A novel engineered purified exosome product patch for tendon healing: An explant in an ex vivo model

Shi, Guidong; Wang, Yicun; Wang, Zhanwen; Thoreson, Andrew R.; Jacobson, Daniel S.; Amadio, Peter C.; Behfar, Atta; Moran, Steven L.; Zhao, Chunfeng

doi:10.1002/jor.24859

Cited by 27 publications

(52 citation statements)

References 43 publications

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“…Additionally, several studies have indicated that exosomes inhibit the expression of various pro-inflammatory mediators and cytokines, including NF-kB, IL-1β, IL-6, IL-8, IL-18, COX-2, MMP1, MMP3 MMP9, iNOS, CXCL, IFNγ, and TNFα, leading to attenuated inflammation, which is ideal for tendon regeneration [ 56 , 57 , 59 , 61 , 63 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. Zhang et al observed dramatically suppressed COX-2 factor in the TSC-Exos treatment group [ 63 ].…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

“…Liu et al also published the activation of SMAD2/3 signaling by ADSC-Exos in the promotion of tendon healing [ 57 ]. Interestingly, in a canine ex vivo model, using a purified exosome TISSEEL patch showed significantly higher amounts of tenocytes and improved biomechanical properties of the tendon, but a reduction in the expression of TGF-b [ 74 ].…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

“…Moreover, most studies observed significantly higher expression of tenogenic genes at the injury site in the exosomal treatment group, including COL-1a1, Col3a1, SCX, and tenomodulin (TNMD), suggesting that exosomes derived from various sources promote tendon repair by enhancing tenogenesis on a gene level [ 59 , 61 , 67 , 74 , 83 , 84 , 85 ].…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

“…Thankam et al found that the exosomes isolated from tenocytes and ADMSCs altered their levels of mRNA and related proteins in hypoxic environments (2% oxygen), with greater expression of matrix regenerative mediators (THSB1, NSEP1, ITIH4, and TN-C), offering a protective microenvironment for tendon healing [ 85 ]. Moreover, exosomes play a role in regulating the expression of COL-1a1, Col3a1, MMPs, and TIMPs, which is critical for creating a healthy extracellular matrix for tendon healing [ 63 , 67 , 73 , 74 , 83 , 86 ]. Hence, the exosomes promote tendon healing through balancing the remodeling of tendon ECM.…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

“…One major concern of exosomal treatment is that exosomes can only partially reach the targeted sites via passive diffusion. Common carriers used to deliver exosomes include hydrogel, fibrin glue, and gelatin methacryloyl [ 59 , 62 , 63 , 74 , 82 , 84 , 87 , 88 ]. Specifically, Liu et al reported their experience in treating Achilles tendinopathy with nitric oxide nanomotor-driving exosome-loaded microneedles (EXO/MBA-loaded MN) to improve the efficiency of exosome delivery and permeation.…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

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The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Wan

Hussain

Behfar

et al. 2022

IJMS

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Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.

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Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

See 3 more Smart Citations

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Wan

Hussain

Behfar

et al. 2022

IJMS

Self Cite

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3D Printable Hydrogel with Tunable Degradability and Mechanical Properties as a Tissue Scaffold for Pelvic Organ Prolapse Treatment

Zhu

Kwok

Haug

et al. 2023

Adv Materials Technologies

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Pelvic organ prolapse (POP) is a dysfunction that affects a large proportion of women. Current support scaffolds’ lack of biocompatibility, biodegradability, and mechanical compliance are associated with surgical complications including erosion and pain, indicating the urgent need for new tissue scaffolds with customizable functions. A new material that uses polyvinyl alcohol (PVA) as the main ingredient and is chemically tuned to possess suitable mechanical properties and degradation rates for the surgical treatment of POP is developed. Specifically, the thiol‐norbornene “click” chemistry enables the sol‐gel transition of the biomaterial under UV‐light without side‐products. Meanwhile, NaOH treatment further toughens the hydrogel with a higher crosslink density. The PVA‐based biocompatible ink can be printed with UV‐facilitated direct ink writing due to the rapidly UV‐initiated chemical crosslink; in situ image analysis and machine learning methods are applied during this procedure to quantify and improve the printing quality. The cell viability results demonstrate the biocompatibility of the POP scaffolds, suggesting the potential for future animal studies and the possibility of clinical research. This study bridges polymer chemistry and manufacturing engineering with a specific tissue engineering application to solve the common disorder of POP, shedding light on individualized medicine and intelligent systems for biomedical engineering.

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Extracellular Vesicles in Hepatobiliary Health and Disease

Parthasarathy

Hirsova

Kostallari

et al. 2023

Comprehensive Physiology

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Extracellular vesicles (EVs) are membrane-bound nanoparticles released by cells and are an important means of intercellular communication in physiological and pathological states. We provide an overview of recent advances in the understanding of EV biogenesis, cargo selection, recipient cell effects, and key considerations in isolation and characterization techniques. Studies on the physiological role of EVs have relied on cell-based model systems due to technical limitations of studying endogenous nanoparticles in vivo. Several recent studies have elucidated the mechanistic role of EVs in liver diseases, including nonalcoholic fatty liver disease, viral hepatitis, cholestatic liver disease, alcohol-associated liver disease, acute liver injury, and liver cancers. Employing disease models and human samples, the biogenesis of lipotoxic EVs downstream of endoplasmic reticulum stress and microvesicles via intracellular activation stress signaling are discussed in detail. The diverse cargoes of EVs including proteins, lipids, and nucleic acids can be enriched in a disease-specific manner. By carrying diverse cargo, EVs can directly confer pathogenic potential, for example, recruitment and activation of monocyte-derived macrophages in NASH and tumorigenicity and chemoresistance in hepatocellular carcinoma. We discuss the pathogenic role of EVs cargoes and the signaling pathways activated by EVs in recipient cells. We review the literature that EVs can serve as biomarkers in hepatobiliary diseases. Further, we describe novel approaches to engineer EVs to deliver regulatory signals to specific cell types, and thus use them as therapeutic shuttles in liver diseases. Lastly, we identify key lacunae and future directions in this promising field of discovery and development.

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A novel engineered purified exosome product patch for tendon healing: An explant in an ex vivo model

Cited by 27 publications

References 43 publications

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

3D Printable Hydrogel with Tunable Degradability and Mechanical Properties as a Tissue Scaffold for Pelvic Organ Prolapse Treatment

Extracellular Vesicles in Hepatobiliary Health and Disease

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