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Barbieri Thesis - BioMedical Materials program (BMM)

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Chapter 8 – General discussion<br />

to control cell fate in vivo triggering their osteogenic differentiation into bone–<br />

synthesizing cells without adding osteogenic (growth) factors to the material itself.<br />

Then, when trying to improve mechanical properties, we increased the molecular<br />

weight of the polymer phase and the biological characteristics of the composite<br />

worsened and vice versa. Thus, we had to face with the challenge that either<br />

excessively simplifying the system, or excessively complicating it, may be detrimental<br />

for the performance efficacy of the biomaterial. This concept can be extended to a<br />

more general view: a biomaterial approach should focus on a few simple mechanisms<br />

occurring in nature that effectively influence and control cell fate and try to reproduce<br />

them in a material. In particular, in view of a simple and effective approach we should<br />

focus on simple and controllable ‘intrinsic’ properties of biomaterials that are then able<br />

to interact with the biological environment by means of protein adsorption, surface<br />

mineralization and release of certain ions that will influence on cell behaviour. For<br />

example, the surface properties or the chemistry have been reported to play important<br />

roles such biological phenomena and in instructing cells.<br />

However, as mentioned earlier, we wanted to design a biomaterial that, upon<br />

implantation, supports, or replaces, the tissue function by means of simple ‘physical’<br />

mechanisms (in view of simplifying the system). The material, once implanted, may<br />

degrade leaving room for the growing new tissue. In this scenario, the choice of<br />

material factors is crucial to trigger biological phenomena involving tissue cells and<br />

intrinsic properties of materials such as surface features or mechanical performance.<br />

For instance, successful attempts to design an artificial vocal cord were<br />

accomplished, [405] where the main issue was mimicking the viscoelastic properties of<br />

the cord since it varies its dynamic viscosity with the frequency of stimulus (i.e. the<br />

vibrational stress given by the air flush during the talk) for a proper phonation.<br />

However, this material still has to demonstrate its effectiveness in driving cell fate and<br />

supporting new cord tissue formation. This example demonstrates how challenging is<br />

to design a biomaterial that have controllable ‘multiple’ characteristics.<br />

The mechanisms of tissue formation and healing are still unknown, although new<br />

discoveries in cell biology and medicine are contributing to the development of new<br />

instructive materials that fully or partially mimic nature’s structures and regenerative<br />

mechanisms. These new insights highlight the issues of (1) what is the minimum<br />

level of material complexity required for the regeneration of specific tissues, and<br />

(2) how to balance the feasibility of new biomaterial design with the regulatory<br />

implications, costs of the final device and its ease of use by surgeons, design time<br />

and, to a less extent, available funding.<br />

As already seen, interest is growing in the exciting possibility of using simple material<br />

properties that physically or chemically influence cell behavior. Current worldwide<br />

189

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