Bioengineered extracellular vesicle-loaded bioscaffolds for therapeutic applications in regenerative medicine

Abstract

Extracellular vesicle (EV)-based technologies represent a new advancement for disease treatment. EVs can be administered systemically, injected into the injury site directly, or applied locally in conjunction with bioengineered implantable scaffolds. Matrix-bound vesicles (MBVs), a special class of vesicles localized in association with the extracellular matrix (ECM), have been identified as critical bioactive factors and shown to mediate significant regenerative functions of ECM scaffolds. Loading EVs onto bioscaffolds to mimic the MBV-ECM complex has been shown superior to EV bolus injection in recent in vivo studies, such as in providing enhanced tissue regeneration, EV retention rates, and healing efficacy. Different types of natural biomaterials, synthetic polymers, and ceramics have been developed for EV loading, and these EV functionalized biomaterials have been applied in different areas for disease treatment. The EV functionalized scaffolds can be designed to be biodegradable, off-the-shelf biomaterials as a delivery vehicle for EVs. Overall, the bioengineered EV-loaded bioscaffolds represent a promising approach for cell-free treatment in clinical applications.

Keywords

Extracellular vesicles / biomaterials / bioscaffolds / EV scaffolds / EV therapeutics / drug delivery / bioengineering

References

[1] Brennan MÁ,Mooney DJ.Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration.Adv Funct Mater2020;30:1909125 PMCID:PMC7494127

[2] Yamamoto T,Ochiya T.Latest advances in extracellular vesicles: from bench to bedside.Sci Technol Adv Mater2019;20:746-57 PMCID:PMC6691912

[3] Murphy DE,Brouwer M.Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking.Exp Mol Med2019;51:1-12 PMCID:PMC6418170

[4] Witwer KW.Extracellular vesicles versus synthetic nanoparticles for drug delivery.Nat Rev Mater2021;6:103-6

[5] Massaro C,Frattolillo V,Altucci L.Extracellular vesicle-based nucleic acid delivery: current advances and future perspectives in cancer therapeutic strategies.Pharmaceutics2020;12:980 PMCID:PMC7589909

[6] van der Merwe Y,Sakalli ET.Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function.Sci Rep2019;9:3482 PMCID:PMC6400956

[7] Huleihel L,Naranjo JD.Matrix-bound nanovesicles within ECM bioscaffolds.Sci Adv2016;2:e1600502 PMCID:PMC4928894

[8] Hao D,Ramasubramanian L.Extracellular matrix mimicking nanofibrous scaffolds modified with mesenchymal stem cell-derived extracellular vesicles for improved vascularization.Front Bioeng Biotechnol2020;8:633 PMCID:PMC7329993

[9] Alvarez-Erviti L,Yin H,Lakhal S.Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Nat Biotechnol2011;29:341-5

[10] Yan HC,Li J.The delivery of extracellular vesicles loaded in biomaterial scaffolds for bone regeneration.Front Bioeng Biotechnol2020;8:1015 PMCID:PMC7466762

[11] Litowczenko J,Staszak K,Jurga S.Milestones and current achievements in development of multifunctional bioscaffolds for medical application.Bioact Mater2021;6:2412-38 PMCID:PMC7847813

[12] Davison-Kotler E,García-Gareta E.Sources of collagen for biomaterials in skin wound healing.Bioengineering (Basel)2019;6:56 PMCID:PMC6783949

[13] Xie H,Zhang L.Extracellular vesicle-functionalized decalcified bone matrix scaffolds with enhanced pro-angiogenic and pro-bone regeneration activities.Sci Rep2017;7:45622 PMCID:PMC5377422

[14] Mardpour S,Sadeghi-Abandansari H.Hydrogel-mediated sustained systemic delivery of mesenchymal stem cell-derived extracellular vesicles improves hepatic regeneration in chronic liver failure.ACS Appl Mater Interfaces2019;11:37421-33

[15] Han C,Liang C.Human umbilical cord mesenchymal stem cell derived exosomes encapsulated in functional peptide hydrogels promote cardiac repair.Biomater Sci2019;7:2920-33

[16] Wang C,Xia K.A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury.Bioact Mater2021;6:2523-34 PMCID:PMC7873581

[17] Xiao S,Miao Y.Human acellular amniotic membrane incorporating exosomes from adipose-derived mesenchymal stem cells promotes diabetic wound healing.Stem Cell Res Ther2021;12:255 PMCID:PMC8082232

[18] Wasyłeczko M,Chwojnowski A.Review of synthetic and hybrid scaffolds in cartilage tissue engineering.Membranes (Basel)2020;10:348 PMCID:PMC7698415