3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

Ke Yao; Gaoying Hong; Ximin Yuan; Weicheng Kong; Pengcheng Xia; Yuanrong Li; Yuewei Chen; Nian Liu; Jing He; Jue Shi; Zihe Hu; Yanyan Zhou; Zhijian Xie; Yong He

doi:10.1007/s40820-024-01524-z

Nano-Micro Letters, Volume. 17, Issue 1, 027(2025)

3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

Ke Yao^1、†, Gaoying Hong^4、†, Ximin Yuan⁵, Weicheng Kong¹, Pengcheng Xia⁶, Yuanrong Li¹, Yuewei Chen¹, Nian Liu¹, Jing He¹, Jue Shi⁴, Zihe Hu⁴, Yanyan Zhou⁴, Zhijian Xie^4、*, and Yong He^1,2,3、**

Author Affiliations

¹State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of China

²Liangzhu Laboratory, Zhejiang University, Hangzhou 310027, People’s Republic of China

³Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, College of Mechanical Engineering, Zhejiang University, Hangzhou 310027, People’s Republic of China

⁴Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou 310027, People’s Republic of China

⁵State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, People’s Republic of China

⁶Institute of Digital Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People’s Republic of China

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References(75)

[1] [1] Y. Li, J. Wu, C. He, H. He, M. Xie et al., 3D pre-stress bioprinting of directed tissues. Adv. Healthc. Mater. 12, e2301487 (2023). 10.1002/adhm.202301487

[2] [2] T. Su, M. Zhang, Q. Zeng, W. Pan, Y. Huang et al., Mussel-inspired agarose hydrogel scaffolds for skin tissue engineering. Bioact. Mater. 6, 579–588 (2020). 10.1016/j.bioactmat.2020.09.004

[3] [3] J. Chen, B. Wang, J.S. Caserto, K. Shariati, P. Cao et al., Sustained delivery of SARS-CoV-2 RBD subunit vaccine using a high affinity injectable hydrogel scaffold. Adv. Healthc. Mater. 11, e2101714 (2022). 10.1002/adhm.202101714

[4] [4] Q. Li, S. Xu, Q. Feng, Q. Dai, L. Yao et al., 3D printed silk-gelatin hydrogel scaffold with different porous structure and cell seeding strategy for cartilage regeneration. Bioact. Mater. 6, 3396–3410 (2021). 10.1016/j.bioactmat.2021.03.013

[5] [5] F. Yang, Y. Li, L. Wang, H. Che, X. Zhang et al., Full-thickness osteochondral defect repair using a biodegradable bilayered scaffold of porous zinc and chondroitin sulfate hydrogel. Bioact. Mater. 32, 400–414 (2023). 10.1016/j.bioactmat.2023.10.014

[6] [6] Q. Li, H. Yu, F. Zhao, C. Cao, T. Wu et al., 3D printing of microenvironment-specific bioinspired and exosome-reinforced hydrogel scaffolds for efficient cartilage and subchondral bone regeneration. Adv. Sci. 10, e2303650 (2023). 10.1002/advs.202303650

[7] [7] Y. Miao, Y. Chen, J. Luo, X. Liu, Q. Yang et al., Black phosphorus nanosheets-enabled DNA hydrogel integrating 3D-printed scaffold for promoting vascularized bone regeneration. Bioact. Mater. 21, 97–109 (2022). 10.1016/j.bioactmat.2022.08.005

[8] [8] H. Su, Q. Li, D. Li, H. Li, Q. Feng et al., A versatile strategy to construct free-standing multi-furcated vessels and a complicated vascular network in heterogeneous porous scaffolds via combination of 3D printing and stimuli-responsive hydrogels. Mater. Horiz. 9, 2393–2407 (2022). 10.1039/d2mh00314g

