Skip to main content

Training scientists to develop and Image materials for Tissue Engineering and Regenerative Medicine

Final Report Summary - ITERM (Training scientists to develop and Image materials for Tissue Engineering and Regenerative Medicine)

As the mean human lifespan increases, particularly in the Western world, there is a growing need for new treatment strategies for diseased, defective, or damaged tissues. It is foreseen that regenerative medicine may play an important role in this process. In regenerative medicine, tissue engineering – applying principles of engineering and life sciences-, cell transplantation and stem cells re combined. An important topic for tissue engineering will be the development of strategies to promote and monitor the integration of engineered tissue or devices such as scaffolds that carry cells or other biological factors with host tissue. To achieve this goal, the development of biomaterials and devices that can interact in a positive way with the environment and also report on its status (or surrounding environment) will be critical. In iTERM 12 ESR and one ER were recruited to develop new smart (bio)materials that could be traced after implantation. Multiple smart materials, synthetic-based as well as biomaterials were developed with intrinsic imaging capacity suited for bone and soft tissues. These materials were extensively tested in vitro and in vivo for their potential use as traceable, biocompatible materials for regenerative medicine.

Material design and matrix development: a cornerstone of Tissue Engineering
A number of imageable, naturally derived and synthetic polymers were developed. For bone-tissue engineering, bone fillers were developed in conjugation with a slow release carrier. Through the addition of specific microparticles or fluor-conjugation the mineral phase of the calcium phosphate based cements (CPC) was adapted to improve the imaging performance. To enhance the speed of bone replacement, CPC was combined with two different growth factors. Collagen sponges were modified with hemin derivates for imaging purposes.
A degradable hydrogel was developed which allowed the release of immobilized growth factors independently of the hydrogel degradation. Collagen gels were optimized for skin substitute purposes. Extracellular matrix-mimicking hydrogels were prepared based on hyaluronic acid and modified for imaging purposes. Finally, a synthetic thermosensitive polymer that closely resembles the naturally occurring extracellular matrix was optimized for cell growth and imaging. A number of novel gadolinium(III) based MR contrast agents were developed and used to coat nanoparticles. Additionally, these agents were non-covalently bound to hydrogel materials.

In vitro and in vivo evaluation
The developed materials were tested extensively in vitro (cell compatibility, imaging of phantoms, mechanical assays, etc.) and materials were combined to produce complex hybrid scaffolds with superior mechanical characteristics. Cells isolated from surgical specimens were combined with various scaffolds under predefined conditions (static and dynamic in bioreactors) to test the behaviour of the scaffolds and to test the interaction between cells and scaffolds. Developed materials were also used to attract and trap bone progenitor cells and these cells were subsequently used for bone regeneration. The experiments demonstrated that the developed materials were suited for their designed purpose: adequate cell compatibility and imageable by MR.

One of the biggest challenges in tissue engineering is follow-up of implanted scaffolds, particularly because the intrinsic characteristics of most scaffolds closely resemble native tissue. Materials were loaded with various MR imageable labels and the fate of CPC in bone defects and scaffolds for soft tissue engineering was followed. Simultaneously the image was correlated with the histological findings. Non-modified materials could hardly be distinguished from native tissues, whereas the modified materials were clearly visible. Moreover, the obtained images correlated with histological findings, i.e. the images were a clear representation of the ongoing tissue remodelling. These results showed that the designed materials could be used for non-invasive follow-up of bone and soft tissues remodelling: the fate of the grafted materials and the tissue regeneration process could be followed.

Expected final results, potential impact
iTERM expects to deliver various imageable new materials for different tissue engineering applications. New materials with great potential have been developed by iTERM ESR. It is anticipated that these new materials will significantly decrease animal use and it is likely that part of the developed materials will be further developed for clinical implementation. Usage of these materials will allow non-invasive follow-up, reduce animal usage and strengthen the economic potential of Europe. iTERM is delivering 13 highly skilled, multidisciplinary trained scientists to the field of tissue engineering and regenerative medicine, strengthening the European work force.

Contact Information
For more information, please contact the coordinator Dr. E. Oosterwijk (tel. +31-24-3614907, e-mail or visit the website: