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Cited by 115Bone Tissue Engineering MaterialsMagnesium Alloys: Properties and ApplicationsDental Implant Techniques and Outcomes

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3D-Printed PCL/Zn scaffolds for bone regeneration with a dose-dependent effect on osteogenesis and osteoclastogenesis

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Wang, Siyi, Gu, Ranli, Wang, Feilong, Zhao, Xiao, Yang, Fan, Xu, Yuqian, Yan, Fanyu, Zhu, Yuan, Xia, Dandan, Liu, Yunsong·2022·Materials Today Bio
DOI 10.1016/j.mtbio.2021.100202PMC PMC8753274
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Abstract

Polycaprolactone (PCL) is a polymer material suitable for being prepared into porous scaffolds used in bone tissue engineering, however, insufficient osteogenic ability and mechanical strength limit its application. Zinc (Zn) alloy with proper mechanical strength and osteogenesis is a promising biodegradable metal that have attracted much attention. Herein, we combined the advantages of PCL and Zn by fabricating PCL/Zn composite scaffolds with different Zn powder contents (1 ​wt%, 2 ​wt%, 3 ​wt%) through fused deposition modelling. The ​mechanical property, cytocompatibility and Zn ​ions release ​behavior of PCL/Zn scaffolds were analyzed ​in vitro. The osteogenesis and osteoclastogenesis properties of the scaffolds were evaluated by being implanted into Sprague–Dawley rats calvaria defect. Results showed that the PCL/Zn scaffolds exhibited improved mechanical properties and cytocompatibility compared with the pure PCL scaffolds. At 8 weeks after in vivo implantaion, the addition of Zn powder promoted new bone formation, in a dose-dependent manner. The scaffolds with 2 ​wt% Zn displayed the best osteogenic effect, while the osteogenic effect was slightly reduced in the scaffolds with 3 ​wt% Zn. In the studied Zn contents, the PCL/Zn scaffolds gradually promoted osteoclastogenesis with increasd Zn content. In the 3 ​wt% Zn group, TRAP-positive cells were observed on the newly formed bone edges around the scaffolds. These dose-dependent effects were verified in vitro using MC3T3-E1 and RAW264.7 ​cells. Finally, we revealed that Zn2+ regulated osteogenesis and osteoclastogenesis by activation of the Wnt/β-catenin and NF-κB signalling pathways, respectively.

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Research works printed but not linked: 58

