Advanced Hydrogels as Exosome Delivery Systems for Osteogenic Differentiation of MSCs: Application in Bone Regeneration

doi:10.3390/ijms22126203

Review

. 2021 Jun 8;22(12):6203.

doi: 10.3390/ijms22126203.

Advanced Hydrogels as Exosome Delivery Systems for Osteogenic Differentiation of MSCs: Application in Bone Regeneration

Elham Pishavar^{1

2}, Hongrong Luo³, Mahshid Naserifar¹, Maryam Hashemi¹, Shirin Toosi¹, Anthony Atala², Seeram Ramakrishna⁴, Javad Behravan^{1

5

6}

Affiliations

¹ Biotechnology Research Center, Pharmaceutical Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad 91735, Iran.
² Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
³ Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, China.
⁴ Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, Singapore 117581, Singapore.
⁵ School of Pharmacy, University of Waterloo, Waterloo, ON N2G 1C5, Canada.
⁶ Center for Bioengineering and Biotechnology, University of Waterloo, Waterloo, ON N2G 1C5, Canada.

PMID: 34201385
PMCID: PMC8228022
DOI: 10.3390/ijms22126203

Review

Advanced Hydrogels as Exosome Delivery Systems for Osteogenic Differentiation of MSCs: Application in Bone Regeneration

Elham Pishavar et al. Int J Mol Sci. 2021.

. 2021 Jun 8;22(12):6203.

doi: 10.3390/ijms22126203.

Authors

Elham Pishavar^{1

2}, Hongrong Luo³, Mahshid Naserifar¹, Maryam Hashemi¹, Shirin Toosi¹, Anthony Atala², Seeram Ramakrishna⁴, Javad Behravan^{1

5

6}

Affiliations

¹ Biotechnology Research Center, Pharmaceutical Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad 91735, Iran.
² Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
³ Engineering Research Center in Biomaterials, Sichuan University, Chengdu 610064, China.
⁴ Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, National University of Singapore, Singapore 117581, Singapore.
⁵ School of Pharmacy, University of Waterloo, Waterloo, ON N2G 1C5, Canada.
⁶ Center for Bioengineering and Biotechnology, University of Waterloo, Waterloo, ON N2G 1C5, Canada.

PMID: 34201385
PMCID: PMC8228022
DOI: 10.3390/ijms22126203

Abstract

Hydrogels are known as water-swollen networks formed from naturally derived or synthetic polymers. They have a high potential for medical applications and play a crucial role in tissue repair and remodeling. MSC-derived exosomes are considered to be new entities for cell-free treatment in different human diseases. Recent progress in cell-free bone tissue engineering via combining exosomes obtained from human mesenchymal stem cells (MSCs) with hydrogel scaffolds has resulted in improvement of the methodologies in bone tissue engineering. Our research has been actively focused on application of biotechnological methods for improving osteogenesis and bone healing. The following text presents a concise review of the methodologies of fabrication and preparation of hydrogels that includes the exosome loading properties of hydrogels for bone regenerative applications.

Keywords: advanced hydrogels; bone tissue engineering; exosome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
A representation of methods for 3D printing by inkjet, micro-extrusion, and laser-assisted bioprinters. (A) Inkjet printing (thermal and piezoelectric). In thermal inkjet printers, a heater creates air-pressure pulses resulting in the generation of droplets on the print. For piezoelectric inkjet printing, a mechanical pulse is generated by an actuator that forces the bio-ink droplets from the nozzle. (B) In 3D printing by micro-extrusion, three dispensing systems (pneumatic, piston-driven, and screw-driven robotics) are used to produce a continuous stream of hydrogel containing cells. (C) In laser-assisted bioprinting, laser energy induces bubble nucleation and forces droplets of bio-ink towards the substrate.

**Figure 2**
Schematic representation of exosome generation, secretion, and cargo transfer from the donor cells to the recipient cells.

**Figure 3**
Targeting miRNAs/simvastatin in mesenchymal stem cells using exosomes to enhance osteogenesis.

See this image and copyright information in PMC

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References

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1. Tonnarelli B., Centola M., Barbero A., Zeller R., Martin I. Re-engineering development to instruct tissue regeneration. Curr. Top. Dev. Biol. 2014;108:319–338. - PubMed
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1. Kasten P., Beverungen M., Lorenz H., Wieland J., Fehr M., Geiger F. Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect. Cells Tissues Organs. 2012;196:523–533. doi: 10.1159/000337490. - DOI - PubMed
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[1] Benjamin R.M. Bone health: Preventing osteoporosis. Public Health Rep. 2010;125:368–370. doi: 10.1177/003335491012500302. - DOI - PMC - PubMed

[2] Benjamin R.M. Bone health: Preventing osteoporosis. Public Health Rep. 2010;125:368–370. doi: 10.1177/003335491012500302. - DOI - PMC - PubMed

[3] Tonnarelli B., Centola M., Barbero A., Zeller R., Martin I. Re-engineering development to instruct tissue regeneration. Curr. Top. Dev. Biol. 2014;108:319–338. - PubMed

[4] Tonnarelli B., Centola M., Barbero A., Zeller R., Martin I. Re-engineering development to instruct tissue regeneration. Curr. Top. Dev. Biol. 2014;108:319–338. - PubMed

[5] Toosi S., Behravan J. Osteogenesis and bone remodeling: A focus on growth factors and bioactive peptides. Biofactors. 2020;46:326–340. doi: 10.1002/biof.1598. - DOI - PubMed

[6] Toosi S., Behravan J. Osteogenesis and bone remodeling: A focus on growth factors and bioactive peptides. Biofactors. 2020;46:326–340. doi: 10.1002/biof.1598. - DOI - PubMed

[7] Kasten P., Beverungen M., Lorenz H., Wieland J., Fehr M., Geiger F. Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect. Cells Tissues Organs. 2012;196:523–533. doi: 10.1159/000337490. - DOI - PubMed

[8] Kasten P., Beverungen M., Lorenz H., Wieland J., Fehr M., Geiger F. Comparison of platelet-rich plasma and VEGF-transfected mesenchymal stem cells on vascularization and bone formation in a critical-size bone defect. Cells Tissues Organs. 2012;196:523–533. doi: 10.1159/000337490. - DOI - PubMed

[9] Haumer A., Bourgine P.E., Occhetta P., Born G., Tasso R., Martin I. Delivery of cellular factors to regulate bone healing. Adv. Drug Deliv. Rev. 2018;129:285–294. doi: 10.1016/j.addr.2018.01.010. - DOI - PubMed

[10] Haumer A., Bourgine P.E., Occhetta P., Born G., Tasso R., Martin I. Delivery of cellular factors to regulate bone healing. Adv. Drug Deliv. Rev. 2018;129:285–294. doi: 10.1016/j.addr.2018.01.010. - DOI - PubMed

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Advanced Hydrogels as Exosome Delivery Systems for Osteogenic Differentiation of MSCs: Application in Bone Regeneration

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Advanced Hydrogels as Exosome Delivery Systems for Osteogenic Differentiation of MSCs: Application in Bone Regeneration

Authors

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Conflict of interest statement

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