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RESEARCH ARTICLE

3D-Printed mesoporous bioglass/ polycaprolactone scaffolds induce macrophage polarization toward M2 phenotype and immunomodulates osteogenic differentiation of BMSCs

Weihua Huang1,2,3,4 ,  Shuai Huang1 ,  Xitao Linghu3 ,  Wei-Chih Chen1 ,  Yang Wang1 ,  Jingjie Li1 ,  Huinan Yin1 ,  Hang Zhang1 ,  Weikang Xu2,5,6* ,  Qingde Wa3*
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1 Department of Orthopaedic Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Haizhu District, Guangzhou, Guangdong, China
2 Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Jianghai Avenue Central, Haizhu District, Guangzhou, Guangdong, China
3 Department of Orthopaedic Surgery, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
4 Department of Orthopaedic Surgery, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingcheng District, Qingyuan, Guangdong, China
5 National Engineering Research Center for Healthcare Devices, Guangdong Provincial Key Laboratory of Medical Electronic Instruments and Materials, Guangdong Institute of Medical Instruments, Tianhe District, Guangzhou, Guangdong, China
6 Guangdong Chinese Medicine Intelligent Diagnosis and Treatment Engineering Technology Research center, Jianghai Avenue Central, Haizhu District, Guangzhou, Guangdong, China
IJB 2024, 10(5), 3551 https://doi.org/10.36922/ijb.3551
Submitted: 30 April 2024 | Accepted: 19 June 2024 | Published: 31 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Bioceramic composite polycaprolactone (PCL) scaffolds are widely used in bone defect repair studies. Among them, bioactive glass (BG) is considered an excellent bone-based repair material due to its unique inorganic amorphous structure, bioactivity, and osseointegration properties. However, the dense pores and low specific surface area of ordinary BGs and mesoporous BGs limit the mechanical properties and bioactivity of the overall scaffolds, and it is often necessary to increase the proportion of BGs to offset these shortcomings. Here, we prepared highly active dendritic mesoporous structured bioactive glass (MBG) with a high specific surface area (457.14 m2/g) and pore volume (1.38 cm3/g) by sol-gel method. PCL scaffolds containing different percentages of MBG were prepared by three-dimensional printing technology, and the physicochemical and immunomodulatory osteogenic properties were investigated. The results showed that the low-concentration MBG/ PCL scaffolds with 10% content (10MBG/PCL) possessed the highest compressive strength (about two times that of pure PCL scaffolds) and excellent in vitro immunomodulatory osteogenic properties. Finally, 10MBG/PCL was selected for further exploration to investigate the effects of different fiber diameters (F300, F500, F800) and pore sizes (P200, P500, P800) on the scaffolds performance. Ultimately, we found that the 10MBG/PCL scaffolds with fiber diameter and pore size of 500 μm had high osteogenic potential, significantly induced macrophage polarization toward the M2 phenotype, and downregulated the expression of inflammatory genes and that this group was the most capable of mediating macrophage polarization and thus inducing the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) to form an immune microenvironment conducive to osteogenesis. This study is a step forward in the exploration of the performance of BG composite PCL scaffolds and provides a new idea for the development of bone graft materials. 

Keywords
3D printing
Dendritic mesoporous structured bioactive glass
Macrophages
Bone marrow mesenchymal stem cells
Immunoregulation
Osteogenic differentiation
Funding
This research was supported by the National Natural Science Foundation of China (32000964, 82160577), the Guangdong Province Science and Technology Plan Project (2024A1515012265, 2020B1111560001, and 2022A1515140193), the Program for Science and Technology Project of Guizhou Province, Qiankehe Platform Talents (No. [2021] 5613), the Key Program for Science and Technology Project of Guizhou Province (No. ZK [2021] 007), and the GDAS’ Project of Science and Technology Development (2022GDASZH-2022020402-01, 2 0 2 2 G D A S Z H - 2 0 2 2 0 1 0 1 1 0 , a n d 2020GDASZH-2022030604-01).
Conflict of interest
The authors declare no conflict of interest.
