SUPMED · Supramolecular Medicine: Modular, Double Dynamic and Orthogonal Functionalization of Supramolecular Biomaterials
FP7 — People (Marie Curie Actions)
- Duration
- 2009-03-01 → 2011-02-28
- EU contribution
- €168,291
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
Supramolecular Medicine: Modular, Double Dynamic and Orthogonal Functionalization of Supramolecular Biomaterials
Project context and objectives The development of novel biomaterials with biomedical functions (such as regenerative medicine and drug delivery) is one potential approach to deliver affordable healthcare solutions in the future. Tissue engineering is an important aspect of regenerative medicine, based upon a revolutionary strategy to cultivate the patients own cells on a polymer scaffold, thereby generating new tissues and organs, which can subsequently be transplanted into their bodies. Polymers can also be used as delivery systems for the controlled delivery and release of bioactive molecules such as pharmaceuticals or vaccines to the desired tissue. Supramolecular UPyridine (UPy)-urea modified polyethylene glycols (PEGs) as supramolecular hydrogelators offer the advantage that, unlike covalently cross-linked hydrogels, the reversible nature of the hydrogen bonds exhibit much better degradability, self-healing properties and adaptability under physiological conditions. However, the low stability of the hydrogels and lack of bioactivity hinder their application. Previously in the Meijer group (UK), we have found that the stability of the UPy-urea-PEG hydrogels can be improved by increasing the length of the hydrophobic spacer between urea groups and hydrophilic PEG segments (from C6 to C8 to C10 and to C12). However, the hydrogels were only stable for one hour under physiological conditions. On the other hand, chain extension by reaction of 5-modified UPy and telechelic PEGs provided a polymer with extremely good stability, although the biodegradability was reduced significantly due to the high molecular weight of the chain-extended polymers. The aim of this research is to synthesise a 5-hydrazide modified UPy-urea-PEG hydrogelator in order to attach bioactive functionalities, such as peptides and proteins, via hydrazone formation. The second aspect of this work involves the design and synthesis of double-dynamic chain-extended polymers. These polymers are characterised by dynamic covalent connections in the main chain and supramolecular non-covalent hydrogen bonding in the side chain. They are expected to exhibit similar properties of the previous chain-extended polymers, whilst exhibiting better biodegradability due to the reversible nature of the dynamic covalent bonds in the main chain.
Data: CORDIS, © European Union
Project objective
The main objective of this project is to create a new generation of smart biomaterials with great potential for tissue engineering and controlled drug delivery. Supramolecular polymers based on quadruple hydrogen bonding ureido-pyrimidinone (UPy) moieties (developed by the host group of Prof. Dr. E. W. Meijer in Eindhoven University of Technology, the Netherlands) will be employed as a basic scaffold. To fulfill the biomaterials trinity, namely tuneable mechanical properties, biodegradability and bioactivity, we propose a unique approach to functionalize the biomaterial scaffold in order to generate biomedical activity. The combination of dynamic covalent chemistry (developed by the group of Prof. Dr. Jean-Marie Lehn in Louis Pasteur University, France where the applicant comes from) and non-covalent UPy-UPy hydrogen bonding allows for a modular (self-assembly) and orthogonal (self-sorting) approach to control cellular behaviour and activity both in vitro and in vivo. Due to their dynamic characters on both non-covalent and reversible covalent levels, they can be considered as constitutional double dynamic biomaterials, capable of response to different external stimuli (pH, temperature etc.), thus behaving as adaptive biomaterials. The results that will emerge from the current proposal are of particular interest for the fields of regenerative medicine and controlled drug delivery, which have a remarkable impact in human health care. This project will initiate the first cooperation between the host group and the group the applicant comes from, to tackle a major challenge for chemical biologists. Hence, it will contribute to European research and transfer of knowledge.
Original text from CORDIS.
Participants
- TECHNISCHE UNIVERSITEIT EINDHOVEN · EindhovenCoordinatorNetherlands
Links
Data: CORDIS, © European Union