Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release

Kuan ZHANG; Jielai YANG; Yulong SUN; Yi WANG; Jing LIANG; Jing LUO; Wenguo CUI; Lianfu DENG; Xiangyang XU; Bo WANG; Hongyu ZHANG

doi:10.1007/s40544-020-0437-5

Friction 2022, 10(2): 232-246 https://doi.org/10.1007/s40544-020-0437-5

Research Article |

Open Access | Issue | Published: 11 January 2021

Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release

Show Author's Information Hide Author's Information Kuan ZHANG^{¹^,²^,^†}, Jielai YANG^{³^,⁴^,^†}, Yulong SUN^¹, Yi WANG^¹, Jing LIANG^⁴, Jing LUO^⁵, Wenguo CUI^⁴, Lianfu DENG^⁴, Xiangyang XU^³(

), Bo WANG^²(

), Hongyu ZHANG^¹(

)

1 State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China

2 School of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China

3 Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

4 Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

5 Beijing Research Institute of Automation for Machinery Industry Co., Ltd., Beijing 100120, China

^† Kuan ZHANG and Jielai YANG contributed equally to this work.

Keywords:

articular cartilage, hydration lubrication, drug delivery, hydrogel, zwitterionic polymer

Cite this article:

ZHANG K, YANG J, SUN Y, et al. Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release. Friction, 2022, 10(2): 232-246. https://doi.org/10.1007/s40544-020-0437-5

Download citation

EndNote(RIS)

BibTeX

682

Views

Downloads

Citations

Crossref

WoS

Scopus

CSCD

Abstract Full text About this article

Abstract

The occurrence of osteoarthritis is closely related to progressive and irreversible destruction of the articular cartilage, which increases the friction significantly and causes further inflammation of the joint. Thus, a scaffold for articular cartilage defects should be developed via lubrication restoration and drug intervention. In this study, we successfully synthesized gelatin-based composite hydrogels, namely GelMA-PAM-PMPC, with the properties of biomimetic lubrication and sustained drug release by photopolymerization of methacrylic anhydride modified gelatin (GelMA), acrylamide (AM), and 2-methacryloyloxyethyl phosphorylcholine (MPC). Tribological test showed that the composite hydrogels remarkably enhanced lubrication due to the hydration lubrication mechanism, where a tenacious hydration shell was formed around the zwitterionic phosphocholine headgroups. In addition, drug release test indicated that the composite hydrogels efficiently encapsulated an anti-inflammatory drug (diclofenac sodium) and achieved sustained release. Furthermore, the in vitro test revealed that the composite hydrogels were biocompatible, and the mRNA expression of both anabolic and catabolic genes of the articular cartilage was suitably regulated. This indicated that the composite hydrogels could effectively protect chondrocytes from inflammatory cytokine-induced degeneration. In summary, the composite hydrogels that provide biomimetic hydration lubrication and sustained local drug release represent a promising scaffold for cartilage defects in the treatment of osteoarthritis.

Full text

Abstract

Full text

Outline

About this article

Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release

Show Author's information Hide Author's Information Kuan ZHANG^{¹^,²^,^†}, Jielai YANG^{³^,⁴^,^†}, Yulong SUN^¹, Yi WANG^¹, Jing LIANG^⁴, Jing LUO^⁵, Wenguo CUI^⁴, Lianfu DENG^⁴, Xiangyang XU^³(

), Bo WANG^²(

), Hongyu ZHANG^¹(

)

1 State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China

2 School of Chemical and Biological Engineering, Shandong University of Science and Technology, Qingdao 266590, China

3 Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

5 Beijing Research Institute of Automation for Machinery Industry Co., Ltd., Beijing 100120, China

^† Kuan ZHANG and Jielai YANG contributed equally to this work.

