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Cited by 65Bone Tissue Engineering MaterialsWound Healing and TreatmentsTissue Engineering and Regenerative Medicine

Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold

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Xue, Hang, Zhang, Zhenhe, Lin, Ze, Su, Jin, Panayi, Adriana C., Xiong, Yuan, Hu, Liangcong, Hu, Yiqiang +7 more·2022·Bioactive Materials
DOI 10.1016/j.bioactmat.2022.05.023PMC PMC9256949
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Abstract

Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA; QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.

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  • PLA/hydroxyapatite composite scaffolds with nanohybrid surface modification accelerated bone healing in rats with large bone defects.

    “When applied in vivo to repair large bone defects (animal model, rats), accelerated bone healing was observed.”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [228]

  • Scaffold modification with nanohybrid components positively influenced M2 macrophage polarization, osteogenesis, and angiogenesis.

    “Moreover, scaffold modification with nanohybrid components positively influenced the M2 type of macrophage polarization as well as osteogenesis and angiogenesis.”

    From Resorbable Biomaterials Used for 3D Scaffolds in Tissue Engineering: A Review (2023) · cites this paper as [228]

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  1. [1]Einhorn T.A. Gerstenfeld L.C. Fracture healing: mechanisms and interventions Nat. Rev. Rheumatol. 11 1 2015 45 54 10.1038/nrrheum.2014.164 25266456 PMC4464690 · DOI
  2. [2]Kundu B. Rajkhowa R. Kundu S.C. Wang X. Silk fibroin biomaterials for tissue regenerations Adv. Drug Deliv. Rev. 65 4 2013 457 470 10.1016/j.addr.2012.09.043 23137786 · DOI · Paper page
  3. [3]Eming S.A. Martin P. Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation Sci. Transl. Med. 6 265 2014 265sr6 10.1126/scitranslmed.3009337 25473038 PMC4973620 · DOI · Paper page
  4. [4]Bai L. Chen P. Zhao Y. Hang R. Yao X. Tang B. Liu C. Xiao Y. Hang R. A micro/nano-biomimetic coating on titanium orchestrates osteo/angio-genesis and osteoimmunomodulation for advanced osseointegration Biomaterials 278 2021 121162 10.1016/j.biomaterials.2021.121162 34628191 · DOI
  5. [6]Qiu P. Li M. Chen K. Fang B. Chen P. Tang Z. Lin X. Fan S. Periosteal matrix-derived hydrogel promotes bone repair through an early immune regulation coupled with enhanced angio- and osteogenesis Biomaterials 227 2020 119552 10.1016/j.biomaterials.2019.119552 31670079 · DOI
  6. [7]Marconi G.D. Diomede F. Pizzicannella J. Fonticoli L. Merciaro I. Pierdomenico S.D. Mazzon E. Piattelli A. Trubiani O. Enhanced VEGF/VEGF-R and RUNX2 expression in human periodontal ligament stem cells cultured on sandblasted/etched titanium disk Front. Cell Dev. Biol. 8 2020 315 10.3389/fcell.2020.00315 32478069 PMC7240029 · DOI
  7. [8]Zuo W.H. Zeng P. Chen X. Lu Y.J. Li A. Wu J.B. Promotive effects of bone morphogenetic protein 2 on angiogenesis in hepatocarcinoma via multiple signal pathways Sci. Rep. 6 2016 37499 10.1038/srep37499 27886213 PMC5122863 · DOI
  8. [9]Diomede F. Marconi G.D. Fonticoli L. Pizzicanella J. Merciaro I. Bramanti P. Mazzon E. Trubiani O. Functional relationship between osteogenesis and angiogenesis in tissue regeneration Int. J. Mol. Sci. 21 9 2020 10.3390/ijms21093242 PMC7247346 32375269 · DOI
  9. [10]Ramasamy S.K. Kusumbe A.P. Wang L. Adams R.H. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone Nature 507 7492 2014 376 380 10.1038/nature13146 24647000 PMC4943529 · DOI · Paper page
  10. [11]Xue H. Hu L. Xiong Y. Zhu X. Wei C. Cao F. Zhou W. Sun Y. Endo Y. Liu M. Liu Y. Liu J. Abududilibaier A. Chen L. Yan C. Mi B. Liu G. Quaternized chitosan-Matrigel-polyacrylamide hydrogels as wound dressing for wound repair and regeneration Carbohydr. Polym. 226 2019 115302 10.1016/j.carbpol.2019.115302 31582049 · DOI
  11. [12]Gresham R.C.H. Bahney C.S. Leach J.K. Growth factor delivery using extracellular matrix-mimicking substrates for musculoskeletal tissue engineering and repair Bioact. Mater. 6 7 2021 1945 1956 10.1016/j.bioactmat.2020.12.012 33426369 PMC7773685 · DOI
  12. [13]Xavier J.R. Thakur T. Desai P. Jaiswal M.K. Sears N. Cosgriff-Hernandez E. Kaunas R. Gaharwar A.K. Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach ACS Nano 9 3 2015 3109 3118 10.1021/nn507488s 25674809 · DOI
  13. [14]Lee K.S. Lee J. Kim H.K. Yeom S.H. Woo C.H. Jung Y.J. Yun Y.E. Park S.Y. Han J. Kim E. Sul J.H. Jung J.M. Park J.H. Choi J.S. Cho Y.W. Jo D.G. Extracellular vesicles from adipose tissue-derived stem cells alleviate osteoporosis through osteoprotegerin and miR-21-5p J. Extracell. Vesicles 10 12 2021 e12152 10.1002/jev2.12152 PMC8485335 34596354 · DOI
  14. [15]Peng Z.X. Wang L. Du L. Guo S.R. Wang X.Q. Tang T.T. Adjustment of the antibacterial activity and biocompatibility of hydroxypropyltrimethyl ammonium chloride chitosan by varying the degree of substitution of quaternary ammonium Carbohydr. Polym. 81 2 2010 275 283 10.1016/j.carbpol.2010.02.008 · DOI
  15. [16]Li M. Liang Y.P. He J.H. Zhang H.L. Guo B.L. Two-pronged strategy of biomechanically active and biochemically multifunctional hydrogel wound dressing to accelerate wound closure and wound healing Chem. Mater. 32 23 2020 9937 9953 10.1021/acs.chemmater.0c02823 · DOI
  16. [17]Zhou C. Liu S. Li J. Guo K. Yuan Q. Zhong A. Yang J. Wang J. Sun J. Wang Z. Collagen functionalized with graphene oxide enhanced biomimetic mineralization and in situ bone defect repair ACS Appl. Mater. Interfaces 10 50 2018 44080 44091 10.1021/acsami.8b17636 30475576 · DOI
  17. [18]Cheng W. Zeng X. Chen H. Li Z. Zeng W. Mei L. Zhao Y. Versatile polydopamine platforms: synthesis and promising applications for surface modification and advanced nanomedicine ACS Nano 13 8 2019 8537 8565 10.1021/acsnano.9b04436 31369230 · DOI
  18. [19]Awad A. Fina F. Goyanes A. Gaisford S. Basit A.W. Advances in powder bed fusion 3D printing in drug delivery and healthcare Adv. Drug Deliv. Rev. 174 2021 406 424 10.1016/j.addr.2021.04.025 33951489 · DOI
  19. [20]da Silva D. Kaduri M. Poley M. Adir O. Krinsky N. Shainsky-Roitman J. Schroeder A. Biocompatibility, biodegradation and excretion of polylactic acid (PLA) in medical implants and theranostic systems Chem. Eng. J. 340 2018 9 14 10.1016/j.cej.2018.01.010 31384170 PMC6682490 · DOI
  20. [21]Tang P. Han L. Li P. Jia Z. Wang K. Zhang H. Tan H. Guo T. Lu X. Mussel-Inspired electroactive and antioxidative scaffolds with incorporation of polydopamine-reduced graphene oxide for enhancing skin wound healing ACS Appl. Mater. Interfaces 11 8 2019 7703 7714 10.1021/acsami.8b18931 30714361 · DOI
  21. [22]Ferrigno B. Bordett R. Duraisamy N. Moskow J. Arul M.R. Rudraiah S. Nukavarapu S.P. Vella A.T. Kumbar S.G. Bioactive polymeric materials and electrical stimulation strategies for musculoskeletal tissue repair and regeneration Bioact. Mater. 5 3 2020 468 485 10.1016/j.bioactmat.2020.03.010 32280836 PMC7139146 · DOI
  22. [23]Jiao D. Zheng A. Liu Y. Zhang X. Wang X. Wu J. She W. Lv K. Cao L. Jiang X. Bidirectional differentiation of BMSCs induced by a biomimetic procallus based on a gelatin-reduced graphene oxide reinforced hydrogel for rapid bone regeneration Bioact. Mater. 6 7 2021 2011 2028 10.1016/j.bioactmat.2020.12.003 33426373 PMC7782557 · DOI
  23. [24]Yang R. Li G. Zhuang C. Yu P. Ye T. Zhang Y. Shang P. Huang J. Cai M. Wang L. Cui W. Deng L. Gradient bimetallic ion-based hydrogels for tissue microstructure reconstruction of tendon-to-bone insertion Sci. Adv. 7 26 2021 10.1126/sciadv.abg3816 PMC8221628 34162547 · DOI
  24. [25]Aghazadeh Y. Khan S.T. Nkennor B. Nunes S.S. Cell-based therapies for vascular regeneration: past, present and future Pharmacol. Ther. 231 2022 107976 10.1016/j.pharmthera.2021.107976 34480961 · DOI
  25. [26]Wang Y. El-Deen A.G. Li P. Oh B.H. Guo Z. Khin M.M. Vikhe Y.S. Wang J. Hu R.G. Boom R.M. Kline K.A. Becker D.L. Duan H. Chan-Park M.B. High-performance capacitive deionization disinfection of water with graphene oxide-graft-quaternized chitosan nanohybrid electrode coating ACS Nano 9 10 2015 10142 10157 10.1021/acsnano.5b03763 26389519 · DOI
  26. [27]Ripamonti U. Duarte R. Ferretti C. Re-evaluating the induction of bone formation in primates Biomaterials 35 35 2014 9407 9422 10.1016/j.biomaterials.2014.07.053 25155544 · DOI
  27. [28]Wang P. Zhang L. Yao J. Shi Y. Li P. Ding K. An arabinogalactan from flowers of Panax notoginseng inhibits angiogenesis by BMP2/Smad/Id1 signaling Carbohydr. Polym. 121 2015 328 335 10.1016/j.carbpol.2014.11.073 25659706 · DOI
  28. [29]Nakashima K. Zhou X. Kunkel G. Zhang Z. Deng J.M. Behringer R.R. de Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation Cell 108 1 2002 17 29 10.1016/s0092-8674(01)00622-5 11792318 · DOI · Paper page
  29. [30]Carmeliet P. Angiogenesis in life, disease and medicine Nature 438 7070 2005 932 936 10.1038/nature04478 16355210 · DOI