References
  1. Ye S, Seo K-B, Park B-H, et al. Comparison of the osteogenic potential of bone dust and iliac bone chip. Spine J. 2013;13(11):1659-1666. doi: 10.1016/j.spinee.2013.06.012
  2. Zhang J, Jiang Y, Shang, et al. Biodegradable metals for bone defect repair: A systematic review and meta-analysis based on animal studies. Bioact Mater. 2021;6(11): 4027-4052. doi: 10.1016/j.bioactmat.2021.03.035
  3. Khodakaram-Tafti A, Mehrabani D, Shaterzadeh-Yazdi H, Zamiri B, Omidi, M. Tissue engineering in maxillary bone defects. World J Plast Surg. 2018;7(1):3-11.
  4. Turnbull G, Clarke J, Picard F, et al. 3D bioactive composite scaffolds for bone tissue engineering. Bioact Mater. 2018;3(3):278-314. doi: 10.1016/j.bioactmat.2017.10.001
  5. Siddiqui N, Asawa S, Birru B, Baadhe R, Rao S. PCL-based composite scaffold matrices for tissue engineering applications. Mol Biotechnol. 2018;60(7):506-532. doi: 10.1007/s12033-018-0084-5
  6. Gharibshahian M, Salehi M, Beheshtizadeh N, et al. Recent advances on 3D-printed PCL-based composite scaffolds for bone tissue engineering. Front Bioeng Biotechnol. 2023;11:1168504. doi: 10.3389/fbioe.2023.1168504
  7. Jones JR. Reprint of: review of bioactive glass: from Hench to hybrids. Acta Biomater. 2015;23(Suppl 1):S53-S82. doi: 10.1016/j.actbio.2015.07.019
  8. Hench LL, Polak JM. Third-generation biomedical materials. Science. 2002;295(5557):1014. doi: 10.1126/science.1067404
  9. Kokubo T, Kim HM, Kawashita M. Novel bioactive materials with different mechanical properties. Biomaterials. 2003;24(13):2161-2175. doi: 10.1016/s0142-9612(03)00044-9
  10. Skallevold HE, Rokaya D, Khurshid Z, Zafar MS. Bioactive glass applications in dentistry. Int J Mol Sci. 2019;20(23). doi: 10.3390/ijms20235960
  11. Schumacher M, Habibovic P, van Rijt S. Mesoporous bioactive glass composition effects on degradation and bioactivity. Bioact Mater. 2021;6(7):1921-1931. doi: 10.1016/j.bioactmat.2020.12.007
  12. Zheng K, Boccaccini AR. Sol-gel processing of bioactive glass nanoparticles: a review. Adv Colloid Interface Sci. 2017;249:363-373. doi: 10.1016/j.cis.2017.03.008
  13. El-Fiqi A, Mandakhbayar N, Jo SB, et al. Nanotherapeutics for regeneration of degenerated tissue infected by bacteria through the multiple delivery of bioactive ions and growth factor with antibacterial/angiogenic and osteogenic/ odontogenic capacity. Bioact Mater. 2021;6(1):123-136. doi: 10.1016/j.bioactmat.2020.07.010
  14. Xin T, Gu Y, Cheng R, et al. Inorganic strengthened hydrogel membrane as regenerative periosteum. Acs Appl Mater Interfaces. 2017;9(47):41168-41180. doi: 10.1021/acsami.7b13167
  15. Zhao H, Wang X, Jin A, et al. Reducing relapse and accelerating osteogenesis in rapid maxillary expansion using an injectable mesoporous bioactive glass/fibrin glue composite hydrogel. Bioact Mater. 2022;18:507-525. doi: 10.1016/j.bioactmat.2022.03.001
  16. Wang C, Meng C, Zhang Z, Zhu Q. 3D printing of polycaprolactone/bioactive glass composite scaffolds for in situ bone repair. Ceram Int. 2022;48(6):7491-7499. doi: 10.1016/j.ceramint.2021.11.293
  17. Huang W, Cai X, Xiao C, Song W, Yin H, Xu W. Surface micropatterning of 3D printed PCL scaffolds promotes osteogenic differentiation of BMSCs and regulates macrophage M2 polarization. Heliyon 2024;10(5):e26621-e26621. doi: 10.1016/j.heliyon.2024.e26621