Abstract

Keywords: articular cartilage, hydration lubrication, drug delivery, hydrogel, zwitterionic polymer

References(42)

[1]

Ji X, Yan Y, Sun T, Zhang Q, Wang Y, Zhang M, Zhang H, Zhao X. Glucosamine sulphate-loaded distearoyl phosphocholine liposomes for osteoarthritis treatment: combination of sustained drug release and improved lubrication. Biomater Sci 7: 2716-2728 (2019)

DOI Google Scholar

[2]

Zheng Y, Yang J, Liang J, Xu X, Cui W, Deng L, Zhang H. Bioinspired hyaluronic acid/phosphorylcholine polymer with enhanced lubrication and anti-inflammation. Biomacromolecules 20: 4135-4142 (2019)

DOI Google Scholar

[3]

Wan L, Wang Y, Tang X, Sun Y, Luo J, Zhang H. Biodegradable lubricating mesoporous silica nanoparticles for osteoarthritis therapy. Friction 10(1): 68-79 (2022)

DOI Google Scholar

[4]

Tan X, Sun Y, Sun T, Zhang H. Mechanised lubricating silica nanoparticles for on-command cargo release on simulated surfaces of joint cavities. Chem Commun 55: 2593-2596 (2019)

DOI Google Scholar

[5]

Pan Y, Xiao C, Tan H, Yuan G, Li J, Li S, Jia Y, Xiong D, Hu X, Niu X. Covalently injectable chitosan/chondroitin sulfate hydrogel integrated gelatin/heparin microspheres for soft tissue engineering. Int J Polym Mater 70: 149-157 (2021)

DOI Google Scholar

[6]

Wang M, Chen J, Li W, Zang F, Liu X, Qin S. Paclitaxel- nanoparticles-loaded double network hydrogel for local treatment of breast cancer after surgical resection. Mater Sci Eng C Mater Biol Appl 114: 111046 (2020)

DOI Google Scholar

[7]

Liu Y, Xiong D. Self-healable polyacrylic acid-polyacrylamide- ferric ion dual-crosslinked hydrogel with good biotribological performance as a load-bearing surface. J Appl Polym Sci 137: 48499 (2019)

DOI Google Scholar

[8]

Chen K, Chen G, Wei S, Yang X, Zhang D, Xu L. Preparation and property of high strength and low friction PVA-HA/PAA composite hydrogel using annealing treatment. Mater Sci Eng C Mater Biol Appl 91: 579-588 (2018)

DOI Google Scholar

[9]

Gong J, Katsuyama Y, Kurokawa T, Osada Y. Double- network hydrogels with extremely high mechanical strength. Adv Mater 15: 1155-1158 (2003)

DOI Google Scholar

[10]

Han L, Liu K, Wang M, Wang K, Fang L, Chen H, Zhou J, Lu X. Mussel-inspired adhesive and conductive hydrogel with long-lasting moisture and extreme temperature tolerance. Adv Funct Mater 28: 1704195 (2018)

DOI Google Scholar

[11]

Gan D, Xu T, Xing W, Ge X, Fang L, Wang K, Ren F, Lu X. Mussel-inspired contact-active antibacterial hydrogel with high cell affinity, toughness, and recoverability. Adv Funct Mater 29: 1805964 (2019)

DOI Google Scholar

[12]

Liu K, Han L, Tang P, Yang K, Gan D, Wang X, Wang K, Ren F, Fang L, Xu X, et al. An anisotropic hydrogel based on mussel-inspired conductive ferrofluid composed of electromagnetic nanohybrids. Nano Lett 19: 8343-8356 (2019)

DOI Google Scholar

[13]

Wang J, Lin L, Cheng Q, Jiang L. A strong bio-inspired layered pnipam-clay nanocomposite hydrogel. Angew Chem Int Ed 51: 4676-4680 (2012)

DOI Google Scholar

[14]

Dai X, Zhang Y, Gao L, Bai T, Wang W, Cui Y, Liu W. A mechanically strong, highly stable, thermoplastic, and self- healable supramolecular polymer hydrogel. Adv Mater 27: 3566-3571 (2015)

DOI Google Scholar

[15]

