Hydrogel-Embedded Poly(Lactic-co-Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.
Hydrogel-Embedded Poly(Lactic-co-Glycolic Acid) Microspheres for the Delivery of hMSC-Derived Exosomes to Promote Bioactive Annulus Fibrosus Repair.
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水凝胶包埋的聚（乳酸-共-乙醇酸）微球用于递送hMSC衍生的外泌体以促进生物活性纤维环修复。
DOI：
10.1177/19476035221113959
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发表时间：
2022-07
期刊：
影响因子：
2.8
通讯作者：
Iatridis, James C.
中科院分区：
文献类型：
--
作者：
DiStefano, Tyler J.;Vaso, Keti;Panebianco, Christopher J.;Danias, George;Chionuma, Henry N.;Kunnath, Kuriakose;Karoulias, Stylianos Z.;Wang, Minghui;Xu, Peng;Dave, Rajesh N.;Sahoo, Susmita;Weiser, Jennifer R.;Iatridis, James C.
Intervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell–derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system. We characterize biophysical and biochemical properties of normoxic (Nx) and hypoxic (Hx) preconditioned MSC-Exos from young, healthy donors and examine their effects on AF cell proliferation, migration, and gene expression. We then integrate a poly(lactic-co-glycolic acid) microsphere (PLGA µSphere) delivery platform within an interpenetrating network hydrogel to facilitate sustained MSC-Exo delivery. Hx MSC-Exos led to a more robust response in AF cell proliferation and migration than Nx MSC-Exos and was selected for a downstream protection experiment. Hx MSC-Exos maintained a healthy AF cell phenotype under a TNFα challenge in vitro and attenuated catabolic responses. In all functional assays, AF cell responses were more sensitive to Hx MSC-Exos than Nx MSC-Exos. PLGA µSpheres released MSC-Exos over a clinically relevant timescale without affecting hydrogel modulus or pH upon initial embedment and µSphere degradation. This MSC-Exo treatment strategy may offer benefits of stem cell therapy without the need for exogenous stem cell transplantation by stimulating cell proliferation, promoting cell migration, and protecting cells from the degenerative proinflammatory microenvironment.
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影响因子：
10.8
作者：
Anseth, KS;Metters, AT;Bowman, CN
通讯作者：
Bowman, CN
影响因子：
14
作者：
Bowles RD;Setton LA
通讯作者：
Setton LA
影响因子：
5.8
作者：
DiStefano TJ;Shmukler JO;Danias G;Iatridis JC
通讯作者：
Iatridis JC
影响因子：
3
作者：
Bibby, SRS;Jones, DA;Urban, JPG
通讯作者：
Urban, JPG
影响因子：
2.8
作者：
Bron, Johannes Leendert;Helder, Marco N.;Meisel, Hans-Jorg;Royen, Barend J. Van;Smit, Theodoor H.
通讯作者：
Smit, Theodoor H.