Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration

Zijun MA; Wendan JIA; Xiaoyuan WANG; Rong CHENG; Lu HAN; Meng LI; Xiaoning YANG; Shengbo SANG

doi:10.1631/jzus.B2500343

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Research Article | Updated：2025-12-31

Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration
Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration
一种具有生物相容性和机械强度的新型多组分协同生物墨水用于促进软骨再生
Journal of Zhejiang University-SCIENCE B Vol. 26, Issue 12, Pages: 1156-1171(2025)
Affiliations：

1.Shanxi Key Laboratory of Artificial Intelligence & Micro Nano Sensors, College of Integrated Circuits, Taiyuan University of Technology, Taiyuan 030024, China
2.Key Lab of Advanced Transducers and Intelligent Control System of the Ministry of Education, Taiyuan University of Technology, Taiyuan 030024, China
3.Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030024, China
Funds：
DOI：10.1631/jzus.B2500343
CLC：
CSTR：
Received：17 June 2025，

Revised：2025-10-04，

Published：15 December 2025
Accepted：

马梓钧,贾雯丹,王晓圆等.一种具有生物相容性和机械强度的新型多组分协同生物墨水用于促进软骨再生[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(12):1156-1171.

Zijun MA, Wendan JIA, Xiaoyuan WANG, et al. Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration[J]. Journal of Zhejiang University-SCIENCE B, 2025, 26(12): 1156-1171.
马梓钧,贾雯丹,王晓圆等.一种具有生物相容性和机械强度的新型多组分协同生物墨水用于促进软骨再生[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(12):1156-1171. DOI： 10.1631/jzus.B2500343.

Zijun MA, Wendan JIA, Xiaoyuan WANG, et al. Novel multi-component synergistic bioink that balances biocompatibility and mechanical strength for cartilage regeneration[J]. Journal of Zhejiang University-SCIENCE B, 2025, 26(12): 1156-1171. DOI： 10.1631/jzus.B2500343.

摘要

水凝胶因其类似于细胞外基质的多孔网络结构，已成为软骨组织工程领域必不可少的支架材料。其中，甲基丙烯酸明胶（GelMA）水凝胶因其优异的生物相容性、生物降解性和可调的光交联性能而广泛应用于生物墨水开发。然而，纯GelMA的高生物相容性往往以机械强度为代价，限制了其在软骨再生中的适用性。为了克服这种制约关系，本研究开发了基于GelMA、丝素蛋白（SF）和聚环氧乙烷（PEO）的复合生物墨水，用于制备多孔水凝胶支架，然后从形貌、孔隙率、亲水性、机械强度、流变行为、可印刷性和细胞相容性等方面对其进行了系统表征。在这种设计中，PEO作为致孔剂产生高度多孔的结构（孔隙率高达88%），而SF补偿了PEO造成的机械损失，使支架能够保持高达29.10 kPa的压缩强度。在测试的配方中，10% GelMA/1% SF/1.5% PEO（1%=0.01 g/mL）生物墨水表现出优异的打印性能、机械性能和细胞相容性，并且在打印后支持软骨细胞对II型胶原和聚集蛋白聚糖的牢固沉积。这项工作为平衡生物墨水的生物相容性和机械性能提供了一种多功能策略，为下一代软骨组织工程支架提供了一个有前景的平台。

Abstract

Hydrogels

owing to their porous network structure resembling the extracellular matrix (ECM)

have become essential scaffold materials in the field of cartilage tissue engineering. Among them

gelatin methacrylate (GelMA) hydrogels are widely used in bioink development due to their excellent biocompatibility

biodegradability

and tunable photo-crosslinking properties. However

the high biocompatibility of pure GelMA often comes at the cost of mechanical strength

limiting its applicability in cartilage regeneration. To overcome this trade-off

this study developed composite bioinks based on GelMA

silk fibroin (SF)

and polyethylene oxide (PEO) for fabricating porous hydrogel scaffolds

which were then systematically characterized in terms of morphology

porosity

hydrophilicity

mechanical strength

rheological behavior

printability

and cytocompatibility. In this design

PEO serves as a porogen to generate highly porous structures (porosity up to 88%)

while SF compensates for the mechanical loss caused by PEO

enabling the scaffold to retain a compression strength of up to 29.10 kPa. Among the tested formulations

the 10% GelMA/1% SF/1.5% PEO (1%=0.01 g/mL) bioink exhibited excellent printability

mechanical integrity

and cytocompatibility

and it supported a robust deposition of collagen II and aggrecan by chondrocytes after printing. This work provides a versatile strategy for balancing the biocompatibility and mechanical robustness in bioinks

offering a promising platform for next-generation cartilage tissue engineering scaffolds.