[9] [9] S. Xiao, T. Zhao, J. Wang, C. Wang, J. Du et al., Gelatin methacrylate (GelMA)-based hydrogels for cell transplantation: an effective strategy for tissue engineering. Stem Cell Rev. Rep. 15, 664–679 (2019). 10.1007/s12015-019-09893-4

[10] [10] X. Ning, J. Huang, A. Yimuhan, N. Yuan, C. Chen et al., Research advances in mechanical properties and applications of dual network hydrogels. Int. J. Mol. Sci. 23, 15757 (2022). 10.3390/ijms232415757

[11] [11] D. Ji, J.M. Park, M.S. Oh, T.L. Nguyen, H. Shin et al., Superstrong, superstiff, and conductive alginate hydrogels. Nat. Commun. 13, 3019 (2022). 10.1038/s41467-022-30691-z

[12] [12] M.A. Gwak, B.M. Hong, J.M. Seok, S.A. Park, W.H. Park, Effect of tannic acid on the mechanical and adhesive properties of catechol-modified hyaluronic acid hydrogels. Int. J. Biol. Macromol. 191, 699–705 (2021). 10.1016/j.ijbiomac.2021.09.123

[13] [13] A.R. Osi, H. Zhang, J. Chen, Y. Zhou, R. Wang et al., Three-dimensional-printable thermo/photo-cross-linked methacrylated chitosan-gelatin hydrogel composites for tissue engineering. ACS Appl. Mater. Interfaces 13, 22902–22913 (2021). 10.1021/acsami.1c01321

[14] [14] J. He, Y. Sun, Q. Gao, C. He, K. Yao et al., Gelatin methacryloyl hydrogel, from standardization, performance, to biomedical application. Adv. Healthc. Mater. 12, e2300395 (2023). 10.1002/adhm.202300395

[15] [15] W. Wang, Y. Zhang, W. Liu, Bioinspired fabrication of high strength hydrogels from non-covalent interactions. Prog. Polym. Sci. 71, 1–25 (2017). 10.1016/j.progpolymsci.2017.04.001

[16] [16] S.E. Bakarich, M.I.H. Panhuis, S. Beirne, G.G. Wallace, G.M. Spinks, Extrusion printing of ionic–covalent entanglement hydrogels with high toughness. J. Mater. Chem. B 1, 4939–4946 (2013). 10.1039/C3TB21159B

[17] [17] J. Wen, Y. Wu, Y. Gao, Q. Su, Y. Liu et al., Nanofiber composite reinforced organohydrogels for multifunctional and wearable electronics. Nano-Micro Lett. 15, 174 (2023). 10.1007/s40820-023-01148-9

[18] [18] S. Lin, J. Liu, X. Liu, X. Zhao, Muscle-like fatigue-resistant hydrogels by mechanical training. Proc. Natl. Acad. Sci. U.S.A. 116, 10244–10249 (2019). 10.1073/pnas.1903019116

[19] [19] X. Dong, X. Guo, Q. Liu, Y. Zhao, H. Qi et al., Strong and tough conductive organo-hydrogels via freeze-casting assisted solution substitution. Adv. Funct. Mater. 32, 2203610 (2022). 10.1002/adfm.202203610

[20] [20] M. Hua, S. Wu, Y. Ma, Y. Zhao, Z. Chen et al., Strong tough hydrogels via the synergy of freeze-casting and salting out. Nature 590, 594–599 (2021). 10.1038/s41586-021-03212-z

[21] [21] W. Li, X. Wang, Z. Liu, X. Zou, Z. Shen et al., Nanoconfined polymerization limits crack propagation in hysteresis-free gels. Nat. Mater. 23, 131–138 (2024). 10.1038/s41563-023-01697-9

[22] [22] K. Chen, Q. Chen, T. Zong, S. Liu, X. Yang et al., Effect of directional stretching on properties of PVA-HA-PAA composite hydrogel. J. Bionic Eng. 18, 1202–1214 (2021). 10.1007/s42235-021-00095-8

