Claire HOA-REN completed her PhD at Cermav under the joint supervision of Raphaël MICHEL (CNRS Research Fellow) and Rachel AUZELY-VELTY (Professor, Université Grenoble Alpes).
Her work is entitled “Design of programmable shape-morphing hydrogels based on biocompatible polysaccharides and fibers”
Abstract:
“Hydrogels are three-dimensional networks of hydrophilic polymers that swell in aqueous media. Their structural likeness to the extracellular matrix makes them promising materials for biomedical applications. Conventional hydrogels have an isotropic structure that induces uniform swelling in aqueous environments. In contrast, shape-morphing hydrogels undergo anisotropic swelling that leads to their deformation. One strategy for designing these systems relies on the introduction of rigid microfibers within the polymer matrix. When these fibers are aligned within the macromolecular network, they act as local mechanical constraints, thereby restraining the swelling in the direction of their orientation. With this approach, it is possible to direct the swelling and control the internal stresses of the material to obtain a target shape. Such control opens the door to generating complex deformations that mimic morphologies observed in living tissues. However, a major challenge remains in translating these systems into tissue engineering: combining the use of biocompatible components with fine physicochemical control, which is essential for the robust and reproducible programming of these deformations.
In this context, the objective of this thesis is to design shape-morphing composite hydrogels with programmed deformation using biocompatible components (polysaccharide matrix and rigid microfibers).
To achieve this, hydroxyapatite (HAp) microfibers – the crystalline phase of calcium phosphate (CaP) present in bone tissue – were first synthesized to serve as deformation guides. These fibers were coated with iron oxide nanoparticles (IONPs) to give them magnetic susceptibility. The feasibility of aligning them using a magnetic field was demonstrated in a low-viscosity resin.
Subsequently, hyaluronic acid (HA) – a polysaccharide naturally abundant in the human body – was functionalized with methacrylate (MA) groups to make it photocrosslinkable. HA hydrogels were synthesized by photopolymerization and then characterized through a physicochemical study. This study enabled the identification of the conditions required to obtain a gel combining suitable mechanical properties and a swelling behavior compatible with the design of shape-morphing hydrogels. The next step was to study the magnetic alignment of the fibers in HA-MA solutions prior to their photocrosslinking. To do so, the influence of key physicochemical parameters – such as the size and magnetic susceptibility of the fibers, the viscosity of the polymer solution, and the intensity of the magnetic field – was evaluated experimentally. This systematic study led to the establishment of conditions that guarantee significant and reproducible fiber alignment. The impact of this anisotropic microstructure on the direction of the swelling was then analyzed. The results revealed a pronounced directional swelling, confirming the effect of fiber alignment on the deformation of the material. A complementary study was conducted to amplify the anisotropic nature of the swelling by optimizing the interactions between the fibers and the polymer network. This anisotropic swelling was then exploited to design shape-morphing hydrogels capable of adopting, in a programmed manner, complex and novel shapes with systems based on biocompatible components (bendings, twists, negative Gaussian curvatures). Finally, the biocompatibility of all components was confirmed. However, cell seeding tests showed poor fibroblast adhesion, requiring optimization for tissue engineering applications.”