Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics

Melissa J. Hernandez; Roberto Gaetani; Vera M. Pieters; Nathan W. Ng; Audrey E. Chang; Taylor R. Martin; Eva van Ingen; Emma A. Mol; Monika Dzieciatkowska; Kirk C. Hansen; Joost P.G. Sluijter; Karen L. Christman

doi:10.1002/adtp.201800032

Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics

Melissa J. Hernandez, Roberto Gaetani, Vera M. Pieters, Nathan W. Ng, Audrey E. Chang, Taylor R. Martin, Eva van Ingen, Emma A. Mol, Monika Dzieciatkowska, Kirk C. Hansen, Joost P.G. Sluijter, Karen L. Christman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

11 Citations (Scopus)

Abstract

In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications.

Original language	English
Article number	1800032
Journal	Advanced Therapeutics
Volume	1
Issue number	3
DOIs	https://doi.org/10.1002/adtp.201800032
Publication status	Published - 1 Jul 2018

Keywords

extracellular matrix
extracellular vesicles
hydrogels
microRNAs

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10.1002/adtp.201800032

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Hernandez, M. J., Gaetani, R., Pieters, V. M., Ng, N. W., Chang, A. E., Martin, T. R., van Ingen, E., Mol, E. A., Dzieciatkowska, M., Hansen, K. C., Sluijter, J. P. G., & Christman, K. L. (2018). Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics. Advanced Therapeutics, 1(3), Article 1800032. https://doi.org/10.1002/adtp.201800032

@article{46ed6d40828d48bba1bb3884dbaee42f,

title = "Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics",

abstract = "In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications. ",

keywords = "extracellular matrix, extracellular vesicles, hydrogels, microRNAs",

author = "Hernandez, {Melissa J.} and Roberto Gaetani and Pieters, {Vera M.} and Ng, {Nathan W.} and Chang, {Audrey E.} and Martin, {Taylor R.} and {van Ingen}, Eva and Mol, {Emma A.} and Monika Dzieciatkowska and Hansen, {Kirk C.} and Sluijter, {Joost P.G.} and Christman, {Karen L.}",

note = "Publisher Copyright: {\textcopyright} 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2018",

month = jul,

day = "1",

doi = "10.1002/adtp.201800032",

language = "English",

volume = "1",

journal = "Advanced Therapeutics",

publisher = "Wiley-Blackwell Publishing Ltd",

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Hernandez, MJ, Gaetani, R, Pieters, VM, Ng, NW, Chang, AE, Martin, TR, van Ingen, E, Mol, EA, Dzieciatkowska, M, Hansen, KC, Sluijter, JPG & Christman, KL 2018, 'Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics', Advanced Therapeutics, vol. 1, no. 3, 1800032. https://doi.org/10.1002/adtp.201800032

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T1 - Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics

AU - Hernandez, Melissa J.

AU - Gaetani, Roberto

AU - Pieters, Vera M.

AU - Ng, Nathan W.

AU - Chang, Audrey E.

AU - Martin, Taylor R.

AU - van Ingen, Eva

AU - Mol, Emma A.

AU - Dzieciatkowska, Monika

AU - Hansen, Kirk C.

AU - Sluijter, Joost P.G.

AU - Christman, Karen L.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications.

AB - In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications.

KW - extracellular matrix

KW - extracellular vesicles

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ER -

Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics

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