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references

Appel EA , Tibbitt MW , Webber MJ , et al. , 2015 . Self-assembled hydrogels utilizing polymer‒nanoparticle interactions . Nat Commun , 6 : 6295 . https://doi.org/10.1038/ncomms7295 https://doi.org/10.1038/ncomms7295

Arguchinskaya NV , Isaeva EV , Kisel AA , et al. , 2023 . Properties and printability of the synthesized hydrogel based on GeLMA . Int J Mol Sci , 24 ( 3 ): 2121 . https://doi.org/10.3390/ijms24032121 https://doi.org/10.3390/ijms24032121

Bai L , Jing YY , Reis RL , et al. , 2025 . Organoid research: theory, technology, and therapeutics . Organoid Res , 1 ( 1 ): 025040007 . https://doi.org/10.36922/or025040007 https://doi.org/10.36922/or025040007

Brunel LG , Hull SM , Heilshorn SC , 2022 . Engineered assistive materials for 3D bioprinting: support baths and sacrificial inks . Biofabrication , 14 ( 3 ): 032001 . https://doi.org/10.1088/1758-5090/ac6bbe https://doi.org/10.1088/1758-5090/ac6bbe

Cao YY , Cheng P , Sang SB , et al. , 2021 . 3D printed PCL/GelMA biphasic scaffold boosts cartilage regeneration using co-culture of mesenchymal stem cells and chondrocytes: in vivo study . Mater Des , 210 : 110065 . https://doi.org/10.1016/j.matdes.2021.110065 https://doi.org/10.1016/j.matdes.2021.110065

Chen SS , Wang Y , Lai JH , et al. , 2023 . Structure and properties of gelatin methacryloyl (GelMA) synthesized in different reaction systems . Biomacromolecules , 24 ( 6 ): 2928 - 2941 . https://doi.org/10.1021/acs.biomac.3c00302 https://doi.org/10.1021/acs.biomac.3c00302

de Girolamo L , Ragni E , Cucchiarini M , et al. , 2019 . Cells, soluble factors and matrix harmonically play the concert of allograft integration . Knee Surg Sports Traumatol Arthrosc , 27 ( 6 ): 1717 - 1725 . https://doi.org/10.1007/s00167-018-5182-1 https://doi.org/10.1007/s00167-018-5182-1

Findeisen S , Gräfe N , Schwilk M , et al. , 2023 . Use of autologous bone graft with bioactive glass as a bone substitute in the treatment of large-sized bone defects of the femur and tibia . J Pers Med , 13 ( 12 ): 1644 . https://doi.org/10.3390/jpm13121644 https://doi.org/10.3390/jpm13121644

He P , Zhao YB , Wang B , et al. , 2024 . A biodegradable magnesium phosphate cement incorporating chitosan and rhBMP-2 designed for bone defect repair . J Orthop Transl , 49 : 167 - 180 . https://doi.org/10.1016/j.jot.2024.08.004 https://doi.org/10.1016/j.jot.2024.08.004

Hou MZ , Zhang YJ , Liu Y , et al. , 2023 . Biomimetic melatonin-loaded silk fibroin/GelMA scaffold strengthens cartilage repair through retrieval of mitochondrial functions . J Mater Sci Technol , 146 : 102 - 112 . https://doi.org/10.1016/j.jmst.2022.10.031 https://doi.org/10.1016/j.jmst.2022.10.031

Huang DY , Li YH , Ma ZH , et al. , 2023 . Collagen hydrogel viscoelasticity regulates MSC chondrogenesis in a ROCK-dependent manner . Sci Adv , 9 ( 6 ): eade9497 . https://doi.org/10.1126/sciadv.ade9497 https://doi.org/10.1126/sciadv.ade9497

