**4. Conclusion**

neering" on Pubmed. Researchers have built models for in vitro testing and substitutes that work well within different animal models. On the other hand, there are only a few tissue engineering products that have been tested in humans and even fewer that have moved on as FDA approved product for the market. The words "tissue engineering" allowed retrieval of 46 records on clinicaltrials.gov at the end of august 2012. Beside complications regarding regulatory affairs to get a product accepted, falling in a category between medical device and pharmaceutical drugs [147, 148], some substitutes failed to show adequate mechanical properties to do the job right. Creating more physiological substitutes by recreating the ge‐ ometry of native ECM and cells is a quite interesting way to improve resistance without in‐

In this chapter, some of the existing techniques that have been published to produce tissueengineered constructs showing a customised geometry were reviewed. Most of these techni‐ ques have been developed for other applications, and adapted later for tissue engineering. Alignment of collagen fibers in collagen gel constrained uniaxially is probably the oldest one, it is a quite simple technique where cell align themselves in the axis of the constraint. This model has been combined with EMF alignment of biomolecules, a more complex tech‐ nique that direct ECM assembly in a desired orientation. Electrospun nanofibers are becom‐ ing more popular in the field and the simple modification of adding a rotating target make it an interesting technique for ECM alignment. The recent advances in microfabrication have made it easy to produce the custom culture substrates that present nanoscale structures at the ECM level. While contact or topographic guidance has been studied quite a while ago, this capability of cells to align themselves in the direction of grooves and ridges of certain dimension is interesting for tissue engineering applications, especially with cell sheet engi‐ neering. Finally, mechanical strain is a strong inducer of cell alignment that dictates the ge‐ ometry of cells in our body. This technique is of great interest for load bearing applications such as cartilage, bone or vascular tissue engineering. Each of the technique mentioned above have advantages and drawbacks, and some of them are dependent on the type of tis‐

Constrained collagen gel compaction is a simple technique that is compatible with cell seed‐ ing prior gelation, allowing for a uniform cell distribution throughout the construct. On the other hand, collagen gel presents poor mechanical properties, making them unsuitable for load bearing applications such as vascular tissue engineering. The development of hydro‐ gels has helped to partially overcome this problem [29]. Alignment of ECM and cells in EMF is an effective technique but it necessitate state-of-the-art apparatus, not commonly available in a lab, in order to generate an EMF between 4 T and 8 T. As for collagen gels, cells can be added into the solution to have a uniform cell distribution. This technique seems to be re‐ stricted at this time to biomolecules, therefore limiting its application field. It can be com‐ bined with controlled collagen gel compaction to produce a more potent alignment. Electrospinning of polymer fibers is a very interesting technique that can be applied to a lot of different kinds of polymers by simply modifying the parameters of casting. This techni‐ que is particularly effective for tubular constructs since using a cylindrical mandrel as the target will directly create the desired construct. However, it is not possible to seed cells

troducing a new material or create a thicker construct.

378 Advances in Biomaterials Science and Biomedical Applications

sue desired.

The future of tissue engineering relies on the production of more complex structures, com‐ posed of many cell types that will interact together. In order to do so, cells must be assem‐ bled together in a structure that mimics their native microenvironment. Techniques to align and organize scaffolds will continue to go forward and new technologies will arise, pushed by the constant need for tissue-engineered constructs for organ transplantation.
