3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels

Huang, Chun Chieh; Kang, Miya; Shirazi, Sajjad; Lu, Yu; Cooper, Lyndon F.; Gajendrareddy, Praveen; Ravindran, Sriram

doi:10.1016/j.actbio.2021.03.030

Cited by 81 publications

(81 citation statements)

References 52 publications

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“…Both engineered and naturally derived EVs encapsulated in hydrogels are promising techniques for wound healing because they deliver EVs in the wound site and ensure prolonged and sustained release [ 223 ]. The scaffolding technologies are moving towards developing so-called smart hydrogels that can sense and respond to wound environmental parameters, such as pH, ROS levels, glucose concentrations, and so on [ 224 ].…”

Section: Future Perspectivesmentioning

confidence: 99%

Extracellular Vesicles in Skin Wound Healing

et al. 2021

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Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signaling takes part in all four wound healing phases: hemostasis, inflammation, proliferation, and remodeling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration, and treatment of dermal diseases, including the stem cell-derived, plant-derived, and engineered EVs.

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Section: Future Perspectivesmentioning

confidence: 99%

Extracellular Vesicles in Skin Wound Healing

et al. 2021

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“…Bone morphogenic protein 2 (BMP2) is the only FDA-approved and most widely used growth factor in bone regeneration [93]. BMP2 treatment was reported to exert a positive immunomodulatory effect on macrophages [94] and potentiate the BMP2 signaling cascade on hBMSCs [77,95], favoring the local environment for enhanced bone regeneration. Huang et al [95] demonstrated the enhanced bone regenerative potential of BMP2-treated hBMSC EVs compared to naïve hBMSC EVs in a rat calvarial defect model in vivo.…”

Section: Pre-conditioning Parent Cells To Enhance Osteogenic Potentialmentioning

confidence: 99%

Bioactive Scaffolds Integrated with Liposomal or Extracellular Vesicles for Bone Regeneration

Kang

Lee

2021

Bioengineering

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With population aging and increased life expectancy, an increasing number of people are facing musculoskeletal health problems that necessitate therapeutic intervention at defect sites. Bone tissue engineering (BTE) has become a promising approach for bone graft substitutes as traditional treatments using autografts or allografts involve clinical complications. Significant advancements have been made in developing ideal BTE scaffolds that can integrate bioactive molecules promoting robust bone repair. Herein, we review bioactive scaffolds tuned for local bone regenerative therapy, particularly through integrating synthetic liposomal vesicles or extracellular vesicles to the scaffolds. Liposomes offer an excellent drug delivery system providing sustained release of the loaded bioactive molecules. Extracellular vesicles, with their inherent capacity to carry bioactive molecules, are emerging as an advanced substitute of synthetic nanoparticles and a novel cell-free therapy for bone regeneration. We discuss the recent advance in the use of synthetic liposomes and extracellular vesicles as bioactive materials combined with scaffolds, highlighting major challenges and opportunities for their applications in bone regeneration. We put a particular focus on strategies to integrate vesicles to various biomaterial scaffolds and introduce the latest advances in achieving sustained release of bioactive molecules from the vesicle-loaded scaffolds at the bone defect site.

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“…There also is a need to develop EVs formulations that possess extended periods of uptake into tissues. Initial studies by our group in bone regeneration using EVs tethered to hydrogels have shown the ability to produce an extended-release formulation [ 147 ]. More discussion of the means to prolong delivery of EVs appears below.…”

Section: Main Textmentioning

confidence: 99%

“…An alternate approach is genetic modification, where the EV surface is modified using a lentiviral carried plasmid for transfection of the parent cells, as we and others previously reported [ 173 – 175 ]. With the genetic modification, a stable cell line of, e.g., MSCs, can be created, from which EVs of predictable composition and properties can easily be obtained [ 147 ].…”

Section: Main Textmentioning

confidence: 99%

Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles

et al. 2021

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Background Optic neuritis (ON) is frequently encountered in multiple sclerosis, neuromyelitis optica spectrum disorder, anti-myelin oligodendrocyte glycoprotein associated disease, and other systemic autoimmune disorders. The hallmarks are an abnormal optic nerve and inflammatory demyelination; episodes of optic neuritis tend to be recurrent, and particularly for neuromyelitis optica spectrum disorder, may result in permanent vision loss. Main Body Mesenchymal stem cell (MSC) therapy is a promising approach that results in remyelination, neuroprotection of axons, and has demonstrated success in clinical studies in other neuro-degenerative diseases and in animal models of ON. However, cell transplantation has significant disadvantages and complications. Cell-free approaches utilizing extracellular vesicles (EVs) produced by MSCs exhibit anti-inflammatory and neuroprotective effects in multiple animal models of neuro-degenerative diseases and in rodent models of multiple sclerosis (MS). EVs have potential to be an effective cell-free therapy in optic neuritis because of their anti-inflammatory and remyelination stimulating properties, ability to cross the blood brain barrier, and ability to be safely administered without immunosuppression. Conclusion We review the potential application of MSC EVs as an emerging treatment strategy for optic neuritis by reviewing studies in multiple sclerosis and related disorders, and in neurodegeneration, and discuss the challenges and potential rewards of clinical translation of EVs including cell targeting, carrying of therapeutic microRNAs, and prolonging delivery for treatment of optic neuritis. Graphical Abstract

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3D Encapsulation and tethering of functionally engineered extracellular vesicles to hydrogels

Cited by 81 publications

References 52 publications

Extracellular Vesicles in Skin Wound Healing

Extracellular Vesicles in Skin Wound Healing

Bioactive Scaffolds Integrated with Liposomal or Extracellular Vesicles for Bone Regeneration

Emerging concepts in the treatment of optic neuritis: mesenchymal stem cell-derived extracellular vesicles

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