Novel multiscale structuring techniques for 3D biomimetic scaffolds applied to bone tissue models.

New solutions are needed to rebuild diseased or damaged tissues and organs of the human body when surgical or pharmaceutical therapies do not work. The scientific fields of biomaterials and tissue engineering work towards this goal by bringing together innovations in materials science and biology to improve healing and regenerate bodily functions. When a new material or device is invented, its safety in the human body must of course be rigorously tested before it can be used. Before testing can even be considered in humans, it is necessary to test the materials first in the laboratory using cells and then if the results are good, in animals. Unfortunately, there is often little correlation between the results obtained for cells and between animals and humans. The development process can therefore be protracted and expensive, and also maybe misleading. Therefore there is a huge need to develop better laboratory models based on cells that better predict outcomes in humans, and ideally cut out animal testing all together. One of the main reasons cell based studies do not work as well as they could is that testing takes place in 2D under simulated body conditions which fail to replicate the complexity of the body, where cells live in 3D. This project seeks to design and build a laboratory based cell testing platform which better mimics the conditions of the body, taking bone as a model tissue. The ambitious approach is to use new techniques developed by the lead scientist at NTNU to structure both hard and soft materials in 3D, and in combination with different cell types, to create a synthetic structure that mimics the physical and biological aspects of bone. This structure will be designed in such a way that it can be analysed using a variety of different characterisation techniques, thereby improving our repertoire of models of the human body. To date we have built the 3D structures necessary to grow cells in and developed strategies to retrieve the samples for further analyses. Work is now focussed on expanding the complexity of the model so that more cell types can be included and a more realistic structure is achieved.

We have described how collagen fibrogenesis can be controled in alginate gels and alginate gel microbeads. We have described the effect of collagen component on bone relevant cells encapsulated in the alginate-collagen interpenatrating networks (IPN). We have furthermore showed that microbeads made from these IPN?s can be incorporated in bulk collagen gels and that selective de-gelling of the alginate can be used to release cells in a controlled manner. These results contribute to the field of biopolymer based scaffolds for bone tissue engineering.

There is currently much scientific interest in developing advanced biomaterials for tissue engineering and regenerative medicine to replace lost biological function following disease or trauma. This is a rapidly growing field of research that seeks to use combinations of implanted cells, biomaterials, and biologically active molecules to repair or regenerate damaged tissues. A significant hurdle to application of this essential research field is the necessary and extensive in vitro testing prior to in vivo animal testing before human trials can even be considered. Often there is little correlation between in vitro and in vivo results, largely because in vitro testing takes place in 2D cell cultures under simulated physiological conditions which fail to replicate the complexity of the in vivo environment. Therefore the development process can be protracted and expensive and this problem represents a significant opportunity to design an early stage in vitro testing platform which better mimics the in vivo environment. Last year the PI made a significant breakthrough which enables precise control over hydrogel gelling kinetics. This invention enables microscale structures to be made in materials that closely resemble the natural extracellular matrix. This project aims at applying this novel technique to create hierarchically structured composite scaffolds with cells. A modular design principle will be applied to control the local chemical and biological environment, facilitate the facile combining of various cell types in the same system and provide gradients of culture conditions and mechanical properties which will in turn allow easier characterisation by a variety of approaches, in an attempt to create an in vitro testing platform for bone related tissue engineering biomaterials and cancer drug development studies.