  30. [31]Gangopahyay A. Oran M. Bauer E.M. Wertz J.W. Comhair S.A. Erzurum S.C. Bauer P.M. Bone morphogenetic protein receptor II is a novel mediator of endothelial nitric-oxide synthase activation J. Biol. Chem. 286 38 2011 33134 33140 10.1074/jbc.M111.274100 21808054 PMC3190885 · DOI
  31. [32]Wang X. Abraham S. McKenzie J.A.G. Jeffs N. Swire M. Tripathi V.B. Luhmann U.F.O. Lange C.A.K. Zhai Z. Arthur H.M. Bainbridge J. Moss S.E. Greenwood J. LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling Nature 499 7458 2013 306 311 10.1038/nature12345 23868260 PMC3836402 · DOI
  32. [33]Joner M. Nakazawa G. Finn A.V. Quee S.C. Coleman L. Acampado E. Wilson P.S. Skorija K. Cheng Q. Xu X. Gold H.K. Kolodgie F.D. Virmani R. Endothelial cell recovery between comparator polymer-based drug-eluting stents J. Am. Coll. Cardiol. 52 5 2008 333 342 10.1016/j.jacc.2008.04.030 18652940 · DOI
  33. [34]Kafle A. Luis E. Silwal R. Pan H.M. Shrestha P.L. Bastola A.K. 3D/4D printing of polymers: fused deposition modelling (FDM), selective laser sintering (SLS), and stereolithography (SLA) Polymers 13 18 2021 10.3390/polym13183101 PMC8470301 34578002 · DOI · Paper page
  34. [35]Fina F. Goyanes A. Gaisford S. Basit A.W. Selective laser sintering (SLS) 3D printing of medicines Int. J. Pharm. 529 1–2 2017 285 293 10.1016/j.ijpharm.2017.06.082 28668582 · DOI · Paper page
  35. [36]Gueche Y.A. Sanchez-Ballester N.M. Cailleaux S. Bataille B. Soulairol I. Selective laser sintering (SLS), a new chapter in the production of solid oral forms (SOFs) by 3D printing Pharmaceutics 13 8 2021 10.3390/pharmaceutics13081212 PMC8399326 34452173 · DOI
  36. [37]Chen W. Nichols L. Brinkley F. Bohna K. Tian W. Priddy M.W. Priddy L.B. Alkali treatment facilitates functional nano-hydroxyapatite coating of 3D printed polylactic acid scaffolds Mater Sci Eng C Mater Biol Appl 120 2021 111686 10.1016/j.msec.2020.111686 33545848 · DOI
  37. [38]Zhao X. Han Y. Li J. Cai B. Gao H. Feng W. Li S. Liu J. Li D. BMP-2 immobilized PLGA/hydroxyapatite fibrous scaffold via polydopamine stimulates osteoblast growth Mater Sci Eng C Mater Biol Appl 78 2017 658 666 10.1016/j.msec.2017.03.186 28576035 · DOI
  38. [39]Hu Y.Q. Wu B. Xiong Y. Tao R.Y. Panayi A.C. Chen L. Tian W.Q. Xue H. Shi L. Zhang X.L. Xiong L.M. Mi B.B. Liu G.H. Cryogenic 3D printed hydrogel scaffolds loading exosomes accelerate diabetic wound healing Chem. Eng. J. 426 2021 17 10.1016/j.cej.2021.130634 · DOI
  39. [40]Mittal M. Siddiqui M.R. Tran K. Reddy S.P. Malik A.B. Reactive oxygen species in inflammation and tissue injury Antioxidants Redox Signal. 20 7 2014 1126 1167 10.1089/ars.2012.5149 PMC3929010 23991888 · DOI · Paper page
  40. [41]Li T. Ma H. Ma H. Ma Z. Qiang L. Yang Z. Yang X. Zhou X. Dai K. Wang J. Mussel-Inspired nanostructures potentiate the immunomodulatory properties and angiogenesis of mesenchymal stem cells ACS Appl. Mater. Interfaces 11 19 2019 17134 17146 10.1021/acsami.8b22017 31008578 · DOI
  41. [42]Lu K.Y. Lin P.Y. Chuang E.Y. Shih C.M. Cheng T.M. Lin T.Y. Sung H.W. Mi F.L. H(2)O(2)-Depleting and O(2)-generating selenium nanoparticles for fluorescence imaging and photodynamic treatment of proinflammatory-activated macrophages ACS Appl. Mater. Interfaces 9 6 2017 5158 5172 10.1021/acsami.6b15515 28120612 · DOI
  42. [43]Feng P. Peng S. Shuai C. Gao C. Yang W. Bin S. Min A. In situ generation of hydroxyapatite on biopolymer particles for fabrication of bone scaffolds owning bioactivity ACS Appl. Mater. Interfaces 12 41 2020 46743 46755 10.1021/acsami.0c13768 32940994 · DOI
  43. [44]Lee H. Dellatore S.M. Miller W.M. Messersmith P.B. Mussel-inspired surface chemistry for multifunctional coatings Science (New York, N.Y.) 318 5849 2007 426 430 10.1126/science.1147241 PMC2601629 17947576 · DOI · Paper page
  44. [45]Miron R.J. Bosshardt D.D. OsteoMacs: key players around bone biomaterials Biomaterials 82 2016 1 19 10.1016/j.biomaterials.2015.12.017 26735169 · DOI
  45. [46]Li Y. Xiao Y. Liu C. The horizon of materiobiology: a perspective on material-guided cell behaviors and tissue engineering Chem. Rev. 117 5 2017 4376 4421 10.1021/acs.chemrev.6b00654 28221776 · DOI
  46. [47]Majidinia M. Sadeghpour A. Yousefi B. The roles of signaling pathways in bone repair and regeneration J. Cell. Physiol. 233 4 2018 2937 2948 10.1002/jcp.26042 28590066 · DOI
  47. [49]Ruiz S. Zhao H. Chandakkar P. Papoin J. Choi H. Nomura-Kitabayashi A. Patel R. Gillen M. Diao L. Chatterjee P.K. He M. Al-Abed Y. Wang P. Metz C.N. Oh S.P. Blanc L. Campagne F. Marambaud P. Correcting Smad1/5/8, mTOR, and VEGFR2 treats pathology in hereditary hemorrhagic telangiectasia models J. Clin. Invest. 130 2 2020 942 957 10.1172/jci127425 31689244 PMC6994128 · DOI

