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B De Haan

Publications and source records attributed to B De Haan.

4 recordsLinked to original sources

Effect of the alginate composition on the biocompatibility of alginate-polylysine microcapsules.

Alginate-polylysine (PLL) capsules are commonly applied for immunoprotection of endocrine tissues. Alginate is composed of mannuronic acid (M) and guluronic acid (G). Different types of alginate have different ratios of G to M, but little is known of the influence of these differences on biocompatibility. Therefore, we have investigated in vivo the effect of the G-content of the alginate on the biocompatibility of the capsules. Capsules prepared of commercially available alginates with either a high or an intermediate G-content were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. The fibrotic reaction was more severe against high-G alginate capsules than to intermediate-G alginate capsules. The majority of the high-G capsules proved to be overgrown and adherent to the abdominal organs whereas with intermediate-G alginate most capsules were found freely floating in the peritoneal cavity and free of any adhesion of cells. This was not caused by the alginate as such but rather by inadequate binding of high-G alginate to PLL since in the absence of PLL, i.e. with beads instead of capsules, no fibrotic reaction was observed. As high-G alginates have beneficial effects for islet encapsulation, efforts should be made to apply polycations which more effectively interact with high-G alginate than PLL.

Alginates↗

Factors influencing the adequacy of microencapsulation of rat pancreatic islets.

The observation that only a portion of all alginate-polylysine microcapsules are overgrown after implantation suggests that physical imperfections of individual capsules, rather than the chemical composition of the material applied, are responsible for inducing insufficient biocompatibility and thereby fibrotic overgrowth of those capsules. We recently developed a lectin binding assay that allows for quantifying the portion of inadequately encapsulated islets, and demonstrated that inadequately encapsulated islets induce a fibrotic response associated with graft failure. The present study investigates factors influencing the adequacy of encapsulation of pancreatic islets. We applied our lectin binding assay and found that the number of inadequate, and particularly incomplete, capsules is influenced by the following factors. (1) A capsule diameter of 800 micrometers is associated with a lower percentage of inadequate capsules than smaller (500 micrometers and 600 micrometers) or larger (1800 micrometers) capsules. (2) A high rather than low guluronic acid content of the alginate is associated with a lower percentage of inadequate capsules. This can be explained, at least in part, by smaller ranges of swelling and subsequent shrinkage during the encapsulation procedure. (3) An increase in viscosity caused by applying a higher alginate concentration compensates for a low guluronic acid content. This effect of increased viscosity cannot be explained by a reduced range of swelling and shrinkage during the encapsulation procedure. We conclude that alginates with a high guluronic acid content and a viscosity near the filtration limit are preferable in order to minimize the number of inadequate capsules.

Alginates↗

Association between capsule diameter, adequacy of encapsulation, and survival of microencapsulated rat islet allografts.

As a consequence of its large volume, a microencapsulated islet graft can be implanted only into the peritoneal cavity. The graft volume can be reduced by using small capsules. However, reduction of the diameter of the capsules holds a certain risk, because with smaller capsules, more islets may be found to protrude from the capsules. We have developed a lectin binding assay which, after encapsulation, specifically labels islets or parts of islets that are insufficiently immunoprotected as a consequence of inadequate, and particularly incomplete, encapsulation. With this assay, we found that a reduction of the capsule diameter from 800 micrometers to 500 micrometers was associated with an increase in the percentage of inadequately encapsulated islets from 6.3+/-1.2% to 24.2+/-1.5%. The in vivo significance of this finding was investigated by performing allotransplantations with large diameter (700-800 micrometers) and small diameter (400-500 micrometers) capsules. With large-capsule islet grafts, all recipients (n=5) became normoglycemic for 7-16 weeks, whereas with small-capsule islet grafts, only one of seven recipients became normoglycemic. The in vivo significance of inadequate encapsulation was further substantiated by our finding that most large capsules were floating freely in the peritoneal cavity without any cell adhesion, whereas the vast majority of small capsules was found to be adherent to the surface of intra-abdominal organs and infiltrated by immune cell elements characteristic of both an allograft reaction and a foreign body reaction. We conclude that successful use of capsules with small diameters requires further study to determine which factors in the encapsulation procedure should be modified to reduce the number of inadequate small capsules.

Animals↗