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

Area of Science:

• Biomaterials Science
• Hepatology
• Regenerative Medicine

Background:

• Cell therapy for chronic liver disease offers limited success due to rapid cell loss post-transplantation.
• Alginate microencapsulation protects cells but suffers from poor biocompatibility, leading to graft failure.
• Developing biocompatible microencapsulation materials is crucial for improving cell transplantation efficacy.

Purpose of the Study:

• To evaluate poly(vinyl alcohol) (PVA) microcapsules as a biocompatible alternative to alginate for encapsulating liver spheroids.
• To compare the viability, function, and in vivo performance of PVA-encapsulated liver spheroids against alginate-encapsulated and unencapsulated controls.

Main Methods:

• Human hepatocyte spheroids were encapsulated in alginate or PVA hydrogel microspheres.
• In vitro assessment of spheroid viability, albumin secretion, and CYP activity at 3, 10, and 30 days.
• In vivo transplantation into immunodeficient mice to monitor serum albumin levels and biocompatibility in immune-competent mice.

Main Results:

• PVA-encapsulated spheroids exhibited significantly higher CYP1A1 induction, albumin secretion, and metabolic activity at day 30 compared to alginate.
• Mice receiving PVA spheroids showed higher serum albumin levels post-transplantation than those receiving alginate or unencapsulated spheroids.
• PVA microspheres demonstrated reduced foreign body response in vivo compared to alginate, which induced significant inflammation.

Conclusions:

• PVA-based microencapsulation significantly enhances the viability, metabolic activity, and function of transplanted liver spheroids compared to alginate.
• PVA microencapsulation offers a superior biocompatible platform for liver spheroid transplantation, improving therapeutic outcomes in chronic liver disease models.
• Both alginate and PVA encapsulation improved outcomes over unencapsulated cells, but PVA demonstrated clear advantages in long-term function and biocompatibility.