Skip to main content
SpringerLink
Log in

3D printed β-sheet-reinforced natural polymer hydrogel bilayer tissue engineering scaffold

  • Article
  • Published:
Science China Technological Sciences Aims and scope Submit manuscript

Abstract

It remains a significant challenge to fabricate natural polymer (NP) hydrogels with anti-swelling ability and high strengths in the physiological environment. Herein, the β-sheet-reinforced NP hydrogel is developed by copolymerizing methacrylated gelatin (GelMA) and methacrylated silk fibroin (SFMA) in aqueous solution, followed by ethanol treatment (named GelMA-SFMA-AL). The β-sheets formed by SFMA can act as a stable physical crosslink to enhance the mechanical properties and prolong the degradation of the GelMA network. Importantly, the chemical crosslinking in the GelMA-SFMA hydrogel prevents excessive aggregation of hydrophobic β-sheets, thereby avoiding the formation of brittle hydrogel. The obtained GelMA-SFMA-AL hydrogels exhibit considerably enhanced mechanical properties (Young’s modulus: 0.89–3.68 MPa; tensile strength: 0.31–0.96 MPa; toughness: 0.09–0.63 MJ/m3; compressive modulus: 0.78–2.20 MPa; compressive strength: 2.65–5.93 MPa) compared with GelMA-SFMA hydrogels (Young’s modulus: 0.04–0.13 MPa; tensile strength: 0.04–0.07 MPa; toughness: 0.01–0.02 MJ/m3; compressive modulus: 0.03–0.09 MPa; compressive strength: 0.30–0.64 MPa). A bilayer osteochondral scaffold is constructed via digital light processing (DLP) three-dimensiaonl (3D) printing technology, comprising GelMA-SFMA@diclofenac sodium (DS)-AL as the top layer and GelMA-SFMA@bioactive glass (BG)-AL as the bottom layer. The bilayer hydrogel scaffold is demonstrated to support cell attachment and spreading, and facilitate osteogenic differentiation of rat bone marrow stem cells in vitro. In vivo implantation experiment suggests this bilayer scaffold is promising to be used for osteo-chondral tissue regeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Zhao W, Jin X, Cong Y, et al. Degradable natural polymer hydrogels for articular cartilage tissue engineering. J Chem Technol Biotechnol, 2013, 88: 327–339

    Article  Google Scholar 

  2. Zhang X, Sun Y, Wu T, et al. Combined intramyocardial injectable hydrogel and pericardial adhesive hydrogel patch therapy strategy to achieve gene/ion/gas delivery for improving cardiac function. Nano Today, 2023, 50: 101861

    Article  Google Scholar 

  3. Silberman E, Oved H, Namestnikov M, et al. Post-maturation reinforcement of 3D-printed vascularized cardiac tissues. Adv Mater, 2023, 35: 2302229

    Article  Google Scholar 

  4. Wang L, Li A, Zhang D, et al. Injectable double-network hydrogel for corneal repair. Chem Eng J, 2023, 455: 140698

    Article  Google Scholar 

  5. Cui Z K, Kim S, Baljon J J, et al. Microporous methacrylated glycol chitosan-montmorillonite nanocomposite hydrogel for bone tissue engineering. Nat Commun, 2019, 10: 3523

    Article  Google Scholar 

  6. Zhang G, Lv L, Deng Y, et al. Self-healing gelatin hydrogels cross-linked by combining multiple hydrogen bonding and ionic coordination. Macromol Rapid Commun, 2017, 38: 1700018

    Article  Google Scholar 

  7. Shi M Y, Jiang L J, Yu C J, et al. A robust polyacrylic acid/chitosan cryogel for rapid hemostasis. Sci China Tech Sci, 2022, 65: 1029–1042

    Article  Google Scholar 

  8. Shepherd J H, Ghose S, Kew S J, et al. Effect of fiber crosslinking on collagen-fiber reinforced collagen-chondroitin-6-sulfate materials for regenerating load-bearing soft tissues. J Biomed Mater Res B Appl BioMater, 2013, 101A: 176–184

