Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon-To-Bone Healing.

Song, W; Ma, Z; Wang, X; Wang, Y; Wu, D; Wang, C; He, D; Kong, L; Yu, W; Li, JJ; Li, H; He, Y

Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon-To-Bone Healing.

Song, W Ma, Z Wang, X Wang, Y Wu, D Wang, C He, D Kong, L Yu, W Li, JJ Li, H He, Y

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Adv Sci (Weinh), 2023, 10, (34), pp. e2304090
Issue Date:: 2023-12

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Field	Value	Language
dc.contributor.author	Song, W
dc.contributor.author	Ma, Z
dc.contributor.author	Wang, X
dc.contributor.author	Wang, Y
dc.contributor.author	Wu, D
dc.contributor.author	Wang, C
dc.contributor.author	He, D
dc.contributor.author	Kong, L
dc.contributor.author	Yu, W
dc.contributor.author	Li, JJ
dc.contributor.author	Li, H
dc.contributor.author	He, Y
dc.date.accessioned	2024-03-20T23:08:17Z
dc.date.available	2024-03-20T23:08:17Z
dc.date.issued	2023-12
dc.identifier.citation	Adv Sci (Weinh), 2023, 10, (34), pp. e2304090
dc.identifier.issn	2198-3844
dc.identifier.issn	2198-3844
dc.identifier.uri	http://hdl.handle.net/10453/176957
dc.description.abstract	Osteoporotic tendon-to-bone healing (TBH) after rotator cuff repair (RCR) is a significant orthopedic challenge. Considering the aligned architecture of the tendon, inflammatory microenvironment at the injury site, and the need for endogenous cell/tissue infiltration, there is an imminent need for an ideal scaffold to promote TBH that has aligned architecture, ability to modulate inflammation, and macroporous structure. Herein, a novel macroporous hydrogel comprising sodium alginate/hyaluronic acid/small extracellular vesicles from adipose-derived stem cells (sEVs) (MHA-sEVs) with aligned architecture and immunomodulatory ability is fabricated. When implanted subcutaneously, MHA-sEVs significantly improve cell infiltration and tissue integration through its macroporous structure. When applied to the osteoporotic RCR model, MHA-sEVs promote TBH by improving tendon repair through macroporous aligned architecture while enhancing bone regeneration by modulating inflammation. Notably, the biomechanical strength of MHA-sEVs is approximately two times higher than the control group, indicating great potential in reducing postoperative retear rates. Further cell-hydrogel interaction studies reveal that the alignment of microfiber gels in MHA-sEVs induces tenogenic differentiation of tendon-derived stem cells, while sEVs improve mitochondrial dysfunction in M1 macrophages (Mφ) and inhibit Mφ polarization toward M1 via nuclear factor-kappaB (NF-κb) signaling pathway. Taken together, MHA-sEVs provide a promising strategy for future clinical application in promoting osteoporotic TBH.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation.ispartof	Adv Sci (Weinh)
dc.relation.isbasedon	10.1002/advs.202304090
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Rats
dc.subject.mesh	Animals
dc.subject.mesh	Hydrogels
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Tendons
dc.subject.mesh	Extracellular Vesicles
dc.subject.mesh	Inflammation
dc.subject.mesh	Tendons
dc.subject.mesh	Animals
dc.subject.mesh	Rats
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Inflammation
dc.subject.mesh	Hydrogels
dc.subject.mesh	Extracellular Vesicles
dc.subject.mesh	Rats
dc.subject.mesh	Animals
dc.subject.mesh	Hydrogels
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Tendons
dc.subject.mesh	Extracellular Vesicles
dc.subject.mesh	Inflammation
dc.title	Macroporous Granular Hydrogels Functionalized with Aligned Architecture and Small Extracellular Vesicles Stimulate Osteoporotic Tendon-To-Bone Healing.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	Germany
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	open_access	*
dc.date.updated	2024-03-20T23:08:08Z
pubs.issue	34
pubs.publication-status	Published
pubs.volume	10
utslib.citation.issue	34

Abstract:

Osteoporotic tendon-to-bone healing (TBH) after rotator cuff repair (RCR) is a significant orthopedic challenge. Considering the aligned architecture of the tendon, inflammatory microenvironment at the injury site, and the need for endogenous cell/tissue infiltration, there is an imminent need for an ideal scaffold to promote TBH that has aligned architecture, ability to modulate inflammation, and macroporous structure. Herein, a novel macroporous hydrogel comprising sodium alginate/hyaluronic acid/small extracellular vesicles from adipose-derived stem cells (sEVs) (MHA-sEVs) with aligned architecture and immunomodulatory ability is fabricated. When implanted subcutaneously, MHA-sEVs significantly improve cell infiltration and tissue integration through its macroporous structure. When applied to the osteoporotic RCR model, MHA-sEVs promote TBH by improving tendon repair through macroporous aligned architecture while enhancing bone regeneration by modulating inflammation. Notably, the biomechanical strength of MHA-sEVs is approximately two times higher than the control group, indicating great potential in reducing postoperative retear rates. Further cell-hydrogel interaction studies reveal that the alignment of microfiber gels in MHA-sEVs induces tenogenic differentiation of tendon-derived stem cells, while sEVs improve mitochondrial dysfunction in M1 macrophages (Mφ) and inhibit Mφ polarization toward M1 via nuclear factor-kappaB (NF-κb) signaling pathway. Taken together, MHA-sEVs provide a promising strategy for future clinical application in promoting osteoporotic TBH.

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http://hdl.handle.net/10453/176957