Engineering Tissue-Specific Bioactive Microenvironment from Porcine Extracellular Matrix Hydrogels

Injectable cell delivery systems for regenerative therapy offer a minimally invasive administration while shielding and retaining the transplanted cells. Furthermore, the use of biomimetic delivery systems can increase cell survival and re-acclimating in the tissue. Due to its unique bioactivity, porcine extracellular matrix (pECM) ―the natural bed of cells in the different tissues―holds a great promise as a biomaterial for cell-based therapies.

Our aim in this research was, therefore, to develop tissue-specific pECM-based injectable systems for the delivery of various cell types. ECM, isolated from different porcine tissues was enzymatically processed to produce thermally induced pECM hydrogels, which were further assessed to investigate their distinctive properties, and their consequent ability to support cells for biomedical applications. In terms of composition, each hydrogel had preserved the main collagens and GAG’s of its original tissue. Nevertheless, the collagenous profile varied between the different pECM hydrogels leading to microstructural differences in porosity and fiber size distribution. The rheological properties of the hydrogels were also evaluated, revealing soft gel behavior that varied in strength according to the pECM tissue of origin. These hydrogel characteristics highly affected their interactions with cells demonstrated through the different morphology and viability of mesenchymal stem cells (MSCs). Most importantly, the different hydrogels guided a tissue-specific spontaneous differentiation of human induced pluripotent stem cells (hiPSCs).

To conclude, pECM-based cell delivery systems benefit unique, tissue-specific attributes that affect their properties and interactions with resident cells and generate a natural supportive bed for improved cell function and in vivo transplantation outcomes.