  18. Arron JR, Choi Y. Osteoimmunology - bone versus immune system. Nature. 2000;408(6812):535-536. doi: 10.1038/35046196
  19. Yang N, Liu Y. The role of the immune microenvironment in bone regeneration. Int J Med Sci. 2021;18(16):3697-3707. doi: 10.7150/ijms.61080
  20. Wu Z, Bai J, Ge G, et al. Regulating macrophage polarization in high glucose microenvironment using lithium-modified bioglass-hydrogel for diabetic bone regeneration. Adv Healthc Mater. 2022;11(13). doi: 10.1002/adhm.202200298
  21. Feito MJ, Casarrubios L, Onaderra M, et al. Response of RAW 264.7 and J774A.1 macrophages to particles and nanoparticles of a mesoporous bioactive glass: a comparative study. Colloids Surf B. 2021;208. doi: 10.1016/j.colsurfb.2021.112110
  22. Xu H, Zhu Y, Hsiao AW-T, et al. Bioactive glass-elicited stem cell-derived extracellular vesicles regulate M2 macrophage polarization and angiogenesis to improve tendon regeneration and functional recovery. Biomaterials. 2023;294. doi: 10.1016/j.biomaterials.2023.121998
  23. Zheng K, Niu W, Lei B, Boccaccini AR. Immunomodulatory bioactive glasses for tissue regeneration. Acta Biomater. 2021;133:168-186. doi: 10.1016/j.actbio.2021.08.023
  24. Gomez-Cerezo N, Casarrubios L, Morales I, et al. Effects of a mesoporous bioactive glass on osteoblasts, osteoclasts and macrophages. J Colloid Interface Sci. 2018;528: 309-320. doi: 10.1016/j.jcis.2018.05.099
  25. Huang Y, Wu C, Zhang X, Chang J, Dai K. Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration. Acta Biomater. 2018;66:81-92. doi: 10.1016/j.actbio.2017.08.044
  26. Singh RP, Ramarao P. Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles. Toxicol Sci. 2013;136(1):131-143. doi: 10.1093/toxsci/kft179
  27. Wang X, Zachman AL, Chun YW, Shen F-W, Hwang Y-S, Sung H-J. Polymeric stent materials dysregulate macrophage and endothelial cell functions: implications for coronary artery stent. Int J Cardiol. 2014;174(3):688-695. doi: 10.1016/j.ijcard.2014.04.228
  28. Wang Z, Cui Y, Wang J, et al. The effect of thick fibers and large pores of electrospun poly(ε-caprolactone) vascular grafts on macrophage polarization and arterial regeneration. Biomaterials. 2014;35(22):5700-5710. doi: 10.1016/j.biomaterials.2014.03.078
  29. Abebayehu D, Spence A, Boyan BD, Schwartz Z, Ryan JJ, McClure MJ. Galectin-1 promotes an M2 macrophage response to polydioxanone scaffolds. J Biomed Mater Res Part A. 2017;105(9):2562-2571. doi: 10.1002/jbm.a.36113
  30. Zhu G, Zhang R, Xie Q, et al. Shish-kebab structure fiber with nano and micro diameter regulate macrophage polarization for anti-inflammatory and bone differentiation. Mater Today Bio. 2023;23. doi: 10.1016/j.mtbio.2023.100880
  31. Wang Y, Liao T, Shi M, Liu C, Chen X. Facile synthesis and in vitro bioactivity of radial mesoporous bioactive glasses. Mater Lett. 2017;206:205-209. doi: 10.1016/j.matlet.2017.07.021
  32. Chaudhary S, Ghosal D, Tripathi P, Kumar S. Cellular metabolism: a link connecting cellular behaviour with the physiochemical properties of biomaterials for bone tissue engineering. Biomater Sci. 2023;11(7):2277-2291. doi: 10.1039/d2bm01410f
  33. Lewallen EA, Trousdale WH, Thaler R, et al. Surface roughness of titanium orthopedic implants alters thebiological phenotype of human mesenchymal stromal cells. Tissue Eng Part A. 2021;27(23-24):1503-1516. doi: 10.1089/ten.tea.2020.0369