Isreb A , Baj K , Wojsz M , et al. , 2019 . 3D printed oral theophylline doses with innovative ‘radiator-like’ design: impact of polyethylene oxide (PEO) molecular weight . Int J Pharm , 564 : 98 - 105 . https://doi.org/10.1016/j.ijpharm.2019.04.017 https://doi.org/10.1016/j.ijpharm.2019.04.017

Jeong SH , Hiemstra J , Blokzijl PV , et al. , 2024 . An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs . Bio-Des Manuf , 7 ( 3 ): 240 - 261 . https://doi.org/10.1007/s42242-024-00281-7 https://doi.org/10.1007/s42242-024-00281-7

Jia LT , Hua YJ , Zeng JS , et al. , 2022 . Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix . Bioact Mater , 16 : 66 - 81 . https://doi.org/10.1016/j.bioactmat.2022.02.032 https://doi.org/10.1016/j.bioactmat.2022.02.032

Lee SS , Du XY , Kim I , et al. , 2022 . Scaffolds for bone-tissue engineering . Matter , 5 ( 9 ): 2722 - 2759 . https://doi.org/10.1016/j.matt.2022.06.003 https://doi.org/10.1016/j.matt.2022.06.003

Li M , Sun L , Liu ZX , et al. , 2023 . 3D bioprinting of heterogeneous tissue-engineered skin containing human dermal fibroblasts and keratinocytes . Biomater Sci , 11 ( 7 ): 2461 - 2477 . https://doi.org/10.1039/d2bm02092k https://doi.org/10.1039/d2bm02092k

Li M , Liu ZX , Shen ZZ , et al. , 2024 . A heparin-functionalized bioink with sustained delivery of vascular endothelial growth factor for 3D bioprinting of prevascularized dermal constructs . Int J Biol Macromol , 262 : 130075 . https://doi.org/10.1016/j.ijbiomac.2024.130075 https://doi.org/10.1016/j.ijbiomac.2024.130075

Li MX , Song P , Wang WZ , et al. , 2022 . Preparation and characterization of biomimetic gradient multi-layer cell-laden scaffolds for osteochondral integrated repair . J Mater Chem B , 10 ( 22 ): 4172 - 4188 . https://doi.org/10.1039/d2tb00576j https://doi.org/10.1039/d2tb00576j

Liu M , Zeng X , Ma C , et al. , 2017 . Injectable hydrogels for cartilage and bone tissue engineering . Bone Res , 5 : 17014 . https://doi.org/10.1038/boneres.2017.14 https://doi.org/10.1038/boneres.2017.14

Liu Y , Yu L , Zhang D , et al. , 2022 . Manufacture and preliminary evaluation of acellular tooth roots as allografts for alveolar ridge augmentation . J Biomed Mater Res A , 110 : 122 - 130 . https://doi.org/10.1002/jbm.a.37270 https://doi.org/10.1002/jbm.a.37270

Lu XT , Song WJ , Sun XM , et al. , 2022 . Porous hydrogel constructs based on methacrylated gelatin/polyethylene oxide for corneal stromal regeneration . Mater Today Commun , 32 : 104071 . https://doi.org/10.1016/j.mtcomm.2022.104071 https://doi.org/10.1016/j.mtcomm.2022.104071

Ma WP , Lu HX , Xiao Y , et al. , 2025 . Advancing organoid development with 3D bioprinting . Organoid Res , 1 ( 1 ): 025040004 . https://doi.org/10.36922/or025040004 https://doi.org/10.36922/or025040004

Manohar SS , Das C , Kakati V , 2024 . Bone tissue engineering scaffolds: materials and methods . 3D Print Addit Manuf , 11 ( 1 ): 347 - 362 . https://doi.org/10.1089/3dp.2022.0216 https://doi.org/10.1089/3dp.2022.0216

Müller SA , Barg A , Vavken P , et al. , 2016 . Autograft versus sterilized allograft for lateral calcaneal lengthening osteotomies . Medicine , 95 ( 30 ): e4343 . https://doi.org/10.1097/md.0000000000004343 https://doi.org/10.1097/md.0000000000004343

