FTY720 in immuno-regenerative and wound healing technologies for muscle, epithelial and bone regeneration

• Type of Material: Article
• Authors: Monica Behara, Georgia Institute of Technology; Steven Goudy, Emory University
• Language: English
• Date: 2023-05-12
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2023 Behara and Goudy.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fphys.2023.1148932
• Title of Journal or Parent Work: FRONTIERS IN PHYSIOLOGY
• Volume: 14
• Start Page: 1148932
• End Page: 1148932
• Grant/Funding Information: Research reported in this publication was supported by the Oral Maxillofacial Surgery Foundation (Funding ID: 2591) and the National Institute of Dental and Craniofacial Research of the National Institutes of Health under award number R01 DE028905-03.
• Keywords: SPHINGOSINE; regenerative medicine; wound healing; MULTIPLE-SCLEROSIS; immunomodulation; ANGIOGENESIS; MONOCYTES; FTY720; tissue engineering; FABRICATION; ORAL FINGOLIMOD FTY720; MOUSE; Physiology; regenerative micro-environment; Science & Technology; DELIVERY; Life Sciences & Biomedicine; SCAFFOLDS; RECRUITMENT; multiple sclerosis
• Research Categories: Engineering, Biomedical

Abstract

In 2010, the FDA approved the administration of FTY720, S1P lipid mediator, as a therapy to treat relapsing forms of multiple sclerosis. FTY720 was found to sequester pro-inflammatory lymphocytes within the lymph node, preventing them from causing injury to the central nervous system due to inflammation. Studies harnessing the anti-inflammatory properties of FTY720 as a pro-regenerative strategy in wound healing of muscle, bone and mucosal injuries are currently being performed. This in-depth review discusses the current regenerative impact of FTY720 due to its anti-inflammatory effect stratified into an assessment of wound regeneration in the muscular, skeletal, and epithelial systems. The regenerative effect of FTY720 in vivo was characterized in three animal models, with differing delivery mechanisms emerging in the last 20 years. In these studies, local delivery of FTY720 was found to increase pro-regenerative immune cell phenotypes (neutrophils, macrophages, monocytes), vascularization, cell proliferation and collagen deposition. Delivery of FTY720 to a localized wound environment demonstrated increased bone, muscle, and mucosal regeneration through changes in gene and cytokine production primarily by controlling the local immune cell phenotypes. These changes in gene and cytokine production reduced the inflammatory component of wound healing and increased the migration of pro-regenerative cells (neutrophils and macrophages) to the wound site. The application of FTY720 delivery using a biomaterial has demonstrated the ability of local delivery of FTY720 to promote local wound healing leveraging an immunomodulatory mechanism.