  1. Kneser, 2006, Tissue engineering of bone: the reconstructive surgeon's point of view, J. Cell Mol. Med., 10, 7, 10.1111/j.1582-4934.2006.tb00287.x · DOI
  2. Tang, 2016, Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration, Biomaterials, 83, 363, 10.1016/j.biomaterials.2016.01.024 · DOI · Paper page
  3. Winkler, 2018, A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: the unsolved challenge, Bone Joint Res., 7, 232, 10.1302/2046-3758.73.BJR-2017-0270.R1 · DOI
  4. Pape, 2010, Autologous bone graft: properties and techniques, J Orthop Trauma., 24 Suppl 1, S36, 10.1097/BOT.0b013e3181cec4a1 · DOI
  5. Amini, 2012, Bone tissue engineering: recent advances and challenges, Crit. Rev. Biomed. Eng., 40, 363, 10.1615/CritRevBiomedEng.v40.i5.10 · DOI
  6. Khan, 2005, The biology of bone grafting, J. Am. Acad. Orthop. Surg., 13, 77, 10.5435/00124635-200501000-00010 · DOI
  7. Kashte, 2017, Artificial bone via bone tissue engineering: current scenario and challenges, Tissue Eng. Regen. Med., 14, 1, 10.1007/s13770-016-0001-6 · DOI
  8. Bose, 2012, Recent advances in bone tissue engineering scaffolds, Trends Biotechnol., 30, 546, 10.1016/j.tibtech.2012.07.005 · DOI
  9. Hollister, 2005, Porous scaffold design for tissue engineering, Nat. Mater., 4, 518, 10.1038/nmat1421 · DOI
  10. Liao, 2014, The osteogenesis of bone marrow stem cells on mPEG-PCL-mPEG/hydroxyapatite composite scaffold via solid freeform fabrication, BioMed Res. Int., 2014, 321549, 10.1155/2014/321549 · DOI
  11. Qin, 2019, Additive manufacturing of biodegradable metals: Current research status and future perspectives, Acta Biomater., 98, 3, 10.1016/j.actbio.2019.04.046 · DOI
  12. Roseti, 2017, Scaffolds for bone tissue engineering: state of the art and new perspectives, Mater. Sci. Eng. C Mater. Biol. Appl., 78, 1246, 10.1016/j.msec.2017.05.017 · DOI · Paper page
  13. Babilotte, 2019, 3D printed polymer-mineral composite biomaterials for bone tissue engineering: fabrication and characterization, J. Biomed. Mater. Res. B Appl. Biomater., 107, 2579, 10.1002/jbm.b.34348 · DOI
  14. Kenry, 2018, Recent advances in biodegradable conducting polymers and their biomedical applications, Biomacromolecules, 19, 1783, 10.1021/acs.biomac.8b00275 · DOI
  15. Wang, 2021, The impact of Zn-doped synthetic polymer materials on bone regeneration: a systematic review, Stem Cell Res. Ther., 12, 123, 10.1186/s13287-021-02195-y · DOI
  16. Khoshroo, 2017, Development of 3D PCL microsphere/TiO(2) nanotube composite scaffolds for bone tissue engineering, Mater. Sci. Eng. C Mater. Biol. Appl., 70, 586, 10.1016/j.msec.2016.08.081 · DOI
  17. Kabir, 2021, Recent research and progress of biodegradable zinc alloys and composites for biomedical applications: biomechanical and biocorrosion perspectives, Bioact Mater, 6, 836
  18. Zheng, 2014, Biodegradable metals, Materials Science & Engineering R-Reports, 77, 1, 10.1016/j.mser.2014.01.001 · DOI
  19. Li, 2019, Challenges in the use of zinc and its alloys as biodegradable metals: perspective from biomechanical compatibility, Acta Biomater., 97, 23, 10.1016/j.actbio.2019.07.038 · DOI
  20. Jia, 2020, In vitro and in vivo studies of Zn-Mn biodegradable metals designed for orthopedic applications, Acta Biomater., 108, 358, 10.1016/j.actbio.2020.03.009 · DOI
  21. Xu, 2012, Zn(2+) binding-enabled excited state intramolecular proton transfer: a step toward new near-infrared fluorescent probes for imaging applications, Adv. Health Mater., 1, 485, 10.1002/adhm.201200025 · DOI
  22. Meng, 2019, Effect of zinc substitution in hydroxyapatite coating on osteoblast and osteoclast differentiation under osteoblast/osteoclast co-culture, Regen. Biomater., 6, 349
  23. Tiffany, 2019, The inclusion of zinc into mineralized collagen scaffolds for craniofacial bone repair applications, Acta Biomater., 93, 86, 10.1016/j.actbio.2019.05.031 · DOI
  24. Fu, 2018, Runx2/Osterix and zinc uptake synergize to orchestrate osteogenic differentiation and citrate containing bone apatite formation, Adv. Sci., 5, 1700755, 10.1002/advs.201700755 · DOI
  25. O'Connor, 2020, Zinc as a therapeutic agent in bone regeneration, Materials, 13
  26. Yamada, 2008, Inhibitory effect of Zn2+ in zinc-containing beta-tricalcium phosphate on resorbing activity of mature osteoclasts, J. Biomed. Mater. Res., 84, 344, 10.1002/jbm.a.31265 · DOI
  27. Roy, 2013, Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption, Biomater. Sci., 1, 10.1039/C2BM00012A · DOI
  28. Moonga, 1995, Zinc is a potent inhibitor of osteoclastic bone resorption in vitro, J. Bone Miner. Res., 10, 453, 10.1002/jbmr.5650100317 · DOI
  29. Holloway, 1996, Osteoblast-mediated effects of zinc on isolated rat osteoclasts: inhibition of bone resorption and enhancement of osteoclast number, Bone, 19, 137, 10.1016/8756-3282(96)00141-X · DOI
  30. Liu, 2011, Fabrication and characterization of polycaprolactone/calcium sulfate whisker composites, Express Polym. Lett., 5, 742, 10.3144/expresspolymlett.2011.72 · DOI
  31. Rotbaum, 2019, Quasi-static and dynamic in vitro mechanical response of 3D printed scaffolds with tailored pore size and architectures, Mater Sci Eng C Mater Biol Appl., 96, 176, 10.1016/j.msec.2018.11.019 · DOI
