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Friction  2022, Vol. 10 Issue (2): 232-246    doi: 10.1007/s40544-020-0437-5
Research Article     
Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release
Kuan ZHANG1,2,Jielai YANG3,4,Yulong SUN1,Yi WANG1,Jing LIANG4,Jing LUO5,Wenguo CUI4,Lianfu DENG4,Xiangyang XU3,*(),Bo WANG2,*(),Hongyu ZHANG1,*()
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
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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.

Key wordshydrogel      articular cartilage      zwitterionic polymer      hydration lubrication      drug delivery     
Received: 12 June 2020      Published: 17 January 2022
Fund:  National Natural Science Foundation of China(51675296);Shanghai Municipal Science Foundation(SYXF011803);Tsinghua University- Peking Union Medical College Hospital Initiative Scientific Research Program(20191080593);National Key R&D Program of China(2017YFC1103800);Foshan-Tsinghua Innovation Special Fund (FTISF), Research Fund of State Key Laboratory of Tribology, Tsinghua University, China(SKLT2020C11);Ng Teng Fong Charitable Foundation(202-276-132-13)
Corresponding Authors: Xiangyang XU,Bo WANG,Hongyu ZHANG     E-mail:;;
About author: Kuan ZHANG. He received his B.S. in chemical engineering and technology in 2016 from Hainan University. He is currently a joint master student in Tsinghua University. His research interests include biotribology and soft materials.|Jielai YANG. He is a Ph.D. student at Department of Orthopedics & Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine. His research focuses on the novel biomaterials for osteochondral regeneration and osteoarthritis management.|Xiangyang XU. He is director of foot and ankle surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. He is deputy director of foot and ankle surgery, Chinese Medical Association. He got his Ph.D. degree from Shanghai Medical University. His research focuses on diagnosis and treatment of diseases of the foot and ankle, with expertise in ankle instability and ankle osteoarthritis.|Bo WANG. He is a professor at College of Chemical and Biological Engineering, Shandong University of Science and Technology, China. He received his B.S. degree in Hainan University and Ph.D. degree in Zhejiang University, China. His research covers green chemistry, bio-catalysis, and asymmetric synthesis.|Hongyu ZHANG. He received his B.S. degree from Tianjin University, China (2005) and Ph.D. degree from University of Huddersfield, UK (2009). He is an associate professor at the State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, China. His research interests focus on the development of lubricating biomaterials such as nanoparticles, coatings, hydrogels, and electrospun nanofibers, which integrate the multi-disciplinary knowledge including biotribology, chemistry, materials science, and medicine to address clinical issues, e.g., osteoarthritis, anti-tissue/cell/ bacteria adhesion, bone tissue engineering, etc.
Cite this article:

Kuan ZHANG,Jielai YANG,Yulong SUN,Yi WANG,Jing LIANG,Jing LUO,Wenguo CUI,Lianfu DENG,Xiangyang XU,Bo WANG,Hongyu ZHANG. Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release. Friction, 2022, 10(2): 232-246.

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GenesForward sequenceReverse sequence
Table 1 The primer sequences of the genes used in the study.
Fig. 1 Schematic illustration of gelatin-based composite hydrogels for the treatment of osteoarthritis with biomimetic lubrication and sustained drug release. (a) Synthesis of the composite hydrogels through photopolymerization. (b) Lubrication enhancement and chondroprotective potential of the hydrogels.
Fig. 2 Characterization of the composite hydrogels. 1H NMR spectrum of (a) gelatin and (b) GelMA. (c) FTIR spectrum of PMPC, GelMA, and GelMA-PAM-PMPC. (d) TGA curve, (e) relative volume, (f) swelling ratio of GelMA and GelMA-PAM-PMPC. Water contact angle, SEM image, pore distribution, EDS spectrum of (g, i, k, m) GelMA and (h, j, l, n) GelMA-PAM-PMPC. (o) Compression stress, and (p) drug release profile of GelMA and GelMA-PAM-PMPC.
Fig. 3 Lubrication property of composite hydrogels. (a) Schematic diagram showing the setup of the tribological test. Surface topography contour of (b) GelMA-PAM and (c) GelMA-PAM-PMPC. (d) COF of GelMA-PAM-PMPC with different MPC contents. COF of GelMA-PAM and GelMA-PAM-PMPC with (e) various normal loads, rotation frequency: 5 Hz and (f) various rotation frequencies, normal load: 0.5 N. (g) Schematic diagram showing the deformation of the hydrogels under applied normal load. Surface topography contour of (h) steel ball and (i) PDMS ball. COF-cycle curve for (j) steel contact pair and (k) PDMS contact pair. Inset figure shows the average COF calculated from different cycle intervals.
Fig. 4  In vitro cell viability and proliferation of the chondrocytes incubated with the GelMA and GelMA-PAM-PMPC hydrogels for 1, 3, and 5 days. Blank group: untreated chondrocytes. (a) Representative fluorescence images of the chondrocytes in live/dead cell staining assay. (b, c) Quantitative data of the (b) live and (c) dead cells summarized from the live/dead cell staining assay. (d) Phalloidin staining showing the fibrous actin of the cytoskeleton of the cells. (e) Cell cytotoxicity of the hydrogels examined with CCK-8 assay. The hydrogels are biocompatible with the chondrocytes. NS: no significance.
Fig. 5 RT-qPCR analysis showing the mRNA expression levels of anabolic genes (a, e) Aggrecan, (b, f) COL2A1, and catabolic genes (c, g) MMP13, (d, h) ADAMTS5 in IL-1β and TNF-α treated chondrocytes, which are incubated with the GelMA and GelMA-PAM-PMPC hydrogels. n = 3, *P < 0.05, **P < 0.01, compared with the blank group.
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