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Bioactive Materials · 2020 · IF 8.724

Hierarchical macro-microporous WPU-ECM scaffolds combined with Microfracture Promote in Situ Articular Cartilage Regeneration in Rabbits

Mingxue Chen,YangYang Li,Shuyun Liu,Zhaoxuan Feng,Hao Wang,Dejin Yang,Weimin Guo,Zhiguo Yuan,Shuang Gao,Yu Zhang,Kangkang Zha,Bo Huang,Fu Wei,Xinyu Sang,Qinyu Tian,Xuan Yang,Xiang sui,Yixin Zhou,Yufeng Zheng,Quanyi Guo

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro‐microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro‐microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro‐microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro‐microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.

研究领域: 组织工程学 · 再生医学
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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

Cartilage-targeting mRNA-lipid nanoparticles rescue perifocal apoptotic chondrocytes for integrative cartilage repair

Xinning Yu,Tengjing Xu,Huimin Shi,Jianqiao Hong,Xiaoqiang Jin,Le Cao,Jiajie Wang,Yunting Lin,Zongyou Pan,Siheng Wang,Jinghua Fang,Kaiwang Xu,Hongyun Song,Zhuxing Zhou,Sunan Zhu,Jun Yin,Yiying Qi,Xuesong Dai

Integration of repair tissue with host cartilage is challenging. The persistent and drastic hypocellular interface resulting from perifocal chondrocyte apoptosis, leads to failure of cartilage repair over time. Recombinant insulin-like growth factor-1 (IGF-1) has been shown to inhibit chondrocyte apoptosis in vitro. However, low bioactivity, limited penetration and short retention are its drawbacks. Herein, a cartilage targeting ionizable lipid nanoparticle (LNP) is developed. Messenger RNA (mRNA) encoding IGF-1 is chemically modified and encapsulated by LNP (mRNA-LNP). CAQK, a peptide previously used for targeted delivery to the central nervous system, is introduced to mRNA-LNP (mRNA-cLNP) to bind aggrecan enriched in cartilage. As a result, mRNA-cLNP exhibits improved penetration of cartilage and prolonged retention in the joint cavity. The mRNA-cLNP also showed robust reversal of chondrocyte apoptosis. In a full-thickness chondral defect plus microfracture model, mRNA-cLNP maintained interfacial cellularity and prevented matrix degradation in cartilage-cartilage interface. This study shows that mRNA-cLNP is a promising therapeutic agent for integrative cartilage repair.

研究领域: 骨科 · 生物医学工程 · 组织工程
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Bioactive Materials · 2025 · IF 20.3

Hyaluronan regulates the assembly structure and biofunction of polycationic silk fibroin to boost microfracture

Gong Li,Birui Yang,Zhulian Li,Peiyang Gu,Yaping Zou,Yuxiang Wang,Yujiang Fan,Yong Sun

Dysregulated inflammatory microenvironment and insufficient recruitment of functional cells/factors at the early stage limit the efficacy of microfracture (MF) therapy. Here, we regulated the assembly structure of functional polycationic silk fibroin (CSF) with sulfhydryl-modified hyaluronan (HS) to fabricate a cartilage repair patch (ECSF-HS-H), which achieved rapid hemostasis, recruitment of reparative cells/factors, and inflammation regulation. Through non-covalent/covalent interactions and β-sheet transitions, the assembly structure of CSF was reconfigured to adapt to the cyclic mechanical properties required under articular stress conditions while preserving inherent rapid hemostatic ability, reduce the potential inhibitory effect of cationic charges on cell proliferation, and enhance chondrogenic differentiation of stem cells. In a rabbit MF model, ECSF-HS-H demonstrated accelerated coagulation, reduced early inflammation in synovial fluid, promoted M2 macrophage polarization, and improved hyaline cartilage regeneration. This strategy of functional structural regulation at the molecular level offers a novel approach for developing protein-based scaffolds to enhance MF procedures.

CAS / MDL: 1898-66-4 819-83-0
研究领域: 生物医学工程 · 组织工程 · 再生医学 · 生物材料 · 分子组装
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MATERIALS & DESIGN · 2024 · IF 7.6

Hydroxypropyl Chitin-Oxidized chondroitin sulfate double-network hydrogel assists microfracture technique to enhance cartilage regeneration

Xi Yuan,Guanghao Li,Long Huang,Meng Zheng,Jin Su,Junlai Wan,Haozhe Cheng,Hao Zhu,Xulin Jiang,Jun Xiao

Cartilage has limited self-repair ability, leading to osteoarthritis postinjury and ultimately physical disability in people. In addition, cartilage injury is accompanied by loss of extracellular matrix (ECM) and infiltration of inflammation, which makes cartilage regeneration more difficult. In this study, a hybrid hydrogel of hydroxypropyl chitin and oxidized chondroitin sulfate (HPCH-OCS) with injectable and thermosensitive properties was prepared by a Schiff base reaction. In vitro , the HPCH-OCS hydrogel showed desirable biocompatibility and bioactivity by promoting chondrogenic differentiation of stem cells, maintaining the chondrocyte phenotype, and inhibiting proteins related to cartilage ECM catabolism under inflammatory conditions. In vivo , the HPCH-OCS hydrogel combined with microfracture could effectively repair cartilage defects and promote cartilage regeneration. In conclusion, the HPCH-OCS hydrogel has good biological and mechanical properties, and its combination with microfracture provides an effective strategy for clinical cartilage regeneration.

研究领域: 生物医学工程 · 组织工程 · 骨科 · 再生医学
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