Dataset Information

Cartilage repair mediated by thermosensitive photocrosslinkable TGF?1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis.

ABSTRACT: Repairing cartilage defects using thermosensitive hydrogels is an attractive treatment strategy, but the poor mechanical properties and limited understanding of the interactions between hydrogels and cells limit their application. Methods: In this study, a thermosensitive hydroxypropyl chitin hydrogel (HPCH) was functionalized with methacrylate groups to synthesize photocrosslinkable glycidyl methacrylate-modified HPCH (GM-HPCH). GM-HPCH could form a gel in situ through a thermosensitive sol-gel transition and its mechanical properties can be improved by UV irradiation. Cell viability, cell adhesion and anti-apoptosis activity of GM-HPCH were evaluated. Transforming growth factor-?1 (TGF?1) was introduced into the GM-HPCH hydrogel to fabricate the composite hydrogel. The macrophage immunomodulation, MSC recruitment and chondrogenesis of the composite hydrogel were evaluated. Results: With high biocompatibility, GM-HPCH could protect chondrocytes from apoptosis. Both the in vitro and in vivo experiments showed that GM-HPCH + TGF?1 shifted the recruited macrophages from M1 to M2 and promoted chondrogenic gene expression. Additionally, the composite hydrogel could promote the migration of marrow stromal cells (MSCs) in the Transwell test and increase migrated gene expression. The fluorescent tracking of MSCs confirmed MSC homing in the rat chondral defect with the help of GM-HPCH. The macroscopic evaluation and histological results at 6 weeks and 12 weeks postsurgery showed that GM-HPCH + TGF?1 can achieve superior cartilage healing. Conclusions: The GM-HPCH + TGF?1 hydrogel effectively promoted cartilage repair via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis; thus it is a promising injectable hydrogel for cartilage regeneration.

SUBMITTER: Ji X

PROVIDER: S-EPMC7052899 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis.

Ji Xiongfa X Lei Zehua Z Yuan Meng M Zhu Hao H Yuan Xi X Liu Wenbin W Pu Hongxu H Jiang Jiawei J Zhang Yu Y Jiang Xulin X Xiao Jun J

Theranostics 20200203 6

Repairing cartilage defects using thermosensitive hydrogels is an attractive treatment strategy, but the poor mechanical properties and limited understanding of the interactions between hydrogels and cells limit their application. <b>Methods</b>: In this study, a thermosensitive hydroxypropyl chitin hydrogel (HPCH) was functionalized with methacrylate groups to synthesize photocrosslinkable glycidyl methacrylate-modified HPCH (GM-HPCH). GM-HPCH could form a gel <i>in situ</i> through a thermosen ...[more]

PMID: 32194841

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Project description:Because of the superior characteristics of photocrosslinkable hydrogels suitable for 3D cell-laden bioprinting, tissue regeneration based on photocrosslinkable hydrogels has become an important research topic. However, due to nutrient permeation obstacles caused by the dense networks and static culture conditions, there have been no successful reports on in vitro cartilage regeneration with certain thicknesses based on photocrosslinkable hydrogels. To solve this problem, hydrostatic pressure (HP) provided by the bioreactor was used to regulate the in vitro cartilage regeneration based on hybrid photocrosslinkable (HPC) hydrogel. Chondrocyte laden HPC hydrogels (CHPC) were cultured under 5 MPa HP for 8 weeks and evaluated by various staining and quantitative methods. Results demonstrated that CHPC can maintain the characteristics of HPC hydrogels and is suitable for 3D cell-laden bioprinting. However, HPC hydrogels with concentrations over 3% wt% significantly influenced cell viability and in vitro cartilage regeneration due to nutrient permeation obstacles. Fortunately, HP completely reversed the negative influences of HPC hydrogels at 3% wt%, significantly enhanced cell viability, proliferation, and extracellular matrix (ECM) deposition by improving nutrient transportation and up-regulating the expression of cartilage-specific genes, and successfully regenerated homogeneous cartilage with a thickness over 3 mm. The transcriptome sequencing results demonstrated that HP regulated in vitro cartilage regeneration primarily by inhibiting cell senescence and apoptosis, promoting ECM synthesis, suppressing ECM catabolism, and ECM structure remodeling. Evaluation of in vivo fate indicated that in vitro regenerated cartilage in the HP group further developed after implantation and formed homogeneous and mature cartilage close to the native one, suggesting significant clinical potential. The current study outlines an efficient strategy for in vitro cartilage regeneration based on photocrosslinkable hydrogel scaffolds and its in vivo application.

Dataset Information

Cartilage repair mediated by thermosensitive photocrosslinkable TGF?1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis.

Publications

Cartilage repair mediated by thermosensitive photocrosslinkable TGFβ1-loaded GM-HPCH via immunomodulating macrophages, recruiting MSCs and promoting chondrogenesis.

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