[23] [23] S. Choi, J.R. Moon, N. Park, J. Im, Y.E. Kim et al., Bone-adhesive anisotropic tough hydrogel mimicking tendon enthesis. Adv. Mater. 35, e2206207 (2023). 10.1002/adma.202206207

[24] [24] S. Hong, D. Sycks, H.F. Chan, S. Lin, G.P. Lopez et al., 3D printing of highly stretchable and tough hydrogels into complex, cellularized structures. Adv. Mater. 27, 4035–4040 (2015). 10.1002/adma.201501099

[25] [25] F. Gao, Z. Xu, Q. Liang, H. Li, L. Peng et al., Osteochondral regeneration with 3D-printed biodegradable high-strength supramolecular polymer reinforced-gelatin hydrogel scaffolds. Adv. Sci. 6, 1900867 (2019). 10.1002/advs.201900867

[26] [26] Q. He, Y. Huang, S. Wang, Hofmeister effect-assisted one step fabrication of ductile and strong gelatin hydrogels. Adv. Funct. Mater. 28, 1705069 (2018). 10.1002/adfm.201705069

[27] [27] X. Yuan, Z. Zhu, P. Xia, Z. Wang, X. Zhao et al., Tough gelatin hydrogel for tissue engineering. Adv. Sci. 10, e2301665 (2023). 10.1002/advs.202301665

[28] [28] H. Chen, P. Shi, F. Fan, H. Chen, C. Wu et al., Hofmeister effect-assisted one step fabrication of fish gelatin hydrogels. LWT 121, 108973 (2020). 10.1016/j.lwt.2019.108973

[29] [29] L. Shao, Q. Gao, C. Xie, J. Fu, M. Xiang et al., Directly coaxial 3D bioprinting of large-scale vascularized tissue constructs. Biofabrication 12, 035014 (2020). 10.1088/1758-5090/ab7e76

[30] [30] I. Pepelanova, K. Kruppa, T. Scheper, A. Lavrentieva, Gelatin-methacryloyl (GelMA) hydrogels with defined degree of functionalization as a versatile toolkit for 3D cell culture and extrusion bioprinting. Bioengineering 5, 55 (2018). 10.3390/bioengineering5030055

[31] [31] S. Hinderer, S.L. Layland, K. Schenke-Layland, ECM and ECM-like materials—Biomaterials for applications in regenerative medicine and cancer therapy. Adv. Drug Deliv. Rev. 97, 260–269 (2016). 10.1016/j.addr.2015.11.019

[32] [32] M.A. Ahmed, H.A. Al-Kahtani, I. Jaswir, H. AbuTarboush, E.A. Ismail, Extraction and characterization of gelatin from camel skin (potential halal gelatin) and production of gelatin nanoparticles. Saudi J. Biol. Sci. 27, 1596–1601 (2020). 10.1016/j.sjbs.2020.03.022

[33] [33] S. Farris, J. Song, Q. Huang, Alternative reaction mechanism for the cross-linking of gelatin with glutaraldehyde. J. Agric. Food Chem. 58, 998–1003 (2010). 10.1021/jf9031603

[34] [34] Q. Ruan, W. Chen, M. Lv, R. Zhang, X. Luo et al., Influences of trypsin pretreatment on the structures, composition, and functional characteristics of skin gelatin of Tilapia, grass carp, and sea perch. Mar. Drugs 21, 423 (2023). 10.3390/md21080423

[35] [35] Y. Hua, S.W. Cui, Q. Wang, Y. Mine, V. Poysa, Heat induced gelling properties of soy protein isolates prepared from different defatted soybean flours. Food Res. Int. 38, 377–385 (2005). 10.1016/j.foodres.2004.10.006

[36] [36] H.-X. Zhou, X. Pang, Electrostatic interactions in protein structure, folding, binding, and condensation. Chem. Rev. 118, 1691–2174 (2018). 10.1021/acs.chemrev.7b00305

