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The generation of 3D tissue constructs with multiple cell types and matching mechanical properties remains a challenge in cardiac tissue engineering. Recently, 3D bioprinting has become a powerful tool to achieve these goals. Decellularized extracellular matrix (dECM) is a common scaffold material due to providing a native biochemical environment. Unfortunately, dECM’s low mechanical stability prevents usage for bioprinting applications alone. In this study, we developed bioinks composed of decellularized human heart ECM (dhECM) with either gelatin methacryloyl (GelMA) or GelMA-methacrylated hyaluronic acid (MeHA) hydrogels dual crosslinked with UV light and microbial transglutaminase (mTGase). We characterized the bioinks’ mechanical, rheological, swelling, printability, and biocompatibility properties. Composite GelMA–MeHA–dhECM (GME) hydrogels demonstrated improved mechanical properties by an order of magnitude compared to the GelMA–dhECM (GE) hydrogels. All hydrogels were extrudable and compatible with human induced pluripotent stem cell derived cardiomyocytes (iCMs) and human cardiac fibroblasts (hCFs). Tissue-like beating of the printed constructs with striated sarcomeric alpha-actinin and connexin 43 expression was observed. The order of magnitude difference between the elastic modulus of these hydrogel composites offers applications in in vitro modeling of the myocardial infarct boundary. Here, as a proof of concept, we created an infarct boundary region with control over the mechanical properties along with the cellular and macromolecular content through printing iCMs with GE bioink and hCFs with GME bioink.
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Rapid Volumetric Bioprinting of Decellularized Extracellular Matrix Bioinks
Abstract Decellularized extracellular matrix (dECM)‐based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM‐based materials. In this study, heart‐derived dECM (h‐dECM) and meniscus‐derived dECM (Ms‐dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2‐bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low‐concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte‐laden h‐dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms‐dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.
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- PAR ID:
- 10535183
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 36
- Issue:
- 34
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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