    Article  Google Scholar 

  9. Liu K Q, Liu Y N, Duan Z G, et al. A biomimetic bi-layered tissue engineering scaffolds for osteochondral defects repair. Sci China Tech Sci, 2021, 64: 793–805

    Article  Google Scholar 

  10. He B, Wang J, Xie M, et al. 3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration. Bioactive Mater, 2022, 17: 234–247

    Article  Google Scholar 

  11. Montazerian H, Baidya A, Haghniaz R, et al. Stretchable and bioadhesive gelatin methacryloyl-based hydrogels enabled by in situ dopamine polymerization. ACS Appl Mater Interfaces, 2021, 13: 40290–40301

    Article  Google Scholar 

  12. Kim S H, Yeon Y K, Lee J M, et al. Precisely printable and biocompatible silk fibroin bioink for digital light processing 3D printing. Nat Commun, 2018, 9: 1620

    Article  Google Scholar 

  13. Bian X, Cui C, Qi Y, et al. Amino acid surfactant-induced superfast gelation of silk fibroin for treating noncompressible hemorrhage. Adv Funct Mater, 2022, 32: 2207349

    Article  Google Scholar 

  14. Grant A M, Kim H S, Dupnock T L, et al. Silk fibroin-substrate interactions at heterogeneous nanocomposite interfaces. Adv Funct Mater, 2016, 26: 6380–6392

    Article  Google Scholar 

  15. Kaewprasit K, Kobayashi T, Damrongsakkul S. Alcohol-triggered silk fibroin hydrogels having random coil and β-turn structures enhanced for cytocompatible cell response. J Appl Polym Sci, 2020, 137: 48731

    Article  Google Scholar 

  16. Quan H, Zhang T, Xu H, et al. Photo-curing 3D printing technique and its challenges. Bioactive Mater, 2020, 5: 110–115

    Article  Google Scholar 

  17. Hong H, Seo Y B, Kim D Y, et al. Digital light processing 3D printed silk fibroin hydrogel for cartilage tissue engineering. Biomaterials, 2020, 232: 119679

    Article  Google Scholar 

  18. Wu T, Cui C, Fan C, et al. Tea eggs-inspired high-strength natural polymer hydrogels. Bioactive Mater, 2021, 6: 2820–2828

    Article  Google Scholar 

  19. Kilic Bektas C, Hasirci V. Mimicking corneal stroma using keratocyte-loaded photopolymerizable methacrylated gelatin hydrogels. J Tissue Eng Regen Med, 2018, 12: e1899–e1910

    Article  Google Scholar 

  20. Rajput M, Mondal P, Yadav P, et al. Light-based 3D bioprinting of bone tissue scaffolds with tunable mechanical properties and architecture from photocurable silk fibroin. Int J Biol Macromol, 2022, 202: 644–656

    Article  Google Scholar 

  21. Huang W, Ebrahimi D, Dinjaski N, et al. Synergistic integration of experimental and simulation approaches for the de novo design of silk-based materials. Acc Chem Res, 2017, 50: 866–876

    Article  Google Scholar 

  22. Dai X, Zhang Y, Gao L, et al. A mechanically strong, highly stable, thermoplastic, and self-healable supramolecular polymer hydrogel. Adv Mater, 2015, 27: 3566–3571

    Article  Google Scholar 

  23. Tan L S, Tan H L, Deekonda K, et al. Fabrication of radiation cross-linked diclofenac sodium loaded carboxymethyl sago pulp/chitosan hydrogel for enteric and sustained drug delivery. Carbohyd Polym Technol Appl, 2021, 2: 100084

    Google Scholar 

  24. Zhao M, Qi Z, Tao X, et al. Chemical, thermal, time, and enzymatic stability of silk materials with silk i structure. Int J Mol Sci, 2021, 22: 4136

    Article  Google Scholar 

  25. Gil E S, Park S H, Hu X, et al. impact ofsterilization on the enzymatic degradation and mechanical properties of silk biomaterials. Macromol Biosci, 2014, 14: 257–269

    Article  Google Scholar 

  26. Zhu Z, Ling S, Yeo J, et al. High-strength, durable all-silk fibroin hydrogels with versatile processability toward multifunctional applications. Adv Funct Mater, 2018, 28: 1704757