Ng WL , Huang X , Shkolnikov V , et al. , 2023 . Polyvinylpyrrolidone-based bioink: influence of bioink properties on printing performance and cell proliferation during inkjet-based bioprinting . Bio-Des Manuf , 6 ( 6 ): 676 - 690 . https://doi.org/10.1007/s42242-023-00245-3 https://doi.org/10.1007/s42242-023-00245-3

Ning LQ , Mehta R , Cao C , et al. , 2020 . Embedded 3D bioprinting of gelatin methacryloyl-based constructs with highly tunable structural fidelity . ACS Appl Mater Interfaces , 12 ( 40 ): 44563 - 44577 . https://doi.org/10.1021/acsami.0c15078 https://doi.org/10.1021/acsami.0c15078

Pattanashetti NA , Viana T , Alves N , et al. , 2020 . Development of novel 3D scaffolds using BioExtruder by varying the content of hydroxyapatite and silica in PCL matrix for bone tissue engineering . J Polym Res , 27 ( 4 ): 87 . https://doi.org/10.1007/s10965-020-02053-0 https://doi.org/10.1007/s10965-020-02053-0

Sang SB , Mao XJ , Cao YY , et al. , 2023 . 3D bioprinting using synovium-derived MSC-laden photo-cross-linked ECM bioink for cartilage regeneration . ACS Appl Mater Interfaces , 15 ( 7 ): 8895 - 8913 . https://doi.org/10.1021/acsami.2c19058 https://doi.org/10.1021/acsami.2c19058

Seymour AJ , Shin S , Heilshorn SC , 2021 . 3D printing of microgel scaffolds with tunable void fraction to promote cell infiltration . Adv Healthc Mater , 10 ( 18 ): 2100644 . https://doi.org/10.1002/adhm.202100644 https://doi.org/10.1002/adhm.202100644

Sharifi S , Sharifi H , Akbari A , et al. , 2021 . Systematic optimization of visible light-induced crosslinking conditions of gelatin methacryloyl (GelMA) . Sci Rep , 11 : 23276 . https://doi.org/10.1038/s41598-021-02830-x https://doi.org/10.1038/s41598-021-02830-x

Shi XH , Bai Y , He XM , et al. , 2022 . Shaoyao Gancao Decoction for limb dysfunction after fractures around the knee . Medicine , 101 ( 11 ): e29051 . https://doi.org/10.1097/md.0000000000029051 https://doi.org/10.1097/md.0000000000029051

Tuchman A , Brodke DS , Youssef JA , et al. , 2016 . Iliac crest bone graft versus local autograft or allograft for lumbar spinal fusion: a systematic review . Global Spine J , 6 ( 6 ): 592 - 606 . https://doi.org/10.1055/s-0035-1570749 https://doi.org/10.1055/s-0035-1570749

Verma V , Verma P , Kar S , et al. , 2007 . Fabrication of agar-gelatin hybrid scaffolds using a novel entrapment method for in vitro tissue engineering applications . Biotechnol Bioeng , 96 ( 2 ): 392 - 400 . https://doi.org/10.1002/bit.21111 https://doi.org/10.1002/bit.21111

Wang C , Huang W , Zhou Y , et al. , 2020 . 3D printing of bone tissue engineering scaffolds . Bioact Mater , 5 ( 1 ): 82 - 91 . https://doi.org/10.1016/j.bioactmat.2020.01.004 https://doi.org/10.1016/j.bioactmat.2020.01.004

Wang WZ , Zhang BQ , Li MX , et al. , 2021 . 3D printing of PLA/n-HA composite scaffolds with customized mechanical properties and biological functions for bone tissue engineering . Compos Part B Eng , 224 : 109192 . https://doi.org/10.1016/j.compositesb.2021.109192 https://doi.org/10.1016/j.compositesb.2021.109192

Wang YT , Hou Y , Hao T , et al. , 2024 . Model construction and clinical therapeutic potential of engineered cardiac organoids for cardiovascular diseases . Biomater Transl , 5 ( 4 ): 337 - 354 . https://doi.org/10.12336/biomatertransl.2024.04.002 https://doi.org/10.12336/biomatertransl.2024.04.002

