone formation in osteopenic rats, with beneficial effect on via activation OPG/RANKL pathway and BMP-2/Smad1 pathway and microarchitecture as well as by reducing protein expression of TNF-α and IFN-γ. The present study suggests that local use of TUDCA may bring benefits to the osseointegration of HA-coated titanium implants in patients with osteoporosis, and this effect may be related to the inhibition of inflammatory reaction and promotion of osteogenesis.

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Tailorable hierarchical structures of biomimetic hydroxyapatite micro/nano particles promoting endocytosis and osteogenic differentiation of stem cells

Abstract: Hydroxyapatite (HA) micro/nano particles show great promise as artificial bone and dental substitutes, or drug carrier systems.

Cited by 38 publications

References 55 publications

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering

Hydroxyapatite‐Incorporated Composite Gels Improve Mechanical Properties and Bioactivity of Bone Scaffolds

Local administration with tauroursodeoxycholic acid could improve osseointegration of hydroxyapatite-coated titanium implants in ovariectomized rats

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