Biocompatibility of Alginates for Grafting: Impact of Alginate Molecular Weight

Abstract

Optimising microencapsulation technology towards the effective clinical transplantation has created the need for highly biocompatible alginates. Therefore, in this study the biocompatibility of different beads prepared from alginates with varying average molecular weight was examined. In some experiments the beads were covered with a multilayer membrane surrounded by an alginate layer. First of all, we found that beads made of a lower weight average alginate elicted a much stronger fibrotic response compared to beads made of a higher weight average alginate (LV-alginate > MV-alginate). The results were confirmed by the observation that the extent of tissue fibrosis was significantly increased in multilayer capsules made of an alginate with a lower weight average (core and surface LV-alginate, Mw 0.7-1 * 10(6) g/mol, viscosity of a 0.1% solution 1-2.5 mPa s(-1)) compared to multilayer capsules made of an alginate with a higher weight average (core and surface MV-alginate; Mw 1.2-1.3 * 10(6) g/mol, viscosity of a 0.1% solution 5-7 mPa s(-1)). It should be stressed, that the pro-fibrotic effect of the LV-alginate alginate in the core was only partially reversed by a MV-alginate on the surface of the multilayer capsules. On the basis of the raised data, it can be assumed that the molecular weight average of the alginates have an decisive effect on the biocompatibility. Therefore, it seems to be recommendable to reduce the low molecular weight fractions of the alginate during the purification process to improve the biocompatibility.

Quantitative analysis of fibrosis formation on the microcapsule surface with the use of picro‐sirius red staining, polarized light microscopy, and digital image analysis

“…Zhang and co‐workers have determined the degree of FO by measuring the thickness of the pericapsular fibrotic layer, as indicated by Goldner staining 23, 24. Similarly, Schneider et al have adopted the fibrotic area per capsule (in μm2) to indicate the severity of fibrotic reaction 25. In addition, other parameters, such as the retrieval rate of microcapsules and the percentage of microcapsules with overgrowth, served as indexes of severity of FO 26…”

“…Schneider utilized Photoshop software for objective quantification of FO, and fibrotic area per capsule was served as one index of severity of FO;25 however, the method was time‐consuming, because it manually processed only one image at a time and was impossible to process in batches. In the present study, a macro was created with the use of Image‐Pro Plus software.…”

Long-Term Graft Function of Adult Rat and Human Islets Encapsulated in Novel Alginate-Based Microcapsules After Transplantation in Immunocompetent Diabetic Mice

“…The abdomen was sutured and the animals were checked daily for blood glucose concentrations. Explanted microcapsules were evaluated for fibrotic overgrowth under a Wilowert S microscope (Hund GMBH, Wetzlar, Germany), as previously described (21). Images were captured with a digital camera and stored as jpg files.…”

Purification of Alginate for Tissue Engineering

“…It was also reported that molecular weight may influence the in vitro and in vivo response to alginate gel and capsules [21]. So we observed the purification process induces a change in the viscosity-average molecular weight of alginate.…”