Ba/Mg co-doped hydroxyapatite/PLGA composites enhance X-ray imaging and bone defect regeneration.

Hydroxyapatite (HA) is the most commonly used orthopedic implant material. In recent years, the emergence of cationic doped hydroxyapatite has revealed more possibilities for the biological application of HA. Conventional HA does not promote new bone formation because of its poor osteoinductive activity, and has a similar density to that of bone, leading to difficulty in distinguishing both via imaging. Magnesium ions are useful for regulating the cellular behavior and promoting bone regeneration. Ba ion related compounds, such as BaSO4, have a strong X-ray shielding effect. In this study, Ba/Mg@HA was synthesized to prepare Ba/Mg@HA/PLGA composites, and we aimed to investigate if Ba/Mg@HA/PLGA composites enhanced bone repair on osteoblasts and tibial defects, as well as the X-ray and CT imaging ability of bone implants in rats. The in vitro experimental results showed that the Ba/Mg@HA/PLGA composites significantly improved the attachment and osteogenic differentiation of MC3T3-E1 cells. These include the promotion of mineral deposition, enhancement of alkaline phosphatase activity, upregulation of OCN and COL-1 gene expression, and increase in COL-1 and OCN protein expression in a time- and concentration-dependent manner. The in vivo experimental results showed that the Ba/Mg@HA/PLGA composites significantly increased the rate of bone defect healing and the expression of BMP-2 and COL-1 in the bones of rats. X-ray and CT imaging results showed that the Ba/Mg@HA/PLGA composites enhanced the X-ray imaging ability. These findings indicate that the Ba/Mg@HA/PLGA composites can effectively promote bone formation and improve the X-ray and CT imaging abilities to a certain extent.

[1]  L. Qin,et al.  Synergistic effects of magnesium ions and simvastatin on attenuation of high-fat diet-induced bone loss , 2021, Bioactive materials.

[2]  Zongliang Wang,et al.  Improved hemostatic effects by Fe3+ modified biomimetic PLLA cotton-like mat via sodium alginate grafted with dopamine , 2021, Bioactive materials.

[3]  Y. Lai,et al.  Hydroxyapatite-modified micro/nanostructured titania surfaces with different crystalline phases for osteoblast regulation , 2020, Bioactive materials.

[4]  P. Chu,et al.  Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification , 2020, Bioactive materials.

[5]  Zongliang Wang,et al.  Gadolinium-Doped BTO-Functionalized Nanocomposites with Enhanced MRI and X-ray Dual Imaging to Simulate the Electrical Properties of Bone. , 2020, ACS applied materials & interfaces.

[6]  Bin Wu,et al.  Impact of structural features of Sr/Fe co-doped HAp on the osteoblast proliferation and osteogenic differentiation for its application as a bone substitute. , 2020, Materials science & engineering. C, Materials for biological applications.

[7]  H. Isaksson,et al.  Longitudinal in vivo monitoring of callus remodelling in BMP-7 and Zoledronate treated fractures. , 2020, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[8]  Akhilesh K Gaharwar,et al.  Inorganic Biomaterials for Regenerative Medicine. , 2020, ACS applied materials & interfaces.

[9]  Zongliang Wang,et al.  Synergistic osteogenesis promoted by magnetically actuated nano-mechanical stimuli. , 2019, Nanoscale.

[10]  Yufeng Zheng,et al.  A functionalized TiO2/Mg2TiO4 nano-layer on biodegradable magnesium implant enables superior bone-implant integration and bacterial disinfection. , 2019, Biomaterials.

[11]  K. Marycz,et al.  Lithium ions (Li+) and nanohydroxyapatite (nHAp) doped with Li+ enhance expression of late osteogenic markers in adipose-derived stem cells. Potential theranostic application of nHAp doped with Li+ and co-doped with europium (III) and samarium (III) ions. , 2019, Materials science & engineering. C, Materials for biological applications.

[12]  Hongwei Lu,et al.  Functionalized cell-free scaffolds for bone defect repair inspired by self-healing of bone fractures: A review and new perspectives. , 2019, Materials science & engineering. C, Materials for biological applications.

[13]  A. Przekora,et al.  The summary of the most important cell-biomaterial interactions that need to be considered during in vitro biocompatibility testing of bone scaffolds for tissue engineering applications. , 2019, Materials science & engineering. C, Materials for biological applications.

[14]  K. Koval,et al.  Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery , 2019, Journal of orthopaedic trauma.

[15]  Pengfei Wei,et al.  Injectable PLGA microspheres with tunable magnesium ion release for promoting bone regeneration. , 2019, Acta biomaterialia.

[16]  Teddy Tite,et al.  Cationic Substitutions in Hydroxyapatite: Current Status of the Derived Biofunctional Effects and Their In Vitro Interrogation Methods , 2018, Materials.

[17]  F. Luyten,et al.  Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. , 2018, Biomaterials.

