Omentum ECM-based hydrogel as a platform for cardiac cell delivery

Abstract

Cardiovascular diseases remain the number one killer in Western countries. Despite recent advances and promising results in cardiac cell-based therapy, one of the remaining challenges is poor cell retention in the desired site. As a solution, cell delivery systems are developed to ensure that a sufficient number of viable cells reach the infarct area. These delivery systems are based on biomaterials that provide a surrogate microenvironment for the encapsulated cells, retaining them in the desired location post-delivery. Injectable thermoresponsive ECM-based hydrogels have been developed to achieve this goal. Unfortunately, the use of allogeneic or xenogeneic ECM may hamper the treatment due to an immune response to residual cellular content from the host. In this work, we have developed an omentum-based hydrogel capable of self-assembly under physiological conditions. Although in this study the omentum was obtained from porcine sources, it can be easily and safely extracted from the patient, serving as an autologous protective vehicle for the transported cells. We have characterized the biochemical composition, mechanical properties, and gelation and degradation kinetics of the processed biomaterial. Furthermore, the ability of the hydrogel to encapsulate cardiac cells and support their culture was evaluated. We envision that the newly developed platform may open new opportunities for personalized cell delivery to the heart and other tissues.

Modular assembly of thick multifunctional cardiac patches

“…Recently, our laboratory developed a thermoresponsive ECM-based hydrogel as a platform for cell delivery and tissue engineering (15). Here, we used the ability of the hydrogel to solidify at 37°C to serve as a biological glue for layer integration.…”

“…However, using these techniques for engineering thick 3D tissues with multicellular layers is still a challenge. On the other hand, macroporous scaffolds and hydrogels are suitable for engineering thick 3D tissues, but with these scaffolds the different tissue layers cannot be controlled separately (13)(14)(15)(16). Thus, the cells throughout the entire scaffold are exposed to the same culture conditions, topography, and biochemical content, and different tissue compartments cannot be engineered separately.…”

Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration

“…In addition, various fabrication techniques can be employed for generating cardiac patches with cellular or additional biomaterial integration. Soluble dECM has been generated from cECM, pECM, sECM, SIS, placenta, and omentum from a variety of animal sources for cardiovascular applications . Decellularization of organ tissue is followed using similar protocols as implemented for solid dECM, where detergent methods are most often used.…”

Personalized Hydrogels for Engineering Diverse Fully Autologous Tissue Implants

“…The remaining ECM material was processed using chemicals and enzymes to generate a thermoresponsive hydrogel. The human material‐based hydrogel, which was a weak hydrogel at room temperature and was composed of collagen fibers and glycosaminoglycans (Figure S1b, Supporting Information), physically cross‐linked under physiological conditions by conformational change of the digested macromolecules and their entanglement (Figure d,e; Figure S2, Supporting Information). Such hydrogels did not degrade under in vitro conditions …”