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Effect of sterilization treatment on mechanical properties, biodegradation, bioactivity and printability of GelMA hydrogels.

ABSTRACT: Gelatin methacryloyl (GelMA) hydrogel scaffolds and GelMA-based bioinks are widely used in tissue engineering and bioprinting due to their ability to support cellular functions and new tissue development. Unfortunately, while terminal sterilization of the GelMA is a critical step for translational tissue engineering applications, it can potentially cause thermal or chemical modifications of GelMA. Thus, understanding the effect of terminal sterilization on GelMA properties is an important, though often overlooked, aspect of material design for translational tissue engineering applications. To this end, we characterized the effects of FDA-approved terminal sterilization methods (autoclaving, ethylene oxide treatment, and gamma (γ)-irradiation) on GelMA prepolymer (bioink) and GelMA hydrogels in terms of the relevant properties for biomedical applications, including mechanical strength, biodegradation rate, cell culture in 2D and 3D, and printability. Autoclaving and ethylene oxide treatment of the GelMA decreased the stiffness of the hydrogel, but the treatments did not modify the biodegradation rate of the hydrogel; meanwhile, γ-irradiation increased the stiffness, reduced the pore size and significantly slowed the biodegradation rate. None of the terminal sterilization methods changed the 2D fibroblast or endothelial cell adhesion and spreading. However, ethylene oxide treatment significantly lowered the fibroblast viability in 3D cell culture. Strikingly, γ-irradiation led to significantly reduced ability of the GelMA prepolymer to undergo sol-gel transition. Furthermore, printability studies showed that the bioinks prepared from γ-irradiated GelMA had significantly reduced printability as compared to the GelMA bioinks prepared from autoclaved or ethylene oxide treated GelMA. These results reveal that the choice of the terminal sterilization method can strongly influence important properties of GelMA bioink and hydrogel. Overall, this study provides further insight into GelMA-based material design with consideration of the effect of terminal sterilization.

SUBMITTER: Rizwan M

PROVIDER: S-EPMC7733554 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The current study introduces two novel, smart polymer three-dimensional (3D)-printable interpenetrating polymer network (IPN) hydrogel biomaterials with favorable chemical, mechanical, and morphological properties for potential applications in traumatic brain injury (TBI) such as potentially assisting in the restoration of neurological function through closure of the wound deficit and neural tissue regeneration. Additionally, removal of injury matter to allow for the appropriate scaffold grafting may assist in providing a TBI treatment. Furthermore, due to the 3D printability of the IPN biomaterials, complex structures can be designed and fabricated to mimic the native shape and structure of the injury sight, which can potentially assist with neural tissue regeneration after TBI. In this study, a peptide-only approach was employed, wherein collagen and elastin in a blend with gelatin methacryloyl were prepared and crosslinked using either Irgacure or Irgacure and Genipin to form either a semi or full IPN hydrogel 3D-printable neuromimicking platform system, respectively. The scaffolds displayed favorable thermal stability and were amorphous in nature with high full width at half-maximum values. Furthermore, no alteration to the peptide secondary structure was noted using Fourier transform infrared spectroscopy. The IPN biomaterials have a stiffness of around 600 Pa and are suitable for softer tissue engineering applications-that is, the brain. Scanning electron micrographs indicated that the IPN biomaterials had a morphological structure with a significant resemblance to the native rat cortex. Both biomaterial scaffolds were shown to support the growth of PC12 cells over a 72 h period. Furthermore, the increased nuclear eccentricity and nuclear area were shown to support the postulation that the IPN biomaterials maintain the cells in a healthy state encouraging cellular mitosis and proliferation. The Genipin component of the full IPN was further shown to exhibit antimicrobial properties and this suggests that Genipin can prevent the growth of pathogens associated with postsurgical brain infections. In addition to these findings, the study presents an anomaly, wherein the full IPN is found to be more brittle than the semi IPN, a finding that is in contradiction with the literature. This research, therefore, contributes to the collection of potential biomaterials for TBI applications coupled with 3D printing and can assist in the progression of neural treatments toward patient-specific scaffolds through the development of custom scaffolds.

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Effect of sterilization treatment on mechanical properties, biodegradation, bioactivity and printability of GelMA hydrogels.

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