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.