[37] [37] W. Chang-Sheng, Q.I. Xue-Jie, M.A. Ying-Ge, Y. Zhong-Zhi, Theoretical study on the hydrogen bond strength in polypeptide molecules. Chem. J. Chin. Univ. 25, 1111 (2004)

[38] [38] M. te Vrugt, H. Löwen, R. Wittkowski, Classical dynamical density functional theory: from fundamentals to applications. Adv. Phys. 69, 121–247 (2020). 10.1080/00018732.2020.1854965

[39] [39] W. Zhao, H. Zhou, W. Li, M. Chen, M. Zhou et al., An environment-tolerant ion-conducting double-network composite hydrogel for high-performance flexible electronic devices. Nano-Micro Lett. 16, 99 (2024). 10.1007/s40820-023-01311-2

[40] [40] S. Wu, M. Hua, Y. Alsaid, Y. Du, Y. Ma et al., Poly(vinyl alcohol) hydrogels with broad-range tunable mechanical properties via the hofmeister effect. Adv. Mater. 33, e2007829 (2021). 10.1002/adma.202007829

[41] [41] C. Lindskog, J. Linné, L. Fagerberg, B.M. Hallström, C.J. Sundberg et al., The human cardiac and skeletal muscle proteomes defined by transcriptomics and antibody-based profiling. BMC Genomics 16, 475 (2015). 10.1186/s12864-015-1686-y

[42] [42] G. Singh, A. Chanda, Mechanical properties of whole-body soft human tissues: a review. Biomed. Mater. 16, 062004 (2021). 10.1088/1748-605x/ac2b7a

[43] [43] Y. Chen, Y. Zhou, Z. Hu, W. Lu, Z. Li et al., Gelatin-based metamaterial hydrogel films with high conformality for ultra-soft tissue monitoring. Nano-Micro Lett. 16, 34 (2023). 10.1007/s40820-023-01225-z

[44] [44] G. Yan, S. He, G. Chen, S. Ma, A. Zeng et al., Highly flexible and broad-range mechanically tunable all-wood hydrogels with nanoscale channels via the hofmeister effect for human motion monitoring. Nano-Micro Lett. 14, 84 (2022). 10.1007/s40820-022-00827-3

[45] [45] Y. Zhang, S. Furyk, D.E. Bergbreiter, P.S. Cremer, Specific ion effects on the water solubility of macromolecules: PNIPAM and the Hofmeister series. J. Am. Chem. Soc. 127, 14505–14510 (2005). 10.1021/ja0546424

[46] [46] K.M. Herman, J.P. Heindel, S.S. Xantheas, The many-body expansion for aqueous systems revisited: III. Hofmeister ion–water interactions. Phys. Chem. Chem. Phys. 23, 11196–11210 (2021). 10.1039/d1cp00409c

[47] [47] P. Jungwirth, P.S. Cremer, Beyond hofmeister. Nat. Chem. 6, 261–263 (2014). 10.1038/nchem.1899

[48] [48] R. Yan, Y. Yan, J. Gong, J. Ma, Superb tough hydrogels based on macromolecule micelles as cross-linkers. Mater. Res. Express 6, 055322 (2019). 10.1088/2053-1591/ab0592

[49] [49] J. Zhang, Y. Hu, L. Zhang, J. Zhou, A. Lu, Transparent, ultra-stretching, tough, adhesive carboxyethyl chitin/polyacrylamide hydrogel toward high-performance soft electronics. Nano-Micro Lett. 15, 8 (2022). 10.1007/s40820-022-00980-9

[50] [50] H. Amani, H. Arzaghi, M. Bayandori, A.S. Dezfuli, H. Pazoki-Toroudi et al., Controlling cell behavior through the design of biomaterial surfaces: a focus on surface modification techniques. Adv. Mater. Interfaces 6, 1900572 (2019). 10.1002/admi.201900572

