# Designing tough and self-healing composite hydrogels for biomedical applications.

Alice Gibiino, Laurent Orgéas, Lucie Bailly, Rachel Auzély-Velty, Raphaël Michel, Mehdi Bouzid

## ► To cite this version:

Alice Gibiino, Laurent Orgéas, Lucie Bailly, Rachel Auzély-Velty, Raphaël Michel, et al.. Designing tough and self-healing composite hydrogels for biomedical applications.. Tec 21 Winter school on "Multi scale approaches and multiphysics couplings in fluid and solid mechanics " (5th Edition), Jan 2023, Grenoble, France. hal-04922108

HAL Id: hal-04922108

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Submitted on 30 Jan 2025

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# Designing tough and self-healing composite hydrogels for biomedical applications

Alice Gibiino, Laurent Orgéas, Lucie Bailly, Rachel Auzély-Velty, Raphaël Michel, Mehdi Bouzid

Univ. Grenoble Alpes, CNRS, Grenoble INP, 3SR, F-38000, Grenoble, France

Univ. Grenoble Alpes, CNRS, CERMAV, F-38000, Grenoble, France

The exceptional mechanical performance of living tissues is due to their complex and multi-composite molecular structures organized hierarchically in space. Alterations of these microstructures show a significant correlation with age and with many diseases, such as rheumatism or cancerous lesions. In this context, recent advances in biomaterials research have encouraged the design of new biomimetic materials with the ability to resist damage and to regenerate their biological functions under load. Among these materials, nanocomposite hydrogels are promising materials for applications in medicine and tissue engineering. However, controlling their self-assembly to form a self-healing system with high toughness and fatigue resistance remains a major challenge. To overcome this barrier that hinders a technological breakthrough, we aim at developing a novel composite hydrogel composed of hyaluronic acid biopolymers reinforced with inorganic silica nanoparticles (SiNPs) and interacting through dynamic covalent bonds. These strong covalent bonds have rapid assembly and disassembly kinetics, that would help the hydrogel adapt to external conditions while exhibiting high toughness. I will develop a method to functionalize and stabilize SiNPs with appropriate groups to form boronic ester bonds under physiological conditions. In addition, I will show a coarse grained molecular dynamics simulations of a model gel that will be used to investigate the microscopic mechanisms controlling the rheological response.

## Tough and self-healing hydrogel

<figure><img src="image_2.png" /></figure>

### SYNTHESIS/FUNCTIONALIZATION

<figure><img src="image_3.png" /></figure>

<figure><img src="image_4.png" /></figure>

## Experimental work

<figure><img src="image_5.png" /></figure>

### PURIFICATION

1. CENTRIFUGATION

2. DIALYSIS [acidic condition]

### PURIFICATION

1. CENTRIFUGATION

2. DIALYSIS [acidic condition]

### CHARACTERIZATION

<figure><img src="image_6.png" /></figure>

<figure><img src="image_7.png" /></figure>

## Coarse-grained model

### Langevin dynamics:

$$m \frac{d^2 \mathbf{r}_i}{d^2 t} = \mathbf{F}_i^c + \mathbf{F}_i^f + \xi(t)$$

### Truncated and shifted Lennard-Jones:

- Unit of length: $\sigma = 1$

- Unit of energy: $\epsilon = 1$

- Unit of time units in: $t^* = \sqrt{\frac{m\sigma^2}{\epsilon}}$

### Nanoparticle

<figure><img src="image_8.png" /></figure>

<figure><img src="image_9.png" /></figure>

<figure><img src="image_10.png" /></figure>

### Polymer

<figure><img src="image_11.png" /></figure>

<figure><img src="image_12.png" /></figure>

<figure><img src="image_13.png" /></figure>

<figure><img src="image_14.png" /></figure>

<figure><img src="image_15.png" /></figure>

## Conclusion and outlook

* Synthesis and characterization of SiNP-APBA.

* Study of nanoparticle dynamics and single polymer chain structure through coarse-grained Molecular Dynamic simulations.

* Formation of nanocomposite gel and analysis of the linear and non-linear mechanical response.

* Use of the Molecular Dynamic simulations to probe the microscopic dynamics of the nanocompositegel.

## References

[1] Shengchang Tang, Benjamin M Richardson, and Kristi S Anseth. Progress in Materials Science, 120:1007-738, 2021.

[2] Lavrador, P., Esteves, M. R., Gaspar, V. M., & Mano, J. F. (2021). Advanced Functional Materials, 31(8), 2005941.

[3] Stöber, W., Fink, A., & Bohn, E. Journal of colloid and interface science, 26(1), 62-69, 1968.

[4] Lee, M., Bae, K., Guillon, P., Chang, J., Arlov, Ø., Zenobi-Wong, M. ACS applied materials interfaces, 10(44), 37820-37828, 2018.

[5] P. J. Flory. Principles of polymer chemistry. Cornell university press, 1953.

[6] Valerio Sorichetti. Nanoparticle Dynamics in Polymer Solutions and Gels: A Simulation Approach. Soft Condensed Matter [cond-mat.soft]. Université de Montpellier, 2019. English. tel-02560772