P-250

New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation

E. Opara¹, J. McQuilling¹, J. Arenas-Herrera¹, C. Childers¹, R. Pareta¹, O. Khanna², E. Brey², H. Greisler³, A. Farney^4
1 Regenerative Medicine, Wake Forest University Health Sciences , Winston-Salem, USA; ² Pritzker Institute of Biomedical Engineering, and Department of Surgery, and Department of Cell Biology, Neurobiology and Anatomy, Illinois Institute of Technology, Chicago, USA; ³ Loyola University Medical Center, Maywood, USA; ⁴ Department of Surgery, Wake Forest University Health Sciences, Winston-Salem, USA

Objective: Severe hypoxia caused by a lack of vascular supply and an inability to retrieve encapsulated islets transplanted in the peritoneal cavity for biopsy and subsequent evaluation are obstacles to clinical application of encapsulation strategies for islet transplantation. An omentum pouch has been proposed as an alternative site of encapsulated islet transplantation, and recent studies have described a multi-layer microcapsule system suitable for co-encapsulation of islets with angiogenic protein in which the latter could be encapsulated in an external layer to induce vascularization of the encapsulated islet graft. The purpose of the present study was to determine the efficacy of FGF-1 released from the external layer of the new microcapsule system in the induction of angiogenesis.

Methods: We prepared 2 groups of alginate microspheres each measuring ~600 ?m diameter with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers. While one group of microcapsules contained no protein (control), FGF-1 (1.794 ?g/100 microcapsules) was encapsulated in the external layer of the other (test) group. From each of the 2 groups, 100 microcapsules were transplanted separately in an omentum pouch created in each normal Lewis rat, and were retrieved after 14 days for analysis of vessel density using the technique of serial sample sections stained for CD31 with quantitative 3D-Imaging.

Results: FGF-1 released from the external layer of the test microcapsules induced a mean + SD vessel density (mm²) of 198.8 + 59.2 compared to a density of 128.9 + 10.9 in pouches with control capsules (p = 0.03, n =5 animals/group).

Conclusions: The external layer of our new alginate microcapsule system is an effective drug delivery device for angiogenic protein, thus suggesting that the encapsulation system may be used for sustained islet graft function in a retrievable omentum pouch.

P-250

New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation

E. Opara¹, J. McQuilling¹, J. Arenas-Herrera¹, C. Childers¹, R. Pareta¹, O. Khanna², E. Brey², H. Greisler³, A. Farney^4
1 Regenerative Medicine, Wake Forest University Health Sciences , Winston-Salem, USA; ² Pritzker Institute of Biomedical Engineering, and Department of Surgery, and Department of Cell Biology, Neurobiology and Anatomy, Illinois Institute of Technology, Chicago, USA; ³ Loyola University Medical Center, Maywood, USA; ⁴ Department of Surgery, Wake Forest University Health Sciences, Winston-Salem, USA

Objective: Severe hypoxia caused by a lack of vascular supply and an inability to retrieve encapsulated islets transplanted in the peritoneal cavity for biopsy and subsequent evaluation are obstacles to clinical application of encapsulation strategies for islet transplantation. An omentum pouch has been proposed as an alternative site of encapsulated islet transplantation, and recent studies have described a multi-layer microcapsule system suitable for co-encapsulation of islets with angiogenic protein in which the latter could be encapsulated in an external layer to induce vascularization of the encapsulated islet graft. The purpose of the present study was to determine the efficacy of FGF-1 released from the external layer of the new microcapsule system in the induction of angiogenesis.

Methods: We prepared 2 groups of alginate microspheres each measuring ~600 ?m diameter with a semi-permeable poly-L-ornithine (PLO) membrane separating two alginate layers. While one group of microcapsules contained no protein (control), FGF-1 (1.794 ?g/100 microcapsules) was encapsulated in the external layer of the other (test) group. From each of the 2 groups, 100 microcapsules were transplanted separately in an omentum pouch created in each normal Lewis rat, and were retrieved after 14 days for analysis of vessel density using the technique of serial sample sections stained for CD31 with quantitative 3D-Imaging.

Results: FGF-1 released from the external layer of the test microcapsules induced a mean + SD vessel density (mm²) of 198.8 + 59.2 compared to a density of 128.9 + 10.9 in pouches with control capsules (p = 0.03, n =5 animals/group).

Conclusions: The external layer of our new alginate microcapsule system is an effective drug delivery device for angiogenic protein, thus suggesting that the encapsulation system may be used for sustained islet graft function in a retrievable omentum pouch.