[51] [51] J.W. Nichol, S.T. Koshy, H. Bae, C.M. Hwang, S. Yamanlar et al., Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials 31, 5536–5544 (2010). 10.1016/j.biomaterials.2010.03.064

[52] [52] W.R. Frontera, J. Ochala, Skeletal muscle: a brief review of structure and function. Calcif. Tissue Int. 96, 183–195 (2015). 10.1007/s00223-014-9915-y

[53] [53] S. Jabre, W. Hleihel, C. Coirault, Nuclear mechanotransduction in skeletal muscle. Cells 10, 318 (2021). 10.3390/cells10020318

[54] [54] Y. Morimoto, H. Onoe, S. Takeuchi, Biohybrid robot powered by an antagonistic pair of skeletal muscle tissues. Sci. Robot. 3, eaat4440 (2018). 10.1126/scirobotics.aat4440

[55] [55] S. SenGupta, C.A. Parent, J.E. Bear, The principles of directed cell migration. Nat. Rev. Mol. Cell Biol. 22, 529–547 (2021). 10.1038/s41580-021-00366-6

[56] [56] T. Fan, S. Wang, Z. Jiang, S. Ji, W. Cao et al., Controllable assembly of skeletal muscle-like bundles through 3D bioprinting. Biofabrication 14, 015009 (2021). 10.1088/1758-5090/ac3aca

[57] [57] M.S. Kang, Y. Yu, R. Park, H.J. Heo, S.H. Lee et al., Highly aligned ternary nanofiber matrices loaded with MXene expedite regeneration of volumetric muscle loss. Nano-Micro Lett. 16, 73 (2024). 10.1007/s40820-023-01293-1

[58] [58] N. Liu, Y. Zhu, K. Yu, Z. Gu, S. Lv et al., Functional blood-brain barrier model with tight connected minitissue by liquid substrates culture. Adv. Healthc. Mater. 12, e2201984 (2023). 10.1002/adhm.202201984

[59] [59] H. Granzier, S. Labeit, Structure-function relations of the giant elastic protein titin in striated and smooth muscle cells. Muscle Nerve 36, 740–755 (2007). 10.1002/mus.20886

[60] [60] R.L. Lieber, B.I. Binder-Markey, Biochemical and structural basis of the passive mechanical properties of whole skeletal muscle. J. Physiol. 599, 3809–3823 (2021). 10.1113/JP280867

[61] [61] B.E. Pollot, C.R. Rathbone, J.C. Wenke, T. Guda, Natural polymeric hydrogel evaluation for skeletal muscle tissue engineering. J. Biomed. Mater. Res. B Appl. Biomater. 106, 672–679 (2018). 10.1002/jbm.b.33859

[62] [62] I. Eugenis, D. Wu, C. Hu, G. Chiang, N.F. Huang et al., Scalable macroporous hydrogels enhance stem cell treatment of volumetric muscle loss. Biomaterials 290, 121818 (2022). 10.1016/j.biomaterials.2022.121818

[63] [63] N. Narayanan, Z. Jia, K.H. Kim, L. Kuang, P. Lengemann et al., Biomimetic glycosaminoglycan-based scaffolds improve skeletal muscle regeneration in a Murine volumetric muscle loss model. Bioact. Mater. 6, 1201–1213 (2020). 10.1016/j.bioactmat.2020.10.012

[64] [64] Y. Jin, D. Shahriari, E.J. Jeon, S. Park, Y.S. Choi et al., Functional skeletal muscle regeneration with thermally drawn porous fibers and reprogrammed muscle progenitors for volumetric muscle injury. Adv. Mater. 33, e2007946 (2021). 10.1002/adma.202007946

[65] [65] M.M. Carleton, M. Locke, M.V. Sefton, Methacrylic acid-based hydrogels enhance skeletal muscle regeneration after volumetric muscle loss in mice. Biomaterials 275, 120909 (2021). 10.1016/j.biomaterials.2021.120909

