Effects of oxygen generating scaffolds on cell survival and functional recovery following acute spinal cord injury in ra
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TISSUE ENGINEERING CONSTRUCTS AND CELL SUBSTRATES Original Research
Effects of oxygen generating scaffolds on cell survival and functional recovery following acute spinal cord injury in rats Liangle Liu1,2 Junming Wan3 Minghai Dai2 Xiuzhi Ye2 Chun Liu1 Chengxuan Tang2 Lixin Zhu ●
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Received: 18 January 2020 / Accepted: 27 October 2020 / Published online: 28 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Persistent local oxygen delivery is crucial to create a microenvironment for cell survival and nerve regeneration in acute spinal cord injury (SCI). This study aimed to fabricate calcium peroxide-based microspheres incorporated into a 3-D construct scaffold as a novel oxygen release therapy for SCI. The scaffolds were able to generate oxygen over the course of 21 days when incubated under hypoxic conditions. In vitro, GFP-labeled bone marrow-derived mesenchymal stem cells (MSCs) were planted into the scaffolds. We observed that scaffolds could enhance MSC survival under hypoxic conditions for more than 21 days. Oxygen generating scaffolds were transplanted into spinal cord injury sites of rats in vivo. Twelve weeks following transplantation, cavity areas in the injury/graft site were significantly reduced due to tissue regeneration. Additionally, the oxygen generating scaffolds improved revascularization as observed through vWF immunostaining. A striking feature was the occurrence of nerve fiber regeneration in the lesion sites, which eventually led to significant locomotion recovery. The present results indicate that the oxygen generating scaffolds have the property of sustained local oxygen release, thus facilitating regeneration in injured spinal cords. Graphical Abstract
These authors contributed equally: Liangle Liu, Junming Wan * Chengxuan Tang [email protected] * Lixin Zhu [email protected] 1
Department of Spinal Surgery, Orthopaedic Medical Center,
Zhujiang Hospital, Southern Medical University, Guangzhou 510282 Guangdong, China 2
Rui’an People’s Hospital & the third Affiliated Hospital of Wenzhou Medical University, Wenzhou 325200, China
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Tongde Hospital of Zhejiang Province, Hanzhou 310002, China
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1 Introduction Spinal cord injuries (SCI) caused by traumatic accidents are associated with high morbidity rates and have limited treatment options [1]. Following SCI, certain secondary injuries can occur, including anoxia, ischemia, and immune responses, which often lead to accumulation of myelinassociated inhibitor and glial scar formation. These worsen the serious functional impairments in those who are injured [2, 3]. Although recent studies have illustrated a limited ability of the spinal cord to recover after SCI, cavities along with peripheral dense scaring around the injury site create an inhibitory environment for neural regeneration [4]. In this regard, various synthetic materials have been used to bridge the injured site in the spinal cord in animal models [5–8]. Thus far, a
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