Sustained released of bioactive mesenchymal stromal cell‐derived extracellular vesicles from 3D‐printed gelatin methacrylate hydrogels

Born, Louis J.; McLoughlin, Shannon Theresa; Dutta, Dipankar; Mahadik, Bhushan; Jia, Xin; Fisher, John P.; Jay, Steven M.

doi:10.1002/jbm.a.37362

Cited by 41 publications

(36 citation statements)

References 36 publications

(63 reference statements)

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“…The section (perpendicular to an axis) of conical microneedle was characterized to further confirm that the GelMA-MN@3D-Exo internal contained 3D-Exo particles through the high-resolution SEM, as shown in Figure E. The release efficiency of 3D-Exo from GelMA-MN@3D-Exo in vitro is an important consideration for application . Thus, GelMA-MN hybrid with 3D-Exo labeling with PKH67 dye was immersed in phosphate buffer solution (PBS) at 37 °C to mimic the release environment in vivo .…”

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confidence: 95%

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair

et al. 2022

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Exosomes derived from mesenchymal stem cells (MSCs) have been proven to exhibit great potentials in spinal cord injury (SCI) therapy. However, conventional two-dimensional (2D) culture will inevitably lead to the loss of stemness of MSCs, which substantially limits the therapeutic potency of MSCs exosomes (2D-Exo). Exosomes derived from three-dimensional culture (3D-Exo) possess higher therapeutic efficiency which have wide applications in spinal cord therapy. Typically, conventional exosome therapy that relies on local repeated injection results in secondary injury and low efficiency. It is urgent to develop a more reliable, convenient, and effective exosome delivery method to achieve constant in situ exosomes release. Herein, we proposed a controlled 3D-exohydrogel hybrid microneedle array patch to achieve SCI repair in situ. Our studies suggested that MSCs with 3D-culturing could maintain their stemness, and consequently, 3D-Exo effectively reduced SCI-induced inflammation and glial scarring. Thus, it is a promising therapeutic strategy for the treatment of SCI.

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confidence: 95%

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair

et al. 2022

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“…Contrary to the core bioink solutions, the shell bioink printing parameters, namely the temperature and inlet pressure, were less strict to begin with. EVs were shown to keep their membrane stability even when subjected to relatively high shear stress (>1 bar) [ 65 , 66 ]. Nevertheless, the design of the delivery compartment demanded higher bio-printing resolution to allow fabrication of controlled porosity of the printed pattern, allowing proper mass transfer to the CP interior.…”

Section: Discussionmentioning

confidence: 99%

“…This finding sets the ground for an additional mechanism of sustained release of EVs from polymer-based matrices, mediated by affinity binding. Thus far, EVs sustained delivery was only attempted by encapsulation inside a scaffold or hydrogel, making matrix degradation the limiting factor for drug release rate [ 66 , 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

“…Still, the release profile from the alginate matrix was considered rapid, as more than 75% of the EVs were released within 2 days. However, other EV delivery systems also exhibited an initial burst release with similar cumulative release profiles [ 66 , 69 ]. The obtained release profile, along with the mechanical stiffness of the CP ( Figure 5 B), dictate that the optimal time point for future applications involving patch implementation will be at most 24 h after printing.…”

Section: Discussionmentioning

confidence: 99%

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Three-Dimensional Bio-Printed Cardiac Patch for Sustained Delivery of Extracellular Vesicles from the Interface

Bar

Kryukov

Cohen

2022

Gels

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Cardiac tissue engineering has emerged as a promising strategy to treat infarcted cardiac tissues by replacing the injured region with an ex vivo fabricated functional cardiac patch. Nevertheless, integration of the transplanted patch with the host tissue is still a burden, limiting its clinical application. Here, a bi-functional, 3D bio-printed cardiac patch (CP) design is proposed, composed of a cell-laden compartment at its core and an extracellular vesicle (EV)-laden compartment at its shell for better integration of the CP with the host tissue. Alginate-based bioink solutions were developed for each compartment and characterized rheologically, examined for printability and their effect on residing cells or EVs. The resulting 3D bio-printed CP was examined for its mechanical stiffness, showing an elastic modulus between 4–5 kPa at day 1 post-printing, suitable for transplantation. Affinity binding of EVs to alginate sulfate (AlgS) was validated, exhibiting dissociation constant values similar to those of EVs with heparin. The incorporation of AlgS-EVs complexes within the shell bioink sustained EV release from the CP, with 88% cumulative release compared with 92% without AlgS by day 4. AlgS also prolonged the release profile by an additional 2 days, lasting 11 days overall. This CP design comprises great potential at promoting more efficient patch assimilation with the host.

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“…It is also possible to incorporate EVs into 3D-printable bio-ink. Born et al incorporated MSC-derived EVs into GelMA hydrogel bio-ink and demonstrated that increasing the concentration of a crosslinker during gelation can improve the sustained release of the pro-angiogenic EVs [ 182 ]. Chen et al, used a bio-ink composed of MSC-derived exosomes, decellularized cartilage ECM, and GelMA hydrogel to 3D print a biocompatible scaffold which was implanted on a rabbit model with an osteochondral defect.…”

Section: Hard Porous and Fibrous Scaffoldsmentioning

confidence: 99%

Production and Utility of Extracellular Vesicles with 3D Culture Methods

Ester

Day

2023

Pharmaceutics

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In recent years, extracellular vesicles (EVs) have emerged as promising biomarkers, cell-free therapeutic agents, and drug delivery carriers. Despite their great clinical potential, poor yield and unscalable production of EVs remain significant challenges. When using 3D culture methods, such as scaffolds and bioreactors, large numbers of cells can be expanded and the cell environment can be manipulated to control the cell phenotype. This has been employed to successfully increase the production of EVs as well as to enhance their therapeutic effects. The physiological relevance of 3D cultures, such as spheroids, has also provided a strategy for understanding the role of EVs in the pathogenesis of several diseases and to evaluate their role as tools to deliver drugs. Additionally, 3D culture methods can encapsulate EVs to achieve more sustained therapeutic effects as well as prevent premature clearance of EVs to enable more localised delivery and concentrated exosome dosage. This review highlights the opportunities and drawbacks of different 3D culture methods and their use in EV research.

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Sustained released of bioactive mesenchymal stromal cell‐derived extracellular vesicles from 3D‐printed gelatin methacrylate hydrogels

Cited by 41 publications

References 36 publications

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair

Three-Dimensional-Cultured MSC-Derived Exosome-Hydrogel Hybrid Microneedle Array Patch for Spinal Cord Repair

Three-Dimensional Bio-Printed Cardiac Patch for Sustained Delivery of Extracellular Vesicles from the Interface

Production and Utility of Extracellular Vesicles with 3D Culture Methods

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