[66] [66] A. Mostafavi, M. Samandari, M. Karvar, M. Ghovvati, Y. Endo et al., Colloidal multiscale porous adhesive (bio)inks facilitate scaffold integration. Appl. Phys. Rev. 8, 041415 (2021). 10.1063/5.0062823

[67] [67] A. Behre, J.W. Tashman, C. Dikyol, D.J. Shiwarski, R.J. Crum et al., 3D bioprinted patient-specific extracellular matrix scaffolds for soft tissue defects. Adv. Healthc. Mater. 11, e2200866 (2022). 10.1002/adhm.202200866

[68] [68] Y. Qin, G. Ge, P. Yang, L. Wang, Y. Qiao et al., An update on adipose-derived stem cells for regenerative medicine: where challenge meets opportunity. Adv. Sci. 10, e2207334 (2023). 10.1002/advs.202207334

[69] [69] S.L. McNamara, B.R. Seo, B.R. Freedman, E.B. Roloson, J.T. Alvarez, C.T. O’Neill, D.J. Mooney, Anti-inflammatory therapy enables robot-actuated regeneration of aged muscle. Sci. Robot. 8(76), eadd9369 (2023). 10.1126/scirobotics.add9369

[70] [70] Z. Zhang, X. Zhao, C. Wang, Y. Huang, Y. Han et al., Injectable conductive micro-cryogel as a muscle stem cell carrier improves myogenic proliferation, differentiation and in situ skeletal muscle regeneration. Acta Biomater. 151, 197–209 (2022). 10.1016/j.actbio.2022.08.036

[71] [71] B.T. Corona, X. Wu, C.L. Ward, J.S. McDaniel, C.R. Rathbone et al., The promotion of a functional fibrosis in skeletal muscle with volumetric muscle loss injury following the transplantation of muscle-ECM. Biomaterials 34, 3324–3335 (2013). 10.1016/j.biomaterials.2013.01.061

[72] [72] I. Eugenis, D. Wu, T.A. Rando, Cells, scaffolds, and bioactive factors: Engineering strategies for improving regeneration following volumetric muscle loss. Biomaterials 278, 121173 (2021). 10.1016/j.biomaterials.2021.121173

[73] [73] J. Li, X. Liu, W. Tao, Y. Li, Y. Du et al., Micropatterned composite membrane guides oriented cell growth and vascularization for accelerating wound healing. Regen. Biomater. 10, rbac108 (2022). 10.1093/rb/rbac108

[74] [74] X. Han, Q. Saiding, X. Cai, Y. Xiao, P. Wang et al., Intelligent vascularized 3D/4D/5D/6D-printed tissue scaffolds. Nano-Micro Lett. 15, 239 (2023). 10.1007/s40820-023-01187-2

[75] [75] J. Gilbert-Honick, W. Grayson, Vascularized and innervated skeletal muscle tissue engineering. Adv. Healthc. Mater. 9, e1900626 (2020). 10.1002/adhm.201900626

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Ke Yao, Gaoying Hong, Ximin Yuan, Weicheng Kong, Pengcheng Xia, Yuanrong Li, Yuewei Chen, Nian Liu, Jing He, Jue Shi, Zihe Hu, Yanyan Zhou, Zhijian Xie, Yong He. 3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration[J]. Nano-Micro Letters, 2025, 17(1): 027

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Paper Information

Category: Research Articles

Received: Jun. 5, 2024

Accepted: Sep. 1, 2024

Published Online: Feb. 12, 2025

The Author Email: Xie Zhijian (xzj66@zju.edu.cn), He Yong (yongqin@zju.edu.cn)

DOI:10.1007/s40820-024-01524-z

Topics

laser devices and laser physics

Lasers and Laser Optics

Laser physics

laser manufacturing

Instrumentation, Measurement and Metrology