FiTTeR · Developing a Fibrosis Targeting and Tissue Reparative (FiTTeR) Therapy for the Infarcted Myocardium via an Injectable Functionalized Extracellular Matrix Hydrogel
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-08-21 → 2019-08-20
- EU contribution
- €195,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Developing a Fibrosis Targeting and Tissue Reparative (FiTTeR) Therapy for the Infarcted Myocardium via an Injectable Functionalized Extracellular Matrix Hydrogel
The overall objective of the FiTTeR project was to develop characterize, and determine the efficacy of a biomaterial platform to target pathologic fibrosis and promote tissue repair. All vertebrates possess mechanisms to restore damaged tissues with outcomes ranging from regeneration to scarring. Unfortunately, the mammalian response to tissue injury most often culminates in scar formation. Accounting for nearly 45% of deaths in the developed world, fibrosisis a process that stands diametrically opposed to functional tissue repair and regeneration. Strategies to improve wound healing outcomes therefore require methods to limit fibrosis. However, no specific and localized therapies currently exist for targeting fibrosis. Poor pre-clinical and/or clinical outcomes have been reported for the inhibition of multifunctional molecules like exogenous MMP inhibitors which have failed due to detrimental off-target side effects. In the FiTTeR project, an extracellular matrix (ECM) hydrogel system was developed and validated, epithelial- and macrophage-based model systems for fibrosis were developed, and the feasibility of clinical application of ECM systems was assessed. Together, these results have provided a proof-of-concept demonstration that ECM hydrogel technologies can be used in applications to enhance tissue healing outcomes. As an MSCA fellow, I presented my research at TERMIS World Congress (Kyoto, Japan), Biologic Scaffolds Symposium (Napa Valley, USA), and TERMIS North America (Charlotte, NC). I have also co-authored publications in Advanced Materials and Advanced Drug Delivery Reviews and have a number of publications in preparation. This ambitious project was possible due to the placement within the world-renowned Stevens Group at Imperial College London. Because of the interdisciplinary nature of the research plan, this diverse research group was the ideal host for this project. I benefited greatly from working alongside experts in chemistry, materials science, cell biology, and nanoparticle technologies.
Data: CORDIS, © European Union
Project objective
As a Marie Skłodowska-Curie Fellow, I will develop, characterize, and determine the efficacy of a biomaterial platform to target pathologic fibrosis and promote tissue repair following myocardial infarction (MI). I have an ideal background and will perform well in this project based on my expertise in extracellular matrix (ECM) derived biomaterials, characterizing the immune response to biomaterials, and evaluating in vivo outcomes. The proposed system will consist of a protein fragment tethered to an injectable hydrogel. The hydrogel carrier will be composed of ECM, which has been shown to facilitate tissue repair processes by local modulation of immune cell phenotype . The cryptic protein fragment, recently isolated and recombinantly produced by the Stevens Group , has gained attention for its ability to regulate the onset of fibrosis by interfacing with cells to abrogate the release of matrix metalloproteinases (MMPs). No therapies currently exist to prevent or mitigate fibrosis. Developing a sophisticated delivery system for a cryptic protein fragment will enable the broad potential of targeting pathologic fibrosis to be realized. This system will be advantageous in simultaneously providing localized delivery, combined immunomodulatory and regulatory properties of the ECM and recombinant protein fragment, and sustained release of the protein fragment during degradation of the ECM hydrogel. The combination of my expertise (in ECM hydrogels, characterizing the host response to biomaterials, and translating technologies) and Prof Molly Stevens’s supervision and world-class interdisciplinary biomaterials-focused group, the 2014 Research Group of the Year (European Life Science Awards), at Imperial College London (ICL), together make this project ideally suited for success.
Original text from CORDIS.
Participants
- IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union