MOFs-Based Nitric Oxide Therapy for Tendon Regeneration
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ARTICLE
Cite as Nano-Micro Lett. (2021) 13:23 Received: 18 July 2020 Accepted: 29 September 2020 © The Author(s) 2020
https://doi.org/10.1007/s40820-020-00542-x
MOFs‑Based Nitric Oxide Therapy for Tendon Regeneration Jun Chen1, Dandan Sheng1, Ting Ying2, Haojun Zhao3, Jian Zhang1, Yunxia Li1, He Xu2 *, Shiyi Chen1 *
HIGHLIGHTS • A system that NO-loaded metal–organic frameworks encapsulated in PCL/Gel aligned coaxial scaffold is successfully constructed. • The system enables to release NO slowly (1.67 nM h−1) and stably in a long period (15 d) without a burst release in the initial 48 h. • The scaffold can promote the regeneration of the injured tendon with maturer collagen fibers and better mechanical properties by angiogenesis.
ABSTRACT Tendon regeneration is still a great challenge due to its
avascular structure and low self-renewal capability. The nitric oxide (NO) therapy emerges as a promising treatment for inducing the regeneration of injured tendon by angiogenesis. Here, in this study, a system that NO-loaded metal–organic frameworks (MOFs) encapsulated in polycaprolactone (PCL)/gelatin (Gel) aligned coaxial scaffolds (NMPGA) is designed and prepared for tendon repair. In this system, NO is able to
be released in vitro at a slow and stable average speed of 1.67 nM h−1 as long as 15 d without a burst release stage in the initial 48 h. Furthermore, NMPGA can not only improve the tubular formation capability of endothelial cells in vitro but also obviously increase the blood perfusion near the injured tendon in vivo, leading to accelerating the maturity of collagen and recovery of biomechanical strength of the regenerated tendon tissue. As a NO-loaded MOFs therapeutic system, NMPGA can promote tendon regeneration in a shorter healing period with better biomechanical properties in comparison with control group by angiogenesis. Therefore, this study not only provides a promising scaffold for tendon regeneration, but also paves a new way to develop a NO-based therapy for biomedical application in the future. KEYWORDS Nitric oxide; Metal–organic frameworks; Tendon; Tissue regeneration; Angiogenesis
Jun Chen, Dandan Sheng and Ting Ying contributed equally to this work * 1 2 3
He Xu, [email protected]; Shiyi Chen, [email protected] Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, People’s Republic of China College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, People’s Republic of China Department of Ultrasound, Jing’an District Center Hospital, Fudan University, Shanghai 200040, People’s Republic of China Vol.:(0123456789)
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1 Introduction Tendons are the core component of the locomotor system, where injuries will lead to partial or complete loss of motor function [1]. Annually, there are over 15 million incidents of tendon injuries worldwide, even worse to disability [2]. Due to the fact that tendons are hypovascular tissue, it is very difficult for tendon regeneration because of the disruption of blood supply after
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