Biomaterials mimicking collagen-based tissues

*Bone and dermal fillers :

Work of Dr. Miléna Lama (Post-doctoral researcher):

Milena Lama, PhD

Postdoctoral project (2019-2020):  Injectable hybrid materials for tissue regeneration

Advisor: Dr. Nadine Nassif

The aim of the project is to produce organic/organic and organic/inorganic collagen-based injectable materials with suitable properties for hard and soft tissue regeneration.

A part of this project is in partnership with a global pharmaceutical leader.


PhD thesis (2016-2019): « Structure-properties relationship in dense collagen gels produced by injection of spray-dried collagen » 

Director: Dr. Nadine Nassif

Co-director: Dr. Alba Marcellan

Supervisors: Dr. Francisco M. Fernandes, Pr. Cédric Boissière

Injection of dense collagen to obtain 3D biomimetic scaffolds in terms of structure and properties is challenging for regenerative medicine since it would avoid open-surgery. Conversely it is well-known that highly concentrated collagen solutions can form tissue-like organizations [1] with required mechanical behaviours after a sol-gel transition triggered by a pH increase mimicking the so-called fibrillogenesis. Thus it is possible to obtain 3D collagen gels in vitro with suitable mechanical properties [2] and without widely used chemical crosslinkers that may lead to inflammatory responses [3]. Nevertheless, the injection of highly concentrated collagen solutions is unlikely due to their high viscosity. Recently, highly concentrated fibrillar collagen gels (18wt%) were injected – however their microstructure lacks the structural features characteristic of native tissues [4].

How to combine biomimetism and injectability of pure collagen hydrogels?

To achieve this goal we propose to concentrate acidic collagen solutions by “spray-drying”, providing dense collagen beads [5]. Then we inject these highly concentrated collagen beads into a mould mimicking a tissue defect. The fibrillogenesis in vitro is induced within the moulded collagen solutions that transform into stiff hydrogels. Electron microscopies show organizations resulting from collagen self-assembly at macroscopic length scale with different patterns depending on the collagen concentration i.e. from 3wt% to 8wt%. Mechanical tests results reveal tissue-like properties strongly linked to collagen organization highlighted at the microscale.

This study opens perspectives in tissue repair in setting the framework of a library made of biomimetic and injectable collagen hydrogels enabling minimally invasive procedures.

References

[1]       L. Besseau and M. M. Giraud-Guille, “Stabilization of fluid cholesteric phases of collagen to ordered gelated matrices.,” J. Mol. Biol., vol. 251, no. 2, pp. 197–202, 1995.

[2]       N. Nassif et al., “Self-assembled collagen-apatite matrix with bone-like hierarchy,” Chem. Mater., vol. 22, no. 11, pp. 3307–3309, 2010.

[3]       L. L. H. Huang‐Lee, D. T. Cheung, and M. E. Nimni, “Biochemical changes and cytotoxicity associated with the degradation of polymeric glutaraldehyde derived crosslinks,” J. Biomed. Mater. Res., vol. 24, no. 9, pp. 1185–1201, 1990.

[4]       N. O. Kamranpour, A. K. Miri, M. James-Bhasin, and S. N. Nazhat, “A gel aspiration-ejection system for the controlled production and delivery of injectable dense collagen scaffolds,” Biofabrication, vol. 8, no. 1, p. 0, 2016.

[5]        Patent  WO2016146954 A1

*Cornea :

Work of Dr. Chrystelle Salameh, Dr. Flore Salviat et al. « Origin of transparency in scattering biomimetic collagen materials »
https://doi.org/10.1073/pnas.2001178117