Injectable and Magnetic Responsive Hydrogels with Bioinspired Ordered Structures.

Sandra Araújo-Custódio,Manuela E Gomes,Rui L Reis,Ana R Tomás,Suzanne M Mithieux,Anthony Weiss,Bárbara B Mendes,Pedro S Babo,Manuel Gomez-Florit,Rui M A Domingues

doi:10.1021/acsbiomaterials.8b01179

Sandra Araújo-Custódio, Manuela E Gomes + Show 8 more

Open Access

https://doi.org/10.1021/acsbiomaterials.8b01179

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Abstract

Injectable hydrogels are particularly interesting for applications in minimally invasive tissue engineering and regenerative medicine strategies. However, the typical isotropic microstructure of these biomaterials limits their potential for the regeneration of ordered tissues. In the present work, we decorated rod-shaped cellulose nanocrystals with magnetic nanoparticles and coated these with polydopamine and polyethylene glycol polymer brushes to obtain chemical and colloidal stable nanoparticles. Then, these nanoparticles (0.1-0.5 wt %) were incorporated within gelatin hydrogels, creating injectable and magnetically responsive materials with potential for various biomedical applications. Nanoparticle alignment within the hydrogel matrix was achieved under exposure to uniform low magnetic fields (108 mT), resulting in biomaterials with directional microstructure and anisotropic mechanical properties. The biological performance of these nanocomposite hydrogels was studied using adipose tissue derived human stem cells. Cells encapsulated in the nanocomposite hydrogels showed high rates of viability demonstrating that the nanocomposite biomaterials are not cytotoxic. Remarkably, the microstructural patterns stemming from nanoparticle alignment induced the directional growth of seeded and, to a lower extent, encapsulated cells in the hydrogels, suggesting that this injectable system might find application in both cellular and acellular strategies targeting the regeneration of anisotropic tissues.

Highlights

In the human body, many tissues such as cartilage, skeletal muscle, corneas, muscles, blood vessels or tendons and ligaments exhibit highly anisotropic mechanical strength and hierarchically ordered composite structures
Characterization of the hybrid magnetic nanoparticles The functionality and performance of nanoparticle systems has been shown to be significantly dependent on their colloidal stability in suspension or their adequate dispersibility within polymer matrices in nanocomposites, being in general negatively affected by aggregation phenomena.[29,30,34]
In this work, we demonstrated that with low concentrations of peg-MNP decorated CNC (mCNC) (0.1-0.5 wt.%) and uniform magnetic fields with strengths as low as 108 mT, it is possible to obtain nanoparticles alignment within nanocomposite hydrogels, which result in biomaterials with anisotropic microstructure and remarkable mechanical properties

Summary

Introduction

Many tissues such as cartilage, skeletal muscle, corneas, muscles, blood vessels or tendons and ligaments exhibit highly anisotropic mechanical strength and hierarchically ordered composite structures. Cell seeding and encapsulation in 3D isotropic and anisotropic hydrogels A 10 wt.% gelatin solution was prepared in 0.1X PBS supplemented with 25 mM of sucrose in order to control osmotic pressure and improve cell viability in low ionic strength conditions during processing, as described by Carvalho A., et al.[33] To avoid bacterial growth in biological assays, the nanoparticles suspensions were ultraviolet radiation (UV) treated during 30 seconds, and dispersed by an ultrasonic processor (40 % amplitude, 60 seconds).

Results

Conclusion