RAPID INTRAOPERATIVE GENETIC AUGMENTATION OF AUTOGRAFTS FOR RECONSTRUCTIVE SURGERY OF SEVERE TRAUMA

Dixon, James; Thi Mai, Trang; McLaren, Jane; Ollivere, Benjamin; Scammell, Brigitte; Eltaher, Hoda

Abstract

Survivors with severe tissue injury have unmet clinical needs for better bone and soft tissue regeneration. Specifically they have progressive tissue loss due to inflammation, necrosis, infection and the development of critical size bone defects is a surgical challenge. The Reamer/Irrigator/Aspirator (RIA) system is used to recover patient bone (and stem cells) for autografting in severe trauma & infections. Addition of growth‐factors (GFs) can be transformative is such systems; however, their short‐term activity requires expensive high doses with significant side effects. We have developed a simple system to express any therapeutic gene in cells and tissues, including GF genes. Our GET technology acts ‘transiently’ meaning therapeutic proteins such as GFs are produced directly by the ‘transfected’ tissue over a short therapeutic period. We have previously shown that GF gene therapy (BMP2/VEGF) in rat calvarial defects can enhance bone repair both safely and cheaply (Raftery et al. 2019). Here we have exploited the reserve of stem cells in bone marrow (BM) and grafts, and the GET system to augment stem cell activity by rapid genetic augmentation of BMP2 and VEGF genes with the aim to re‐administer them to augment reconstructive surgery. We demonstrate the efficacy of the gene delivery approach and the enhancement of ex vivo osteogenesis by graft‐expressed BMP2 and VEGF augmentation. By delivering genes that cause the resident cells at the defect site to produce regulated levels of GFs could be the transformative approach needed to allow safe and effective bone regeneration for treating many diseases or injuries.

Citation

Dixon, J., Thi Mai, T., McLaren, J., Ollivere, B., Scammell, B., & Eltaher, H. RAPID INTRAOPERATIVE GENETIC AUGMENTATION OF AUTOGRAFTS FOR RECONSTRUCTIVE SURGERY OF SEVERE TRAUMA

• Presentation Conference Type: Conference Abstract
• Acceptance Date: Apr 1, 2022
• Online Publication Date: Apr 4, 2022
• Publication Date: 2022
• Deposit Date: Apr 26, 2023
• Journal: TISSUE ENGINEERING PART A
• Print ISSN: 1937-3341
• Electronic ISSN: 1937-335X
• Publisher: Mary Ann Liebert
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: S1
• Public URL: https://nottingham-repository.worktribe.com/output/19294336
• Publisher URL: https://www.liebertpub.com/doi/10.1089/ten.tea.2022.29025.abstracts