Wang H, Zhou L, Liao J, Ning C, Tan G. Cell-laden photocrosslinked gelma-dexma copolymer hydrogels with tunable mechanical properties for tissue engineering. J Mater Sci Mater Med 25: 2173-2183 (2014)

DOI Google Scholar

[16]

Visser J, Gawlitta D, Benders K E, Malda J. Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles. Biomaterials 37: 174-182 (2015)

DOI Google Scholar

[17]

Yue K, Santiago G T, Alvarez M M, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (gelma) hydrogels. Biomaterials 73: 254-271 (2015)

DOI Google Scholar

[18]

Elomaa L, Keshi E, Sauer I M, Weinhart M. Development of GelMA/PCL and dECM/PCL resins for 3D printing of acellular in vitro tissue scaffolds by stereolithography. Mater Sci Eng C Mater Biol Appl 112: 110958 (2020)

DOI Google Scholar

[19]

Su R, Zihlmann C, Akbari M, Tang X, Khademhosseini A. Reduced graphene oxide-gelma hybrid hydrogels as scaffolds for cardiac tissue engineering. Small 12: 3677-3689 (2016)

DOI Google Scholar

[20]

Yuk H, Zhang T, Lin S, Parada G A, Zhao X. Tough bonding of hydrogels to diverse non-porous surfaces. Nat Mater 15: 190-196 (2016)

DOI Google Scholar

[21]

Hu X, Vatankhah-Varnoosfaderani M, Zhou J, Li Q, Sheiko S S. Weak hydrogen bonding enables hard, strong, tough, and elastic hydrogels. Adv Mater 27: 6899-6905 (2016)

DOI Google Scholar

[22]

Jahn S, Seror J, Klein J. Lubrication of articular cartilage. Annu Rev Biomed Eng 18: 235-258 (2016)

DOI Google Scholar

[23]

Seror J, Merkher Y, Kampf N, Collinson L, Day A J, Maroudas A, Klein J. Normal and shear interactions between hyaluronan-aggrecan complexes mimicking possible boundary lubricants in articular cartilage in synovial joints. Biomacromolecules 13: 3823-3832 (2012)

DOI Google Scholar

[24]

Wang Y, Sun Y, Gu Y, Zhang H. Articular cartilage-inspired surface functionalization for enhanced lubrication. Adv Mater Interfaces 6: 1900180 (2019)

DOI Google Scholar

[25]

Klein J. Hydration lubrication. Friction 1: 1-23 (2013)

DOI Google Scholar

[26]

Moro T, Takatori Y, Ishihara K, Konno T, Takigawa Y, Matsushita T, Chung U, Nakamura K, Kawaguchi H. Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis. Nat Mater 3: 829-836 (2004)

DOI Google Scholar

[27]

Kyomoto M, Moro T, Saiga K, Miyaji F, Kawaguchi H, Takatori Y, Nakamura K, Ishihara K. Lubricity and stability of poly(2-methacryloyloxyethyl phosphorylcholine) polymer layer on Co-Cr-Mo surface for hemi-arthroplasty to prevent degeneration of articular cartilage. Biomaterials 31: 658-668 (2010)

DOI Google Scholar

[28]

Kyomoto M, Moro T, Yamane S, Hashimoto M, Takatori Y, Ishihara K. Poly(ether-ether-ketone) orthopedic bearing surface modified byself-initiated surface grafting of poly(2- methacryloyloxyethyl phosphorylcholine). Biomaterials 34: 7829-7839 (2013)

DOI Google Scholar

[29]

Daniele M A, Adams A A, Naciri J, North S H, Ligler F S. Interpenetrating networks based on gelatin methacrylamide and PEG formed using concurrent thiol click chemistries for hydrogel tissue engineering scaffolds. Biomaterials 35: 1845-1856 (2014)

DOI Google Scholar

[30]

Liu B, Wang Y, Miao Y, Zhang X, Fan Z, Singh G, Zhang X, Xu K, Li B, Hu Z, et al. Hydrogen bonds autonomously powered gelatin methacrylate hydrogels with super-elasticity, self-heal and underwater self-adhesion for sutureless skin and stomach surgery and E-skin. Biomaterials 171: 83-96 (2018)

