Page 110 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

CHAPTER 5
However, these sca olds are readily seeded with matrix producing cells, while this is not the case for more advanced in-situ tissue engineering solutions. For the in-situ approach, sca olds should be designed to mimic the mechanical behavior of native heart valves, though these may change between subjects and with age.65 Only upon recruitment and/ or bio-active stimulation of matrix synthesizing cells ECM can be formed, requiring a slow and controlled degradation of the sca old material to balance neo-tissue formation and to ensure hemodynamic functioning. Because of patient specific variations in neo-tissue formation, sca old degradation should be tightly controlled, preferably by host cells using e.g. protease-mediated degradation66 or by external stimuli for on-demand degradation.67 Due to the flexibility of the electrospinning process it would also be possible to co-electrospin a degradation trigger directly into the polymer sca old.68 This could allow, for example, an external induced stepwise degradation based on the actual rather than on the expected progress of the growing tissue. Controlled degradation might be possible by peptides build into the backbone of the polymers.69 Regulating the degradation rate of sca old materials is further important for the release of incorporated bio-active factors that direct tissue formation and may facilitate cell migration, tissue remodeling and the infiltration of blood vessels.70
One of the consequences of using slowly degrading sca old materials, however, is cellular adaptation from a synthetic to a quiescent phenotype; i.e. the cells become ‘lazy’ while sensing the presence of a supporting synthetic environment. Alternatively, the cells may attain contractile properties, resulting in sca old compaction due to traction forces,71 necessitating mechanically robust cellular micro-environments to counteract these forces.
5.6.3 Sca old fiber alignment, diameter and morphology
The fiber alignment within the sca old is important to obtain a sca old that could mimic the fibers in the ECM, such as the collagen structure in the aortic heart valve leaflet. Fibers can guide cell growth and orientation.72,73 Further, the fiber alignment in the sca old directly influences its mechanical properties and functional behavior.55 Several electrospinning techniques are available to adjust and control fiber deposition and orientation. A simple method to achieve a high degree of oriented fibers is spinning towards two parallel arranged flat electrodes.74 When expanding this method with more parallel arranged electrodes, an oriented cross or star shaped deposition can be achieved.75 A more commonly used method is changing the fiber collection speed with a rotating target.47,76 With this method a more accurate control on fiber orientation is possible,
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