Diabetic bone regeneration with nanoceria-tailored scaffolds by recapitulating cellular microenvironment: Activating integrin/TGF-β co-signaling of MSCs while relieving oxidative stress.

Autor: Singh RK; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea., Yoon DS; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea., Mandakhbayar N; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea., Li C; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea., Kurian AG; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea., Lee NH; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea., Lee JH; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address: ducious@gmail.com., Kim HW; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address: kimhw@dku.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2022 Sep; Vol. 288, pp. 121732. Date of Electronic Publication: 2022 Aug 15.
DOI: 10.1016/j.biomaterials.2022.121732
Abstrakt: Regenerating defective bone in patients with diabetes mellitus remains a significant challenge due to high blood glucose level and oxidative stress. Here we aim to tackle this issue by means of a drug- and cell-free scaffolding approach. We found the nanoceria decorated on various types of scaffolds (fibrous or 3D-printed one; named nCe-scaffold) could render a therapeutic surface that can recapitulate the microenvironment: modulating oxidative stress while offering a nanotopological cue to regenerating cells. Mesenchymal stem cells (MSCs) recognized the nanoscale (tens of nm) topology of nCe-scaffolds, presenting highly upregulated curvature-sensing membrane protein, integrin set, and adhesion-related molecules. Osteogenic differentiation and mineralization were further significantly enhanced by the nCe-scaffolds. Of note, the stimulated osteogenic potential was identified to be through integrin-mediated TGF-β co-signaling activation. Such MSC-regulatory effects were proven in vivo by the accelerated bone formation in rat calvarium defect model. The nCe-scaffolds further exhibited profound enzymatic and catalytic potential, leading to effectively scavenging reactive oxygen species in vivo. When implanted in diabetic calvarium defect, nCe-scaffolds significantly enhanced early bone regeneration. We consider the currently-exploited nCe-scaffolds can be a promising drug- and cell-free therapeutic means to treat defective tissues like bone in diabetic conditions.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE