Cell microencapsulation associated with islet transplantation is a rapidly expanding field. Traditional alginate microspheres still suffer from poor biocompatibility, and microencapsulation of more advanced hydrogels is challenging due to their slower gelation rates. We have developed a novel, non-cytotoxic, non-emulsion based method to produce hydrogel microspheres compatible with a wide variety of materials, called Core-Shell Spherification (CSS). Here, we demonstrate fabrication of microspheres via CSS derived from two slow-hardening hydrogels: hyaluronic acid (HA) and polyethylene glycol diacrylate (PEGDA). HA microspheres were manufactured with two different crosslinking methods: thiolation and methacrylation. Microspheres of methacrylated HA (MeHA) had the greatest swelling ratio, the largest average diameter and the lowest diffusion barrier. In contrast PEGDA microspheres had the smallest diameters, the lowest swelling ratio and the highest diffusion barrier, while microspheres of thiolated HA (ThHA) had characteristics that were in between the other two groups. To test the ability of the hydrogels to protect cells while promoting function, diabetic NOD mice received xenotransplants via intraperitoneal injections of PEGDA or MeHA microencapsulated canine islets. PEGDA microspheres reversed diabetes for the length of the study (up to 16 weeks). In contrast, islets encapsulated in MeHA microspheres at the same dose restored normoglycemia, but only transiently (3-4 weeks). Non-encapsulated canine islet transplanted at the same dose did not restore normoglycemia for any length of time.

In conclusion, CSS appears to offer several advantages to current cell encapsulation technologies, including a non-toxic microencapsulation procedure compatible with various hydrogel types.


F. Karanu: Employee; Self; LIkarda LLC. S. Harrington: Employee; Self; Likarda, LLC. L. Ott: Employee; Self; Likarda, LLC.

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