DOI Google Scholar

[31]

Brown L, Zhang H, Blunt L, Barrans S. Reproduction of fretting wear at the stem-cement interface in total hip replacement. Proc Inst Mech Eng Part H-J Eng Med 221: 963-971 (2007)

DOI Google Scholar

[32]

Zhang H, Zhang S, Luo J, Liu Y, Qian S, Liang F, Huang Y. Investigation of protein adsorption mechanism and biotribological properties at simulated stem-cement interface. J Tribol-Trans ASME 135: 032301 (2013)

DOI Google Scholar

[33]

Livak K J, Schmittgen T D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25: 402-408 (2001)

DOI Google Scholar

[34]

Yan Y, Sun T, Zhang H, Ji X, Sun Y, Zhao X, Deng L, Jin Q, Cui W, Santos H, et al. Euryale ferox seed-inspired superlubricated nanoparticles for treatment of osteoarthritis. Adv Funct Mater 29: 1807559 (2019)

DOI Google Scholar

[35]

Lin P, Zhang R, Wang X, Zhou F. Articular cartilage inspired bilayer tough hydrogel prepared by interfacial modulated polymerization showing excellent combination of high load-bearing and low friction performance. ACS Macro Lett 5: 1191-1195 (2016)

DOI Google Scholar

[36]

Shoaib T, Heintz J, Lopez-Berganza J A, Muro-Barrios R, Egner S A, Espinosa-Marzal R. Stick-slip friction reveals hydrogel lubrication mechanisms. Langmuir 34: 756-765 (2018)

DOI Google Scholar

[37]

Gombert Y, Simic R, Roncoroni F, Dubner M, Geue T, Spencer N D. Structuring hydrogel surfaces for tribology. Adv Mater Interfaces 6: 1901320 (2019)

DOI Google Scholar

[38]

Zhang X, Wang J, Jin H, Wang S, Song W. Bioinspired supramolecular lubricating hydrogel induced by shear force. J Am Chem Soc 140: 3186-3189 (2018)

DOI Google Scholar

[39]

Liu G, Cai M, Zhou F, Liu W. Charged polymer brushes- grafted hollow silica nanoparticles as a novel promising material for simultaneous joint lubrication and treatment. J Phys Chem B 118: 4920-4931 (2014)

DOI Google Scholar

[40]

Chen H, Sun T, Yan Y, Ji X, Sun Y, Zhao X, Qi J, Cui W, Deng L, Zhang H. Cartilage matrix-inspired biomimetic superlubricated nanospheres for treatment of osteoarthritis. Biomaterials 242: 119931 (2020)

DOI Google Scholar

[41]

Seror J, Zhu L, Goldberg R, Day A J, Klein J. Supramolecular synergy in the boundary lubrication of synovial joints. Nat Commun 6: 6497 (2015)

DOI Google Scholar

[42]

Ma S, Scaraggi M, Wang D, Zhou F. Stick-slip friction reveals hydrogel lubrication mechanisms. Adv Func Mater 25: 7366-7374 (2016)

DOI Google Scholar

About this article

Publication history

Acknowledgements

Rights and permissions

Publication history

Received: 12 June 2020

Revised: 27 July 2020

Accepted: 30 July 2020

Published: 11 January 2021

Issue date: February 2022

Copyright

Acknowledgements

This study was ﬁnancially supported by the National Natural Science Foundation of China (Nos. 51675296, 21868011, and 81772372), Shanghai Municipal Science Foundation (No. SYXF011803), Tsinghua University- Peking Union Medical College Hospital Initiative Scientific Research Program (No. 20191080593), the National Key R&D Program of China (No. 2017YFC1103800), Foshan-Tsinghua Innovation Special Fund (FTISF), Research Fund of State Key Laboratory of Tribology, Tsinghua University, China (No. SKLT2020C11), and Ng Teng Fong Charitable Foundation (No. 202-276-132-13).

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.