Engineering tissue-specific bioactive cell delivery systems from porcine extracellular matrix hydrogels

Cell-based therapy is currently the leading approach for the development of regenerative medicine platforms. Nevertheless, transplanted cells are often susceptible to the shear forces involved in the transplantation procedure and the change of microenvironment, and therefore, exhibit poor survival rates. Furthermore, surviving cells can migrate from the injected area. Injectable cell delivery systems offer a minimally invasive administration while shielding and retaining the transplanted cells. The use of biomimetic delivery systems can also 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. The ECM is a complex mixture of structural and functional proteins, which comprises the tissue, and greatly affects the function and fate of cells. Particularly, pECM was shown to support cell culture and differentiation of multipotent and pluripotent stem cells. We have, therefore, designed pECM-based injectable systems for the delivery of various cell types.

To elaborate on the distinctive properties of pECM derived from different tissues, and their consequent ability to support cells, we decellularized and solubilized different porcine tissues and produced thermally induced pECM hydrogels. The obtained hydrogels varied in composition, structure, and mechanical properties. Consequently, the morphology and viability of mesenchymal stem cells (MSCs), as well as the spontaneous differentiation of human induced pluripotent stem cells (hiPSCs), cultured on the hydrogels, were considerably affected by the pECM origin.

We have further produced microscale carriers comprised solely of the solubilized pECM, which were mechanically stable, had a spherical shape, and a 150mm average diameter. Upon seeding MSCs, these pECM-carriers supported cell viability and proliferation along 28 days and supported hiPSCs viability and differentiation.

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