  32. Heydari, 2017, Engineered electrospun polycaprolactone (PCL)/octacalcium phosphate (OCP) scaffold for bone tissue engineering, Mater Sci Eng C Mater Biol Appl., 81, 127, 10.1016/j.msec.2017.07.041 · DOI
  33. Plum, 2010, The essential toxin: impact of zinc on human health, Int. J. Environ. Res. Publ. Health, 7, 1342, 10.3390/ijerph7041342 · DOI · Paper page
  34. Guo, 2020, A pure zinc membrane with degradability and osteogenesis promotion for guided bone regeneration: In vitro and in vivo studies, Acta Biomater, 106, 396, 10.1016/j.actbio.2020.02.024 · DOI
  35. Dong, 2021, 3D-printed Mg-incorporated PCL-based scaffolds: a promising approach for bone healing, Mater. Sci. Eng. C Mater. Biol. Appl., 129, 112372, 10.1016/j.msec.2021.112372 · DOI
  36. Adhikari, 2019, Embedding magnesium metallic particles in polycaprolactone nanofiber mesh improves applicability for biomedical applications, Acta Biomater., 98, 215, 10.1016/j.actbio.2019.04.061 · DOI
  37. Ciardelli, 2005, Blends of poly-(epsilon-caprolactone) and polysaccharides in tissue engineering applications, Biomacromolecules, 6, 1961, 10.1021/bm0500805 · DOI
  38. Zhao, 2020, Fabrication and biological activity of 3D-printed polycaprolactone/magnesium porous scaffolds for critical size bone defect repair, ACS Biomater. Sci. Eng., 6, 5120, 10.1021/acsbiomaterials.9b01911 · DOI
  39. Kang, 2018, Mg-Al and Zn-Al layered double hydroxides promote dynamic expression of marker genes in osteogenic differentiation by modulating mitogen-activated protein kinases, Adv. Health Mater., 7, 10.1002/adhm.201700693 · DOI
  40. Yamaguchi, 2008, Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions, Mol. Cell. Biochem., 312, 157, 10.1007/s11010-008-9731-7 · DOI
  41. Fernandes, 2020, Citrate zinc hydroxyapatite nanorods with enhanced cytocompatibility and osteogenesis for bone regeneration, Mater. Sci. Eng. C Mater. Biol. Appl., 115, 111147, 10.1016/j.msec.2020.111147 · DOI
  42. Levaot, 2018, How cellular Zn(2+) signaling drives physiological functions, Cell Calcium, 75, 53, 10.1016/j.ceca.2018.08.004 · DOI
  43. Togari, 1993, Alteration of in vitro bone metabolism and tooth formation by zinc, Gen. Pharmacol., 24, 1133, 10.1016/0306-3623(93)90360-A · DOI
  44. Lee, 2019, Synergistically enhanced osteoconductivity and anti-inflammation of PLGA/β-TCP/Mg(OH)(2) composite for orthopedic applications, Mater. Sci. Eng. C Mater. Biol. Appl., 94, 65, 10.1016/j.msec.2018.09.011 · DOI
  45. Charles, 2014, Osteoclasts: more than 'bone eaters, Trends Mol. Med., 20, 449, 10.1016/j.molmed.2014.06.001 · DOI · Paper page
  46. Hie, 2011, Zinc deficiency decreases osteoblasts and osteoclasts associated with the reduced expression of Runx2 and RANK, Bone, 49, 1152, 10.1016/j.bone.2011.08.019 · DOI
  47. Hadley, 2010, Dietary zinc reduces osteoclast resorption activities and increases markers of osteoblast differentiation, matrix maturation, and mineralization in the long bones of growing rats, J. Nutr. Biochem., 21, 297, 10.1016/j.jnutbio.2009.01.002 · DOI
  48. Kawamura, 2000, Stimulatory effect of zinc-releasing calcium phosphate implant on bone formation in rabbit femora, J. Biomed. Mater. Res., 50, 184, 10.1002/(SICI)1097-4636(200005)50:2<184::AID-JBM13>3.0.CO;2-3 · DOI
  49. Yamaguchi, 2011, Zinc stimulates osteoblastogenesis and suppresses osteoclastogenesis by antagonizing NF-κB activation, Mol. Cell. Biochem., 355, 179, 10.1007/s11010-011-0852-z · DOI
  50. Hie, 2011, Administration of zinc inhibits osteoclastogenesis through the suppression of RANK expression in bone, Eur. J. Pharmacol., 668, 140, 10.1016/j.ejphar.2011.07.003 · DOI
  51. Houschyar, 2018, Wnt pathway in bone repair and regeneration - what do we know so far, Front. Cell Dev. Biol., 6, 170, 10.3389/fcell.2018.00170 · DOI
  52. Sebastian, 2017, Wnt co-receptors Lrp5 and Lrp6 differentially mediate Wnt3a signaling in osteoblasts, PLoS One, 12, 10.1371/journal.pone.0188264 · DOI
  53. Yan, 2009, Axin2 controls bone remodeling through the beta-catenin-BMP signaling pathway in adult mice, J. Cell Sci., 122, 3566, 10.1242/jcs.051904 · DOI
  54. Cerqueira, 2021, Bioactive zinc-doped sol-gel coating modulates protein adsorption patterns and in vitro cell responses, Mater. Sci. Eng. C Mater. Biol. Appl., 121, 111839, 10.1016/j.msec.2020.111839 · DOI
  55. Guo, 2020, Cordycepin suppresses the migration and invasion of human liver cancer cells by downregulating the expression of CXCR4, Int. J. Mol. Med., 45, 141
  56. Tian, 2019, UCH-L1 mitigates neurotoxicity induced by ZnO particles via stabilizing the inhibitor of NF-kappa B signaling, IκB-α, Ecotoxicol. Environ. Saf., 180, 259, 10.1016/j.ecoenv.2019.03.058 · DOI
  57. Cho, 2020, Evaluation of the antibacterial activity and cell response for 3D-printed polycaprolactone/nanohydroxyapatite scaffold with zinc oxide coating, Polymers, 12, 10.3390/polym12102193 · DOI
  58. Maleki-Ghaleh, 2021, Effect of zinc-doped hydroxyapatite/graphene nanocomposite on the physicochemical properties and osteogenesis differentiation of 3D-printed polycaprolactone scaffolds for bone tissue engineering, Chem. Eng. J., 426, 131321, 10.1016/j.cej.2021.131321 · DOI · Paper page

