Sericin improves alginate-gelatin hydrogels’ mechanical properties, porosity, durability, and viability of fibroblasts in cardiac spheroids

Abstract

Biofabrication of cardiac patches is a challenging strategy proposed as an alternative to transplantation for end-stage heart failure patients. The optimization of the bioink used for this strategy can be limited by costs, properties, and biocompatibility of its building blocks. Lately, sericin has emerged within a wide range of natural proteins, thanks to its bioadhesive and biocompatibility potential. In this study, we assessed for the first time the effects of adding silk sericin on alginate-gelatin hydrogels, proposed for cardiac applications. To this aim, we first biofabricated sericin-containing hydrogels with increasing protein concentrations. Thus, we characterized hydrogels’ mechanical behavior, porosity and structure through rheology, Brillouin microspectroscopy, and scanning electron microscopy. Then, we bioprinted the formulated hydrogels and evaluated their effects on human cardiac spheroids (CSs) in vitro. Our mechanical characterization demonstrated that adding sericin significantly enhanced the elasticity and the viscosity of alginate-gelatin hydrogels. Sericin also modified hydrogels’ swelling behavior and their pore size, increasing by 20%, 62%, and 92% in Ser1%, Ser2%, and Ser3%, respectively. Although Ser1% did not exhibit significant effects on CSs, Ser2% and Ser3% enhanced cardiac cell viability for up to 14 days compared to the sericin-free hydrogel by acting on the fibroblast population. Sericin-based bioinks showed better printability and durability with +33% and +28% intact patches after 28 days of culture at 37°C compared to alginate-gelatin. Taken together, our results validated the use of sericin as a promising component for the optimization of bioink intended for cardiac applications.

Keywords

Sericin / Hydrogels / Cardiac spheroids / Myocardial infarction / Biomaterials / Alginate / Gelatin / 3D bioprinting

Funding

Dr. Carmine Gentile was supported by a UTS Seed Funding, Heart Research Australia Grant, Perpetual IMPACT Grant, Catholic Archdiocese of Sydney Grant for Adult Stem Cell Research, and a Heart Research Institute Grant. Irina Kabakova and Hadi Mahmodi are supported by the Australian Research Council Centre of Excellence in Optical Microcombs for Breakthrough Science (CE230100006) and the Australian Research Council Centre of Excellence in Quantum Biotechnology (CE230100021). Thomas R. Cox is supported by the National Health and Medical Research Council (NHMRC). Kaitlin Wyllie is supported by the University Postgraduate Award (UPA) from the University of New South Wales (UNSW). Donatella Paolino was supported by grants from the Italian Ministry of Health (PSC SALUTE 2014–2020-POS4 “Cal-Hub-Ria”- T4-AN-09), and PNRR MAD-2022-12376814).

Conflict of interest

Carmine Gentile serves as the Guest Editor of the special issue: 3D Bioprinting DownUnder: Innovation, Advancements and Perspectives, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declare they have no competing interests.

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