Robust Fabrication of Composite 3D Scaffolds with Tissue-Specific Bioactivity: A Proof-of-Concept Study

The basic requirement of any engineered scaffold is to mimic the native tissue extracellular matrix (ECM). Despite substantial strides in understanding the ECM, scaffold fabrication processes of sufficient product robustness and bioactivity require further investigation, owing to the complexity of the natural ECM. A promising bioacive platform for cardiac tissue engineering is that of decellularized porcine cardiac ECM (pcECM, used here as a soft tissue representative model). However, this platform's complexity and batch-to-batch variability serve as processing limitations in attaining a robust and tunable cardiac tissue-specific bioactive scaffold. To address these issues, we fabricated 3D composite scaffolds (3DCSs) that demonstrate comparable physical and biochemical properties to the natural pcECM using wet electrospinning and functionalization with a pcECM hydrogel. The fabricated 3DCSs are non-immunogenic in vitro and support human mesenchymal stem cells' proliferation. Most importantly, the 3DCSs demonstrate tissue-specific bioactivity in inducing spontaneous cardiac lineage differentiation in human induced pluripotent stem cells (hiPSC) and further support the viability, functionality, and maturation of hiPSC-derived cardiomyocytes. Overall, this work illustrates the technology to fabricate robust yet tunable 3D scaffolds of tissue-specific bioactivity (with a proof of concept provided for cardiac tissues) as a platform for basic materials science studies and possible future R&D application in regenerative medicine.