Abstract

Hydrogels are promising materials for mimicking the extra-cellular environment. Here, we present a simple methodology for the formation of a free-standing viscoelastic hydrogel from the abundant and low cost protein serum albumin. We show that the mechanical properties of the hydrogel exhibit a complicated behaviour as a function of the weight fraction of the protein component. We further use X-ray scattering to shed light on the mechanism of gelation from the formation of a fibrillary network at low weight fractions to interconnected aggregates at higher weight fractions. Given the match between our hydrogel elasticity and that of the myocardium, we investigated its potential for supporting cardiac cells in vitro. Interestingly, these hydrogels support the formation of several layers of myocytes and significantly promote the maintenance of a native-like gene expression profile compared to those cultured on glass. When confronted with a multicellular ventricular cell preparation, the hydrogels can support macroscopically contracting cardiac-like tissues with a distinct cell arrangement, and form mm-long vascular-like structures. We envisage that our simple approach for the formation of an elastic substrate from an abundant protein makes the hydrogel a compelling biomedical material candidate for a wide range of cell types.

Highlights

  • Hydrogels are promising materials for mimicking the extra-cellular environment

  • While the measurements under confined compression were possible for 1.5–9 wt% bovine SA (BSA) hydrogels, we only performed the tensile measurements of free-standing hydrogels with the Z3 wt% BSA hydrogels

  • We found that the low weight fraction hydrogels (1.5–2.5 wt% BSA) tended to collapse at B50–70% compression strain (Fig. S3, Electronic supplementary information (ESI)†), while hydrogels of higher weight fractions (Z3 wt% BSA) could sustain strains above 80%

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Summary

Introduction

Many vital cell processes, from stem cell differentiation[6] to the cell’s epigenetic landscape.[7]. CMs are highly mechanosensitive cells, and their function is altered by the underlying substrate, with cells contracting more efficiently when cultured on a matrix whose stiffness approaches that of the heart.[16] beating of these cells is inhibited on stiff substrates that mimic a diseased (stiff) cardiac extracellular matrix (ECM).[16,17] myocardium stiffness-mimicking hydrogels can generate stem cell derived engineered cardiac tissues with an improved gene/protein expression and contraction, supplying a more mature functionality and more closely resembling their adult physiological counterpart.[18,19,20,21] Here, we show that the stiffness and deformability of the engineered SA hydrogels can be modulated by changing the protein weight percentage, and we explore the potential of our platform to support CMs. Our results show that CMs attach and survive on the SA platform at similar levels to conventional stiffer substrates (glass), but importantly maintain a gene expression pattern similar to freshly isolated CMs. by plating a whole ventricular cell preparation, including muscle, vascular and stromal cells, on the BSA hydrogels can generate cardiac engineered tissues with macroscopic contraction and sustained function. We expect the method presented here to be highly accessible, and implemented in any laboratory environment, without the need for sophisticated equipment and synthetic protocols

Results and discussion
Mechanism of gelation
A Qn þ þ
BSA hydrogels as scaffolds for cardiomyocytes
Conclusion

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