Page 151 - Tailoring Electrospinning Techniques for Regenerative Medicine - Marc Simonet

sca olds more towards native ECM. The big challenge is to combine all di erent aspects of the ECM into one complex sca old. Additionally, each separate sca old demand can be further optimized to match and mimic native ECM.
However, it should be considered how closely the sca old should match the properties of the ECM. Certainly in regenerative medicine and related fields, being able to match the ECM in its entire spectrum would be desirable. Having methods to implement all demands into a single sca old would certainly be beneficial in order to gain a better understanding of the requirements and processes of tissue engineering. It would help to prove many hypotheses and assumptions. Improvements to match the ECM would definitely make the transition from in-vitro to in-vivo faster and diminish required in-vivo tests. One related recent example is the drug screening test developed by Organovo. For these tests, di erent cell types are bioprinted in a spatially controlled manner to replicate liver tissue.17 By matching the cells 3D environment much closer to the natural situation in the body, in-vitro drug screening tests on these cell clusters replicated the in-vivo results with higher certainty.18 However, a less holistic approach might be su icient for in-situ tissue regeneration. Relying on the regenerative potential of the body, using a sca old that is functional and supports the self-regeneration of the tissue might be good enough. The electrospun in-situ heart valve
sca olds developed within this thesis have only some similarities to ECM. The synthetic polymer fibers are much thicker than the native fibrous counterparts found in the natural valve. From this point of view, the first implanted electrospun sca olds to in-situ tissue engineer blood vessels consisted of much thinner fibers and hence were a closer match to native ECM. Unfortunately, they failed a er 1 year of implantation due to an imbalance in tissue formation vs. polymer degradation, namely because the polymer degraded faster than expected and the dense fibrous structure did not allow for su icient tissue ingrowth.19,20 Moving away from mimicking the ECM as closely as possible and using thicker 4-5 μm fibers enabled neo tissue formation in our design. The follow-up study, using a compared to PCL2kU4Un slower degrading PC(U4U) n material, showed very promising long term results regarding functionality and tissue regeneration.21
7.3.2 Mechanical compliance
In order to really duplicate the situation in the body,
the sca old requires similar mechanical properties as
its native counterpart including the ECM fibrous level.
In this way, cells will experience the same mechanical 7 state as in the native tissue. Therefore, the sca old
should have comparable mechanics as the tissue and at the same time the sca old should be built up with fibers of the same mechanical properties as e.g. type 1 collagen. The reported Young’s moduli of type 1 collagen range from a few hundred MPa to a
GENERAL DISCUSSION
149