Hyaluronic acid microparticles for effective spheroid culture and transplantation in liver tissue

[Display omitted] •Hyaluronic acid (HA) microparticle has a microporous structure after swelling.•HA microparticles facilitate the supply of nutrients to the inside of the spheroid.•HA microparticles promote cell migration and survival in the spheroid.•Spheroid containing HA microparticles could be used for tissue regeneration. Three-dimensional (3D) cell culture is a promising method for maintaining mature cell functions due to its advantageous structural characteristics. Spheroid culture is one of the most commonly used 3D cell culture methods due to its convenience of manufacture. Successful application of spheroids requires that cells survive within the structure and engraft at transplantation sites. This study proposes a new spheroid formation method containing hyaluronic acid (HA) microparticles for 3D cell culture. The spheroids containing HA microparticles showed higher cell migration activity and a higher survival rate and albumin secretion ability after transplantation into the liver of mice, compared to plain spheroids. This 3D cell culture system with HA microparticles in spheroids could be a promising strategy to improve the engraftment and efficiency of cell therapy for regenerative medicine.