RegeniTherix™ - a novel theranostic technology to improve wound management

WP1 (Scaffold-Gel Development, Neotherix lead) will look at the response of wounds to the tissue scaffold and gel. Previous work examined cell interactions in vitro and performance in a porcine model over a 6-day period. We will now conduct full regulatory-standard safety tests using GMP-standard product manufactured by Neotherix as a prerequisite for clinical evaluation. In the clinic, wound samples will be collected to determine normal wound biomarker patterns and visual, biochemical and histological means will be used to determine if the introduction of the scaffold-gel combination causes any adverse response or expedites wound healing. WP1 will also study the dynamics of bioresorbable scaffold degradation in wounds. WP2 (Point-of-Care Tests – NPL lead) will develop additional fluorescence-based lateral flow (LF) immunoassays for wound biomarkers selected from the literature (eg growth factors, cytokines, proteases and their inhibitors) as well as the markers identified in the previous TSB project and markers discovered in WP3b. Working with standards, the limit of detection and dynamic range of the assays will be examined to assess their suitability for bedside/home use. Once developed, measurements on real wound samples will be conducted to validate results and determine whether faster, more convenient testing is possible with the RegeniTherix system versus a laboratory analyser. WP2 will also study the process of sampling from the thermo-reversible gel and the number/frequency of gel samples that can be taken. WP3a (Gene Expression Studies - Complement Genomics lead) will conduct gene expression studies on wound samples using microarray and Q-RT-PCR and will assess their correlation with biochemical and physical measurements generated in WP1 using multivariate data analysis (MVA) techniques. The microarray data will also be compared with existing databases and the literature to identify new candidate biomarkers that might correlate better with wound status. Q-RT-PCR tests will be developed for any new biomarkers identified. WP3b (Proteomic/Metabolite Analysis - SensaPharm lead) will use ELISA and mass spectrometry to analyse samples in support of WPs 1, 2 & 3a. It will identify suitable new protein biomarkers and source monoclonal antibodies against them for use in LF immunoassays and devices. Work will also focus on identification of small molecule biomarkers (metabolites) using Q-TOF. These data will be run together with the gene expression studies (WP3a) and will be subject to MVA. Data will be compared to parallel analyses using MALDI-TOF-MS available to UCL. WP4 (Theranostic Testing – LTHT lead) will aim to demonstrate the utility of the scaffold-gel, immunoassays and point-of-care reader and will adhere to standard operating protocols developed in previous WPs. Following characterisation of biomarkers isolated from diabetic foot ulcers undergoing standard treatment and safety testing, the scaffold-gel, will be applied to non-healing wounds and samples of gel will be collected at different times, and cooled to release the biomarkers captured. Half of the samples will be measured using the LF immunoassay and point-of-care reader, the other half will be measured using a laboratory ELISA. The aim will be to show that reproducible wound sampling for subsequent accurate bedside testing is possible. Ethical, R&D and site specific approvals will be sought by LTHT with Neotherix through the CSP system early in this project. On completion of the four WPs the results will be reviewed by the full project team and invited expert and lay advisors (Advisory Group). Benefits and any technical risks will be identified. Commercial opportunities will be identified and exploitation plans proposed, and any new IP captured and filed. This technical and commercial diligence will be used to refine the business plan and to formulate next steps.