  34. Yuan B, Zhou S-y, Chen X-s. Rapid prototyping technology and its application in bone tissue engineering. J Zhejiang Univ Sci B. 2017;18(4):303-315. doi: 10.1631/jzus.B1600118
  35. van der Heide D, Cidonio G, Stoddart MJ, D’Este M. 3D printing of inorganic-biopolymer composites for bone regeneration. Biofabrication. 2022;14(4). doi: 10.1088/1758-5090/ac8cb2
  36. Garot C, Bettega G, Picart C. Additive manufacturing of material scaffolds for bone regeneration: toward application in the clinics. Adv Funct Mater. 2021;31(5). doi: 10.1002/adfm.202006967
  37. Feng Y, Zhu S, Mei D, et al. Application of 3D printing technology in bone tissue engineering: a review. Curr Drug Delivery. 2021;18(7):847-861. doi: 10.2174/1567201817999201113100322
  38. Ebrahimi S, Sipaut CS. The effect of liquid phase concentration on the setting time and compressive strength of hydroxyapatite/bioglass composite cement. Nanomaterials. 2021;11(10). doi: 10.3390/nano11102576
  39. Rupp F, Liang L, Geis-Gerstorfer J, Scheideler L, Huettig F. Surface characteristics of dental implants: a review. Dent Mater. 2018;34(1):40-57. doi: 10.1016/j.dental.2017.09.007
  40. Wang L, He S, Wu X, et al. Polyetheretherketone/nano-fluorohydroxyapatite composite with antimicrobial activity and osseointegration properties. Biomaterials. 2014;35(25):6758-6775. doi: 10.1016/j.biomaterials.2014.04.085
  41. Muecksch C, Urbassek HM. Accelerated molecular dynamics study of the effects of surface hydrophilicity on protein adsorption. Langmuir. 2016;32(36): 9156-9162. doi: 10.1021/acs.langmuir.6b02229
  42. Wang X, Molino BZ, Pitkanen S, et al. 3D scaffolds of polycaprolactone/copper-doped bioactive glass: architecture engineering with additive manufacturing and cellular assessments in a coculture of bone marrow stem cells and endothelial cells. Acs Biomater Sci Eng. 2019;5(9): 4496-4510. doi: 10.1021/acsbiomaterials.9b00105
  43. Zhou L, Fan L, Zhang F-M, et al. Hybrid gelatin/oxidized chondroitin sulfate hydrogels incorporating bioactive glass nanoparticles with enhanced mechanical properties, mineralization, and osteogenic differentiation. Bioact Mater. 2021;6(3):890-904. doi: 10.1016/j.bioactmat.2020.09.012
  44. Yazdimamaghani M, Razavi M, Vashaee D, Moharamzadeh K, Boccaccini AR, Tayebi L. Porous magnesium-based scaffolds for tissue engineering. Mater Sci Eng C Mater Biol Appl. 2017;71:1253-1266. doi: 10.1016/j.msec.2016.11.027
  45. Marrella A, Lee TY, Lee DH, et al. Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration. Mater Today. 2018;21(4):362-376. doi: 10.1016/j.mattod.2017.10.005
  46. Axpe E, Oyen ML. Applications of alginate-based bioinks in 3D bioprinting. Int J Mol Sci. 2016;17(12). doi: 10.3390/ijms17121976
  47. Fiocco L, Elsayed H, Badocco D, et al. Direct ink writing of silica-bonded calcite scaffolds from preceramic polymers and fillers. Biofabrication. 2017;9(2). doi: 10.1088/1758-5090/aa6c37
  48. Mastrogiacomo M, Scaglione S, Martinetti R, et al. Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics. Biomaterials. 2006;27(17):3230-3237. doi: 10.1016/j.biomaterials.2006.01.031
  49. Hayashi K, Yanagisawa T, Kishida R, Ishikawa K. Effects of scaffold shape on bone regeneration: tiny shape differences affect the entire system. Acs Nano. 2022;16(8):11755-11768. doi: 10.1021/acsnano.2c03776
