Conformal microcapsules encapsulating microcarrier-L02 cell complexes for treatment of acetaminophen-induced liver injury in rats

Abstract

Transplantation of hepatocyte microcapsule is considered to be a promising therapy for liver injury. In view of long diffusion distances in existing cell microcapsules, transport efficiencies of nutrients, metabolic wastes, and therapeutic secretions are greatly restricted. In this study, a novel conformal microcapsule was established with L02 cells cultured on Cytodex-3 microcarriers designed as the core and alginate–chitosan–alginate (ACA) polyelectrolyte layers as the shell. When L02 cells on Cytodex-3 microcarriers grew to the late exponential phase, they were microencapsulated with thin conformal coatings by an aqueous two-phase emulsification method to ensure short and about the same distance for transport of nutrients, metabolic wastes, and therapeutic secretions between all encapsulated cells and the transplantation site. Selective permeability, mechanical stability, surface roughness and hepatic functions were characterized. It was demonstrated that conformal microcapsules enclosing microcarrier-L02 cell complexes could produce urea and human albumin continually in vitro. When the microcapsules were transplanted into rats with liver injury induced by acetaminophen, serum total bilirubin, alanine transaminase and albumin levels in vivo could be maintained normal for 60 days. Cell survival was improved and the strategy for cell microencapsulation may be promising in controlled release of therapeutic secretions for relevant diseases.