Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis: Toward a precision therapy

Liu, Weixuan; Liu, Anqi; Li, Xujun; Sun, Ziyang; Sun, Zhuo; Liu, Yaru; Wang, Gang; Huang, Dan; Xiong, Hao; Yu, Shiyong; Zhang, Xintao; Fan, Cunyi

doi:10.1016/j.bioactmat.2023.06.012

Cited by 6 publications

(5 citation statements)

References 59 publications

(63 reference statements)

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“…Recently, accumulating evidence has indicated that targeted delivery of biologicals toward chondrocytes appears to be a promising strategy for osteoarthritis treatment, and there has been a surge in interest surrounding a diverse range of peptides that exhibit specific affinity to cartilage components [ 41 ]. Based on this, WY was grafted onto liposomes to develop a more efficient delivery of UA to chondrocytes in this study.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

Chen,

Yang,

Cai

et al. 2024

Research

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Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

Chen,

Yang,

Cai

et al. 2024

Research

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“…These innovative engineering approaches substan- tially mitigated OA via negative regulation of NLRP3 inflammasome activation and inhibition of chondrocyte pyroptosis. 119 In addition to genetic engineering, preconditioning holds great promise for optimizing the therapeutic effect of EV-based NPs. 120 Hypoxia preconditioning has been reported to exert an amplified therapeutic effect of MSC EVs on cartilage regeneration and inflammation inhibition, which has demonstrated clear superiority over that of the normoxia counterpart.…”

Section: Nano Delivery Systems For Cartilage Repairmentioning

confidence: 99%

“…They were also modified with the Col2-targeting peptide through genetic engineering techniques. These innovative engineering approaches substantially mitigated OA via negative regulation of NLRP3 inflammasome activation and inhibition of chondrocyte pyroptosis . In addition to genetic engineering, preconditioning holds great promise for optimizing the therapeutic effect of EV-based NPs .…”

Section: Nano Delivery Systems For Cartilage Repairmentioning

confidence: 99%

Harnessing Nanomedicine for Cartilage Repair: Design Considerations and Recent Advances in Biomaterials

Zhou,

Zhang,

et al. 2024

ACS Nano

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Cartilage injuries are escalating worldwide, particularly in aging society. Given its limited self-healing ability, the repair and regeneration of damaged articular cartilage remain formidable challenges. To address this issue, nanomaterials are leveraged to achieve desirable repair outcomes by enhancing mechanical properties, optimizing drug loading and bioavailability, enabling site-specific and targeted delivery, and orchestrating cell activities at the nanoscale. This review presents a comprehensive survey of recent research in nanomedicine for cartilage repair, with a primary focus on biomaterial design considerations and recent advances. The review commences with an introductory overview of the intricate cartilage microenvironment and further delves into key biomaterial design parameters crucial for treating cartilage damage, including microstructure, surface charge, and active targeting. The focal point of this review lies in recent advances in nano drug delivery systems and nanotechnology-enabled 3D matrices for cartilage repair. We discuss the compositions and properties of these nanomaterials and elucidate how these materials impact the regeneration of damaged cartilage. This review underscores the pivotal role of nanotechnology in improving the efficacy of biomaterials utilized for the treatment of cartilage damage.

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“…Research by Liu et al found that hUMSCs exos treat osteoarthritis by promoting the survival and anabolism of chondrocytes in an inflammatory environment, inhibiting inflammation, inhibiting cartilage degradation, and upregulating proteoglycans, Col II, etc [35]. Mesenchymal stem cells (MSC) exos regulate chondrocyte function through adenosinemediated activation of the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways.…”

Section: In Vitro Promoting Chondrogenic Differentiation Effect and R...mentioning

confidence: 99%

Novel 3D-printing bilayer GelMA-based hydrogel containing BP, β-TCP and exosomes for cartilage–bone integrated repair

Sun,

Feng,

et al. 2023

Biofabrication

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The integrated repair of cartilage and bone involves the migration and differentiation of cells, which has always been a difficult problem to be solved. We utilize the natural biomaterial gelatin to construct gelatin methacryloyl (GelMA), a hydrogel scaffold with high cell affinity. GelMA is mixed with different components to print a bi-layer porous hydrogel scaffold with different modulus and composition in upper and lower layers through 3D printing technology. The upper scaffold adds black phosphorus (BP) and human umbilical cord mesenchymal stem cells (hUMSCs) exosomes in GelMA, which has a relatively lower elastic modulus and is conducive to the differentiation of BMSCs into cartilage. In the lower scaffold, in addition to BP and hUMSCs exosomes, β-tricalcium phosphate (β-TCP), which has osteoconductive and osteoinductive effects, is added to GelMA. The addition of β-TCP significantly enhances the elastic modulus of the hydrogel scaffold, which is conducive to the osteogenic differentiation of BMSCs. In vitro experiments have confirmed that the bi-layer scaffolds can promote osteogenesis and chondrogenic differentiation respectively. And in the rabbit cartilage-bone injury model, MRI and micro-CT results show that the 3D printed bi-layer GelMA composite scaffold has a repair effect close to normal tissue.

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Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis: Toward a precision therapy

Cited by 6 publications

References 59 publications

Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

Mitochondrial-Oriented Injectable Hydrogel Microspheres Maintain Homeostasis of Chondrocyte Metabolism to Promote Subcellular Therapy in Osteoarthritis

Harnessing Nanomedicine for Cartilage Repair: Design Considerations and Recent Advances in Biomaterials

Novel 3D-printing bilayer GelMA-based hydrogel containing BP, β-TCP and exosomes for cartilage–bone integrated repair

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