In Situ Gelling Scaffolds Loaded with Platelet Growth Factors to Improve Cardiomyocyte Survival after Ischemia

ACS Biomater Sci Eng. 2019 Jan 14;5(1):329-338. doi: 10.1021/acsbiomaterials.8b01064. Epub 2018 Dec 7.

Abstract

Myocardial infarction is caused by prolonged ischemia and it is one of the main cause that leads to heart failures. The aim of the present work was the development of in situ gelling systems, based on poloxamer 407 (P407) or sodium alginate (Alg), loaded with platelet lysate (PL) to enhance cardiomyocyte survival after ischemia. Chondroitin sulfate (CS), a negatively charged glycosaminoglycan able to interact with different positively charged bioactive molecules, such as growth factors, was also investigated with both the systems. The gelation properties of both systems (viscosity, viscoelasticity, consistency by means of penetrometry, and injectability) were characterized in a physiological environment. In vitro evaluation of biocompatibility using fetal cardiac cells (cardiomyocytes and cardiac fibroblasts) demonstrated that the PL loaded alginate/chondroitin sulfate system retained the highest number of viable cells with equal distribution of the populations of cardiomyocytes and fibroblasts. Furthermore, the ability of the systems to improve cardiomyocyte survival after ischemia was also assessed. PL allowed for the highest degree of survival of cardiomyocytes after oxidative damage (simulating ischemic conditions due to MI) and both the Alg + CS PL and, to a greater extent, the PL alone demonstrated a considerable increase in survival of cardiomyocytes. In conclusion, an in situ gelling alginate-chondroitin sulfate system, loaded with platelet lysate, was able to improve the survival of cardiomyocytes after oxidative damage resulting in a promising system to improve cardiac cell viability after ischemia.

Keywords: alginate; chondroitin sulfate; fetal cardiomyocytes and cardiac fibroblasts; in situ gelling system; platelet lysate; poloxamer.