Elaboration by electrospinning and characterization of elastomeric Scaffolds dedicated to soft tissue engineering

Soft tissues, such as connective tissues, can be submitted to very high reversible strains
and their mechanical properties are consequently characterized by a strong extensibility (isotropic or anisotropic), with a pronounced non-linear character. Unfortunately, the biodegradable synthetic materials usually used, such as the poly(lactic acid) (PLA), has a weak strain at break, a strong rigidity and a plasticity for low deformations, what makes them mechanically incompatible with biological tissues. So, a major bolt in the development of the bioabsorbable scaffolds dedicated to the reconstruction of soft tissues is due to the difficulty of conferring to these scaffolds a mechanical behavior that matches that of the tissue to be regenerated, from the early stage of the transplant.
This ambitious project focuses on the development of new biodegradable and biomimetic scaffolds having a hyperplastic behavior dedicated specifically to the reconstruction of soft tissues and to characterize their mechanical properties.
A first strategy of research consisting in using new triblock elastomers copolymers such as PLA-PEG-PLA elastomers has just begun within the framework of a project supported by the University Grenoble Alpes.
An alternate strategy in the use of synthetic polymers consists in processing directly the constitutive elements of the extracellular matrix, i.e. the collagen and the elastin. The processing of these various constituents by electrospinning and their potential use as support for cellular growth were already demonstrated. The major interest in the use of such scaffolds would be a perfect biocompatibility and potentially mechanical properties similar to those of tissues. However, these materials were individually shaped and without real control of the morphology of the Scaffold.
However, the extracellular matrix (ECM) of the connective tissue has a complex structure, composed of a double network of collagen and elastin fibers . Besides, according to the nature of the connective tissue, the structure of the ECM can be strongly anisotropic, that impacts their mechanical properties. The project of thesis is to push the bio-mimicry of the scaffolds
for connective tissues as closely as possible to the ECM by proposing the elaboration and the
mechanical characterization of new artificial ECMs.

Research strategy and expected results:
Processing and morphological characterization of Scaffolds (LRP):
nanofibers of collagen type I, V, VI and elastin will be processed by electrospinning. This innovative and very attractive process for applications in tissue engineering, allows to produce fibrous scaffolds having a morphology and the diameter of fibers compatible with the ECM of human tissues. The double network will be generated by electrospinning in parallel
collagens and elastin using 2 setups. The proportion of fibers collagen / elastin of this double network will be a key parameter of the elaboration of the artificial ECM. This double network, spontaneously constituted by an isotropic fibrous structure of random fibers, can be strongly anisotropic through the alignment of fibers collected on a rotative collector. A key point of the work will be to control the morphology of this double network in order
to make it suitable for cell growth.
Experimental characterization of the scaffold (TIMC-IMAG, Equip BioMMat): Characterizations will focus on the mechanical properties of the fibrous structures. The mechanical characterization of the double network will allow us to identify the respective influence of collagen and elastin. This characterization, coupled with the morphological observation by SEM will lead to optimize and modulate the mechanical properties of the scaffold. A wide range of mechanical properties is so expected, representing a potential interest in the reconstruction of tissue from skin to tendons.