Project acronym BONDS
Project Bilayered ON-Demand Scaffolds: On-Demand Delivery from induced Pluripotent Stem Cell Derived Scaffolds for Diabetic Foot Ulcers
Researcher (PI) Cathal KEARNEY
Host Institution (HI) ROYAL COLLEGE OF SURGEONS IN IRELAND
Country Ireland
Call Details Starting Grant (StG), PE8, ERC-2017-STG
Summary This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation.
Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact.
This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.
Summary
This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation.
Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact.
This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.
Max ERC Funding
1 372 135 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym REACT
Project REsponsive theranostic nanosystems for Advanced Cancer Treatment
Researcher (PI) Eduardo RUIZ-HERNANDEZ
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Starting Grant (StG), PE8, ERC-2017-STG
Summary REACT aims to dramatically impact the targeted release of diagnostic agents and drugs with nanomedicines that respond to biological cues or changing pathophysiological conditions, thus enabling ultrasensitive diagnosis and exquisite therapy selectivity. Nanomedicine research against cancer focuses on the local targeted delivery of chemotherapeutics to enhance drug efficacy and reduce side effects. Despite all the efforts in the design of chemotherapeutic agents as nanomedicines, hardly any improvement has been translated into benefits for patients’ survival. There is an urgent need for improved carrier systems able to deliver high doses of diagnostic agents and anti-cancer drugs to the tumor. Stimuli responsive carriers are promising candidates since the release of the cargo can be triggered locally in the tumor environment. Currently, there exists an unparalleled effort to identify genes, proteins and metabolites implicated in human disease and utilize systems biology and mathematical approaches in order to develop new prognostic tools for the treatment of cancer and develop more targeted therapies for patients. As an expert in drug delivery systems, the PI intends to bring all these efforts and advances into the design of stimuli responsive organic-inorganic hybrid nanoparticles that can adapt their response to the biological milieu. The novel engineered delivery systems will consist of an inorganic porous matrix surface-modified with tumor-specific molecules with the ability to sense changes in the environmental conditions and react by providing a proportional release. These nanosystems can potentially be employed for early in vitro diagnosis through effective screening of deadly tumors, such as neuroblastoma and glioblastoma. Moreover, through the sustained delivery of the nanosystems from injectable gels that can be locally implanted in patients at risk of developing a tumor, a clinically relevant tool for in vivo diagnosis and targeted therapy can be achieved.
Summary
REACT aims to dramatically impact the targeted release of diagnostic agents and drugs with nanomedicines that respond to biological cues or changing pathophysiological conditions, thus enabling ultrasensitive diagnosis and exquisite therapy selectivity. Nanomedicine research against cancer focuses on the local targeted delivery of chemotherapeutics to enhance drug efficacy and reduce side effects. Despite all the efforts in the design of chemotherapeutic agents as nanomedicines, hardly any improvement has been translated into benefits for patients’ survival. There is an urgent need for improved carrier systems able to deliver high doses of diagnostic agents and anti-cancer drugs to the tumor. Stimuli responsive carriers are promising candidates since the release of the cargo can be triggered locally in the tumor environment. Currently, there exists an unparalleled effort to identify genes, proteins and metabolites implicated in human disease and utilize systems biology and mathematical approaches in order to develop new prognostic tools for the treatment of cancer and develop more targeted therapies for patients. As an expert in drug delivery systems, the PI intends to bring all these efforts and advances into the design of stimuli responsive organic-inorganic hybrid nanoparticles that can adapt their response to the biological milieu. The novel engineered delivery systems will consist of an inorganic porous matrix surface-modified with tumor-specific molecules with the ability to sense changes in the environmental conditions and react by providing a proportional release. These nanosystems can potentially be employed for early in vitro diagnosis through effective screening of deadly tumors, such as neuroblastoma and glioblastoma. Moreover, through the sustained delivery of the nanosystems from injectable gels that can be locally implanted in patients at risk of developing a tumor, a clinically relevant tool for in vivo diagnosis and targeted therapy can be achieved.
Max ERC Funding
1 498 346 €
Duration
Start date: 2019-01-01, End date: 2023-12-31