  50. Gorustovich AA, Roether JA, Boccaccini AR. Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng Part B Rev. 2010;16(2):199-207. doi: 10.1089/ten.teb.2009.0416
  51. Hench LL. Genetic design of bioactive glass. J Eur Ceram Soc. 2009;29(7):1257-1265. doi: 10.1016/j.jeurceramsoc.2008.08.002
  52. Ajita J, Saravanan S, Selvamurugan N. Effect of size of bioactive glass nanoparticles on mesenchymal stem cell proliferation for dental and orthopedic applications. Mater Sci Eng C Mater Biol Appl. 2015;53:142-149. doi: 10.1016/j.msec.2015.04.041
  53. El-Rashidy AA, Roether JA, Harhaus L, Kneser U, Boccaccini AR. Regenerating bone with bioactive glass scaffolds: a review of in vivo studies in bone defect models. Acta Biomater. 2017;62:1-28. doi: 10.1016/j.actbio.2017.08.030
  54. Sepulveda P, Jones JR, Hench LL. Characterization of melt-derived 45S5 and sol-gel-derived 58S bioactive glasses. J Biomed Mater Res. 2001;58(6):734-740. doi: 10.1002/jbm.10026
  55. Xie W, Fu X, Tang F, et al. Dose-dependent modulation effects of bioactive glass particles on macrophages and diabetic wound healing. J Mater Chem B. 2019;7(6):940-952. doi: 10.1039/c8tb02938e
  56. Gao Q, Xie C, Wang P, et al. 3D printed multi-scale scaffolds with ultrafine fibers for providing excellent biocompatibility. Mater Sci Eng C Mater Biol Appl. 2020;107. doi: 10.1016/j.msec.2019.110269
  57. Sanz M, Dahlin C, Apatzidou D, et al. Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: consensus report of group 2 of the 15th European Workshop on Periodontology on Bone Regeneration. J Clin Periodontol. 2019;46:82-91. doi: 10.1111/jcpe.13123
  58. Yedekci B, Tezcaner A, Yilmaz B, Demir T, Evis Z. 3D porous PCL-PEG-PCL/strontium, magnesium and boron multi-doped hydroxyapatite composite scaffolds for bone tissue engineering. J Mech Behav Biomed Mater. 2022;125. doi: 10.1016/j.jmbbm.2021.104941
  59. Swanson WB, Omi M, Zhang Z, et al. Macropore design of tissue engineering scaffolds regulates mesenchymal stem cell differentiation fate. Biomaterials. 2021;272. doi: 10.1016/j.biomaterials.2021.120769
  60. Wang C, Wu J, Liu L, et al. Improving osteoinduction and osteogenesis of Ti6Al4V alloy porous scaffold by regulating the pore structure. Front Chem. 2023;11. doi: 10.3389/fchem.2023.1190630
  61. Garg K, Pullen NA, Oskeritzian CA, Ryan JJ, Bowlin GL. Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials. 2013;34(18):4439-4451. doi: 10.1016/j.biomaterials.2013.02.065
  62. Horii T, Tsujimoto H, Hagiwara A, et al. Effects of fiber diameter and spacing size of an artificial scaffold on the in vivo cellular response and tissue remodeling. ACS Appl Biomater. 2021;4(9):6924-6936. doi: 10.1021/acsabm.1c00572
  63. Li W, Dai F, Zhang S, et al. Pore size of 3D-printed polycaprolactone/polyethylene glycol/hydroxyapatite scaffolds affects bone regeneration by modulating macrophage polarization and the foreign body response. Acs Appl Mater Interfaces. 2022;14(18):20693-20707. doi: 10.1021/acsami.2c02001
  64. Yang X, Gao J, Yang S, et al. Pore size-mediated macrophage M1 to M2 transition affects osseointegration of 3D-printed PEEK scaffolds. Int J Bioprint. 2023;9(5):128-144. doi: 10.18063/ijb.755

 

 

 



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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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