[18]  N. Samadi,et al.  Biodistribution of strontium and barium in the developing and mature skeleton of rats , 2018, Journal of Bone and Mineral Metabolism.

[19]  I. Pană,et al.  Sputtered Si and Mg doped hydroxyapatite for biomedical applications , 2018, Biomedical materials.

[20]  Huan Zhou,et al.  Magnesium-based bioceramics in orthopedic applications. , 2018, Acta biomaterialia.

[21]  David Holmes Non-union bone fracture: a quicker fix , 2017, Nature.

[22]  K. Yeung,et al.  Bone grafts and biomaterials substitutes for bone defect repair: A review , 2017, Bioactive materials.

[23]  Pardis Moslemzadeh Tehrani,et al.  A top-down approach for the synthesis of nano-sized Ba-doped hydroxyapatite , 2017, Journal of the Australian Ceramic Society.

[24]  P. Messina,et al.  Manipulation of Mg2+-Ca2+ Switch on the Development of Bone Mimetic Hydroxyapatite. , 2017, ACS applied materials & interfaces.

[25]  L. Lidgren,et al.  Nano-Hydroxyapatite Bone Substitute Functionalized with Bone Active Molecules for Enhanced Cranial Bone Regeneration. , 2017, ACS applied materials & interfaces.

[26]  J. Nedelec,et al.  First-Row Transition Metal Doping in Calcium Phosphate Bioceramics: A Detailed Crystallographic Study , 2017, Materials.

[27]  Yufeng Zheng,et al.  Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats , 2016, Nature Medicine.

[28]  Ning Zhang,et al.  In Vivo MRI and X‐Ray Bifunctional Imaging of Polymeric Composite Supplemented with GdPO4·H2O Nanobundles for Tracing Bone Implant and Bone Regeneration , 2016, Advanced healthcare materials.

[29]  Yunfei Xie,et al.  Luminescence Enhanced Eu(3+)/Gd(3+) Co-Doped Hydroxyapatite Nanocrystals as Imaging Agents In Vitro and In Vivo. , 2016, ACS applied materials & interfaces.

[30]  Richard O.C. Oreffo,et al.  Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration. , 2016, Biomaterials.

[31]  M. Ginebra,et al.  Ion-doping as a strategy to modulate hydroxyapatite nanoparticle internalization. , 2016, Nanoscale.

[32]  A. Schilling,et al.  Effects of extracellular magnesium extract on the proliferation and differentiation of human osteoblasts and osteoclasts in coculture. , 2015, Acta biomaterialia.

[33]  Chun Gwon Park,et al.  Bioabsorbable bone fixation plates for X-ray imaging diagnosis by a radiopaque layer of barium sulfate and poly(lactic-co-glycolic acid). , 2015, Journal of biomedical materials research. Part B, Applied biomaterials.

[34]  Haizhu Sun,et al.  Enhanced biocompatibility of PLGA nanofibers with gelatin/nano-hydroxyapatite bone biomimetics incorporation. , 2014, ACS applied materials & interfaces.

[35]  J. Jansen,et al.  Tantalum oxide and barium sulfate as radiopacifiers in injectable calcium phosphate-poly(lactic-co-glycolic acid) cements for monitoring in vivo degradation. , 2014, Journal of biomedical materials research. Part A.

[36]  Xinyuan Zhu,et al.  Wet-chemical synthesis of Mg-doped hydroxyapatite nanoparticles by step reaction and ion exchange processes. , 2013, Journal of materials chemistry. B.

[37]  Chun Gwon Park,et al.  Biodegradable internal fixation plates enabled with X-ray visibility by a radiopaque layer of β-tricalcium phosphate and poly (lactic-co-glycolic acid). , 2013, Journal of biomedical materials research. Part B, Applied biomaterials.

[38]  A. Ghanayem,et al.  A challenge to integrity in spine publications: years of living dangerously with the promotion of bone growth factors. , 2011, The spine journal : official journal of the North American Spine Society.

[39]  Y. Leng,et al.  Synthesis, characterization and ab initio simulation of magnesium-substituted hydroxyapatite. , 2010, Acta biomaterialia.

[40]  M. Gazzano,et al.  Ionic substitutions in calcium phosphates synthesized at low temperature. , 2010, Acta biomaterialia.

[41]  M. Lombardi,et al.  Mg-substituted hydroxyapatite nanopowders: Synthesis, thermal stability and sintering behaviour , 2009 .

[42]  Xuesi Chen,et al.  The nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with L-lactic acid oligomer for bone repair. , 2009, Acta biomaterialia.

[43]  Xuesi Chen,et al.  In vivo mineralization and osteogenesis of nanocomposite scaffold of poly(lactide-co-glycolide) and hydroxyapatite surface-grafted with poly(L-lactide). , 2009, Biomaterials.

[44]  A. Maclean,et al.  Available biological treatments for complex non-unions. , 2007, Injury.