Microencapsulation of Liver Spheroids with Poly(Vinyl Alcohol) Enhances Function Compared with Alginate.

Abstract

<b><i>Background and Aims:</i></b> Cell therapy approaches to treating chronic liver disease provide only transient improvements, mainly due to loss of hepatocytes after infusion. Microencapsulation in alginate has been shown to protect transplanted cells from physical stress and rejection, but the poor biocompatibility of alginate can lead to graft failure. This study aimed to evaluate a biocompatible poly(vinyl alcohol) (PVA)-based microcapsule against standard alginate for improved transplantation outcome of liver spheroids. <b><i>Materials and Methods:</i></b> Human hepatocyte spheroids were microencapsulated in alginate or PVA hydrogel microspheres. Viability and function (albumin secretion and CYP activity) of the encapsulated spheroids were assessed <i>in vitro</i> at 3, 10, and 30 days postencapsulation and compared with unencapsulated spheroids. Spheroids were implanted intraperitoneally into immunodeficient mice, and human albumin levels in serum were monitored over 30 days. Cell-free microspheres were implanted in immune-competent mice to assess material biocompatibility. <b><i>Results:</i></b> Unencapsulated spheroids aggregated extensively beyond 10 days, precluding day 30 assessment. At day 30, PVA spheroids showed significantly higher CYP1A1 induction, albumin secretion, and metabolic activity compared with alginate. Mice receiving PVA spheroids had significantly higher serum albumin after 30 days compared with alginate and unencapsulated spheroids. Empty PVA microspheres showed less evidence of foreign body response <i>in vivo</i>, whereas thicker regions of inflamed tissue were observed in the alginate group. <b><i>Conclusions:</i></b> PVA-encapsulated hepatocyte spheroids maintained better overall viability, metabolic activity, and function compared with alginate-encapsulated cells both <i>in vitro</i> and <i>in vivo</i>. Both encapsulated groups demonstrated substantially improved outcomes compared with unencapsulated cells.