    Article  Google Scholar 

  27. Nogueira G M, Rodas A C D, Leite C A P, et al. Preparation and characterization of ethanol-treated silk fibroin dense membranes for biomaterials application using waste silk fibers as raw material. Bioresource Tech, 2010, 101: 8446–8451

    Article  Google Scholar 

  28. Chen X, Shao Z, Knight D P, et al. Conformation transition kinetics of Bombyx mori silk protein. Proteins, 2007, 68: 223–231

    Article  Google Scholar 

  29. Lin Y, Xia X, Shang K, et al. Tuning chemical and physical crosslinks in silk electrogels for morphological analysis and mechanical reinforcement. Biomacromolecules, 2013, 14: 2629–2635

    Article  Google Scholar 

  30. Li T, Song X, Weng C, et al. Silk fibroin/carboxymethyl chitosan hydrogel with tunable biomechanical properties has application potential as cartilage scaffold. Int J Biol Macromol, 2019, 137: 382–391

    Article  Google Scholar 

  31. Fan L, Wang H, Zhang K, et al. Regenerated silk fibroin nanofibrous matrices treated with 75% ethanol vapor for tissue-engineering applications. J Biomater Sci Polym Ed, 2012, 23: 497–508

    Article  Google Scholar 

  32. Heinemann P, Kasperski M. Damping induced by walking and running. Procedia Eng, 2017, 199: 2826–2831

    Article  Google Scholar 

  33. Gao F, Xu Z, Liang Q, et al. Osteochondral regeneration with 3D-printed biodegradable high-strength supramolecular polymer re-inforced-gelatin hydrogel scaffolds. Adv Sci, 2019, 6: 1900867

    Article  Google Scholar 

  34. Maver U, Xhanari K, Zizek M, et al. Carboxymethyl cellulose/diclofenac bioactive coatings on AISI 316LVM for controlled drug delivery, and improved osteogenic potential. Carbohyd Polym, 2020, 230: 115612

    Article  Google Scholar 

  35. Altman R, Bosch B, Brune K, et al. Advances in NSAID development: Evolution of diclofenac products using pharmaceutical technology. Drugs, 2015, 75: 859–877

    Article  Google Scholar 

  36. Xin B, Li Z J, Wang Y S, et al. Effect of diclofenac sodium on chondrocyte inflammation and synovial macrophage polarization in osteoarthritis rat model (in Chinese). J Clinical Exp Med, 2022, 21: 1671–4695

    Google Scholar 

  37. Zhou Z J, Zhang L Y, Li F G, et al. Effects of compound diclofenac sodium on cartilage morphology and oxidative stress in osteoarthritis rats (in Chinese). Chin J Tissue Eng Res, 2023, 27: 4154–4160

    Google Scholar 

  38. El-Rashidy A A, Roether J A, Harhaus L, et al. Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models. Acta Biomater, 2017, 62: 1–28

    Article  Google Scholar 

  39. Sun Y, Gao Z, Zhang X, et al. 3D-printed, bi-layer, biomimetic artificial periosteum for boosting bone regeneration. Bio-Des Manuf, 2022, 5: 540–555

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, China

    XinRui Zhao, XiongFeng Nie, XiaoPing Zhang, YaGe Sun, Rong Yang, XinYu Bian, Qian Zhang, HongYing Wang, ZiYang Xu & WenGuang Liu

Authors
  1. XinRui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. XiongFeng Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. XiaoPing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. YaGe Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. XinYu Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. HongYing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. ZiYang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. WenGuang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to ZiYang Xu or WenGuang Liu.

Additional information

This work was supported by the National Key Research and Development Program of China (Grant No. 2018YFA0703100).

Supporting Information

The supporting information is available online at https://tech.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Supporting Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, X., Nie, X., Zhang, X. et al. 3D printed β-sheet-reinforced natural polymer hydrogel bilayer tissue engineering scaffold. Sci. China Technol. Sci. 67, 1170–1184 (2024). https://doi.org/10.1007/s11431-023-2471-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11431-023-2471-0

Search

Navigation