Wang Z , Wang X , Huang Y , et al. , 2024 . Ca v 3.3-mediated endochondral ossification in a three-dimensional bioprinted GelMA hydrogel . Bio-Des Manuf , 7 ( 6 ): 983 - 999 . https://doi.org/10.1007/s42242-024-00287-1 https://doi.org/10.1007/s42242-024-00287-1

Xia YL , Wang HY , Li YH , et al. , 2022 . Engineered bone cement trigger bone defect regeneration . Front Mater , 9 : 929618 . https://doi.org/10.3389/fmats.2022.929618 https://doi.org/10.3389/fmats.2022.929618

Xie MJ , Gao Q , Zhao HM , et al. , 2019 . Electro-assisted bioprinting of low-concentration GelMA microdroplets . Small , 15 ( 4 ): 1804216 . https://doi.org/10.1002/smll.201804216 https://doi.org/10.1002/smll.201804216

Xue NN , Ding XF , Huang RZ , et al. , 2022 . Bone tissue engineering in the treatment of bone defects . Pharmaceuticals , 15 ( 7 ): 879 . https://doi.org/10.3390/ph15070879 https://doi.org/10.3390/ph15070879

Xue YM , Kim HJ , Lee J , et al. , 2022 . Co-electrospun silk fibroin and gelatin methacryloyl sheet seeded with mesenchymal stem cells for tendon regeneration . Small , 18 ( 21 ): 2107714 . https://doi.org/10.1002/smll.202107714 https://doi.org/10.1002/smll.202107714

Yang JR , He HM , Li D , et al. , 2023 . Advanced strategies in the application of gelatin-based bioink for extrusion bioprinting . Bio-Des Manuf , 6 ( 5 ): 586 - 608 . https://doi.org/10.1007/s42242-023-00236-4 https://doi.org/10.1007/s42242-023-00236-4

Yi SL , Liu Q , Luo ZY , et al. , 2022 . Micropore-forming gelatin methacryloyl (GelMA) bioink toolbox 2.0: designable tunability and adaptability for 3D bioprinting applications . Small , 18 ( 25 ): 2106357 . https://doi.org/10.1002/smll.202106357 https://doi.org/10.1002/smll.202106357

Ying GL , Jiang N , Maharjan S , et al. , 2018 . Aqueous two-phase emulsion bioink-enabled 3D bioprinting of porous hydrogels . Adv Mater , 30 ( 50 ): 1805460 . https://doi.org/10.1002/adma.201805460 https://doi.org/10.1002/adma.201805460

Yuan X , Zhu W , Yang ZY , et al. , 2024 . Recent advances in 3D printing of smart scaffolds for bone tissue engineering and regeneration . Adv Mater , 36 ( 34 ): 2403641 . https://doi.org/10.1002/adma.202403641 https://doi.org/10.1002/adma.202403641

Zhang LY , Bi Q , Zhao C , et al. , 2020 . Recent advances in biomaterials for the treatment of bone defects . Organogenesis , 16 ( 4 ): 113 - 125 . https://doi.org/10.1080/15476278.2020.1808428 https://doi.org/10.1080/15476278.2020.1808428

Zhang YS , Yu WH , 2025 . Recent advances in bionic scaffolds for cartilage tissue engineering . Front Bioeng Biotechnol , 13 : 1625550 . https://doi.org/10.3389/fbioe.2025.1625550 https://doi.org/10.3389/fbioe.2025.1625550

Zhang YW , Li ZX , Guan JJ , et al. , 2021 . Hydrogel: a potential therapeutic material for bone tissue engineering . AIP Adv , 11 ( 1 ): 010701 . https://doi.org/10.1063/5.0035504 https://doi.org/10.1063/5.0035504

Zheng KW , Zheng X , Yu MZ , et al. , 2023 . BMSCs-seeded interpenetrating network GelMA/SF composite hydrogel for articular cartilage repair . J Funct Biomater , 14 ( 1 ): 39 . https://doi.org/10.3390/jfb14010039 https://doi.org/10.3390/jfb14010039

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Related Author

Jinxing HU

Zhiwei JIANG

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Related Institution

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Disease, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province

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