Biocompatibility and surface structure of chemically modified immunoisolating alginate‐PLL capsules

Abstract

Grafting of encapsulated living cells has the potential to cure a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. A major factor in the biocompatibility of capsules is inadequate covering of the inflammatory poly-L-lysine (PLL) on the capsules' surface. In the present study, we investigate whether tissue responses against alginate-PLL capsules can be reduced by crosslinking the surface of the capsules with heparin or polyacrylic acid. Our transplant study in rats shows a tissue response composed of fibroblasts and macrophages on alginate-PLL-alginate and alginate-PLL-heparin capsules that was completely absent on alginate-PLL-polyacrylic acid capsules. Atomic force microscopy analyses of the capsules demonstrates that the improved biocompatibility of alginate-PLL-capsules by polyacrylic acid coating should not only be explained by a more adequate binding of PLL but also by the induction of a smoother surface. This study shows for the first time that biologic responses against capsules can be successfully deleted by chemically crosslinking biocompatible molecules on the surface of alginate-PLL capsules.

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids

“…The prevention of overgrowth was accomplished by inclusion of dexamethasone in the capsules. This is a rather different and unconventional approach since most groups, including ours [5,9,11,14,22], have focussed up to now on chemical modification of the capsules to improve the biocompatibility. However, recent new insight into the tissue responses have shown that the responses against capsules are not only initiated by the capsules chemical composition but are also caused by non-specific reactions as the consequence of surgical trauma associated with implantation of the grafts [15].…”

Alginate-based microcapsules for immunoisolation of pancreatic islets

“…Another important issue that has recently been described is the surface roughness of capsules. Bu¨nger et al [90] showed that alginate-PLL capsules provoke a strong tissue response in rats when capsules were implanted with a strong surface roughness as visualized by atomic force microscopy. This was plausibly caused by an inadequate interaction of the PLL molecules with the alginate at the surface of the capsules.…”

Improved survival of microencapsulated islets during in vitro culture and enhanced metabolic function following transplantation

“…The literature reveals, however, that success has so far been limited and non-reproducible. It is thought that the inability of encapsulated islet grafts to reproducibly achieve and maintain long-term euglycaemia is related not only to insufficient immunoprotection, but also to a variety of technical and metabolic issues, including: the encapsulation process, composition/purity of the microcapsule [12], capsule size and surface structure [13,14], poor biocompatibility [15,16], and endotoxin levels of the alginate [17,18]. Furthermore, while the addition of poly-L-lysine has been used to reduce capsule porosity [19], its addition has resulted in an increased fibrotic response [15].…”