Nanocomposite Conductive Bioinks Based on Low-Concentration GelMA and MXene Nanosheets/Gold Nanoparticles Providing Enhanced Printability of Functional Skeletal Muscle Tissues.

Selwa Boularaoui,Aya Shanti,Sarah Bawazir,Shaohong Luo,Cesare Stefanini,Nicolas Christoforou,Kamran A Khan,Sungmun Lee,Michele Lanotte

doi:10.1021/acsbiomaterials.1c01193

Abstract

There is a growing need to develop novel well-characterized biological inks (bioinks) that are customizable for three-dimensional (3D) bioprinting of specific tissue types. Gelatin methacryloyl (GelMA) is one such candidate bioink due to its biocompatibility and tunable mechanical properties. Currently, only low-concentration GelMA hydrogels (≤5% w/v) are suitable as cell-laden bioinks, allowing high cell viability, elongation, and migration. Yet, they offer poor printability. Herein, we optimize GelMA bioinks in terms of concentration and cross-linking time for improved skeletal muscle C2C12 cell spreading in 3D, and we augment these by adding gold nanoparticles (AuNPs) or a two-dimensional (2D) transition metal carbide (MXene nanosheets) for enhanced printability and biological properties. AuNP and MXene addition endowed GelMA with increased conductivity (up to 0.8 ± 0.07 and 0.9 ± 0.12 S/m, respectively, compared to 0.3 ± 0.06 S/m for pure GelMA). Furthermore, it resulted in an improvement of rheological properties and printability, specifically at 10 °C. Improvements in electrical and rheological properties led to enhanced differentiation of encapsulated myoblasts and allowed for printing highly viable (97%) stable constructs. Taken together, these results constitute a significant step toward fabrication of 3D conductive tissue constructs with physiological relevance.

Highlights

Tissue engineering is a multidisciplinary field that utilizes principles of cellular biology, mechanobiology, engineering, materials science, and medicine to develop engineered tissues that can restore, maintain, or improve damaged body tissues
We demonstrated that 2% Gelatin methacryloyl (GelMA) cross-linked for 4 min produced optimal cellular elongation and spreading
Here, we enhanced the printability and conductivity of 2% GelMA cross-linked for 4 min by incorporating it with either gold nanoparticles or MXene nanosheets

Summary

INTRODUCTION

Tissue engineering is a multidisciplinary field that utilizes principles of cellular biology, mechanobiology, engineering, materials science, and medicine to develop engineered tissues that can restore, maintain, or improve damaged body tissues. To enhance the printability and shear-thinning properties of hydrogels in general, incorporation of different additives such as nanoparticles and 2D materials has been employed and has, so far, demonstrated excellent results.[16−18] For GelMA hydrogels, in particular, efforts have been devoted to high concentrations rather than low ones, low concentrations produce better cell-laden constructs.[10]. In bioprinting, Zhu et al developed a bioink composed of gold nanorods, GelMA, and alginate, and reported enhanced functionality of printed cardiac tissue constructs.[29] efforts are still limited in terms of exploring the effect of gold nanoparticles on bioink printability and 3D bioprinted constructs properties. Two GelMA-based bioinks composed of low-concentration GelMA with spherical gold nanoparticles or with MXene nanosheets were developed, and their biological, mechanical, conductive, and rheological properties were evaluated to investigate their suitability for skeletal muscle extrusion-based bioprinting

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSIONS

Findings

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