Developing hyaluronic acid microgels for sustained delivery of platelet lysate for tissue engineering applications

Abstract

Platelet lysate (PL), a blood product that contains high concentrations of growth factors (GFs), can be considered as a cost-effective source of multiple GFs. In this study, hyaluronic acid (HA) based microgels were developed for delivery of PL proteins. Spherical microgel were prepared using a water in oil emulsion method. First, hyaluronic acid was grafted with tyramine groups, after which prepared microdroplets were crosslinked via an enzymatic reaction in the presence of hydrogen peroxide and horseradish peroxidase. Because of electrostatic interactions, these microgels are promising carriers for positively charged proteins entrapment like most of the GFs. When microgels are incubated in PL solution, protein loading takes place which is mainly governed by nonspecific adsorption of plasma proteins. Although this hampered loading efficiency, loading could be increased by repeated washing and incubation steps. The loaded microgels presented a sustained release of PL growth factors for a period of two weeks. When PL enriched microgels were embedded in a HA bulk hydrogel, cell proliferation was higher compared to constructs without microgels. These findings suggest that the developed microgels are a potential candidate for sustained delivery of PL growth factors and present a solution to the issue of their short half-lives in vivo.