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Authors
Xue, H., Zhang, Z., Lin, Z., Su, J., Panayi, A. C., Xiong, Y., Hu, L., Hu, Y., Chen, L., Yan, C., Xie, X., Shi, Y., Zhou, W., Mi, B., & Liu, G.
Affiliations
  • Wuhan Union Hospital (CN)
  • Brigham and Women's Hospital (US)
  • State Key Laboratory of Materials Processing and Die & Mould Technology (CN)
Corresponding author
  • Mi, Bobin
  • Liu, Guohui
ORCID
Venue
Bioactive Materials
Publisher
Elsevier BV
Published
2022-12
Volume
18
Pages
552-568
ISSN
  • 2097-1192 (ISSN-L)
  • 2452-199X
DOI
10.1016/j.bioactmat.2022.05.023
PMC
PMC9256949
OpenAlex
W4281816153
Cited by
65
References
2
Citations by year
2026: 7 · 2025: 17 · 2024: 17 · 2023: 21 · 2022: 3
FWCI
4.15
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioactive Materials (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)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
tissue regeneration, angiogenesis, bone formation, quaternized chitosan, graphene oxide, polydopamine, hybrid nanostructures, wound healing, bone regeneration, selective laser sintering, reactive oxygen species, M2 macrophage polarization, BMP2 signaling, Runx2, immunomodulation

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