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Metadata

Authors
Wang, S., Gu, R., Wang, F., Zhao, X., Yang, F., Xu, Y., Yan, F., Zhu, Y., Xia, D., & Liu, Y.
Affiliations
Peking University (CN)
Corresponding author
  • Xia, Dandan
  • Liu, Yunsong
ORCID
Venue
Materials Today Bio
Publisher
Elsevier BV
Published
2022-01
Volume
13
Pages
100202
ISSN
2590-0064 (ISSN-L)
DOI
10.1016/j.mtbio.2021.100202
PMC
PMC8753274
OpenAlex
W4205686195
Cited by
115
References
0
Citations by year
2026: 13 · 2025: 32 · 2024: 38 · 2023: 23 · 2022: 9
FWCI
7.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Materials Today Bio (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Natural Science Foundation of Beijing Municipality (L212014)
  • National Natural Science Foundation of China (81970908, 82170929, 81771039, 51901003)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Physical Sciences › Materials Science › Biomaterials › Magnesium Alloys: Properties and Applications
  • Health Sciences › Dentistry › Oral Surgery › Dental Implant Techniques and Outcomes
Keywords
polycaprolactone, zinc alloys, 3D-printed scaffolds, fused deposition modeling, bone regeneration, bone formation, osteoclastogenesis, zinc ion release, dose-dependent effects, Wnt/β-catenin signaling, NF-κB signaling, calvarial defect, cytocompatibility, mechanical properties

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