Contribution of polymeric materials to progress in xenotransplantation of microencapsulated cells: a review

Abstract

Cell microencapsulation and subsequent transplantation of the microencapsulated cells require multidisciplinary approaches. Physical, chemical, biological, engineering, and medical expertise has to be combined. Several natural and synthetic polymeric materials and different technologies have been reported for the preparation of hydrogels, which are suitable to protect cells by microencapsulation. However, owing to the frequent lack of adequate characterization of the hydrogels and their components as well as incomplete description of the technology, many results of in vitro and in vivo studies appear contradictory or cannot reliably be reproduced. This review addresses the state of the art in cell microencapsulation with special focus on microencapsulated cells intended for xenotransplantation cell therapies. The choice of materials, the design and fabrication of the microspheres, as well as the conditions to be met during the cell microencapsulation process, are summarized and discussed prior to presenting research results of in vitro and in vivo studies. Overall, this review will serve to sensitize medically educated specialists for materials and technological aspects of cell microencapsulation.

Update on cellular encapsulation

“…The limitations of alginate encapsulation have led to the pursuit of suitable synthetic materials which can be reproducibly manufactured and tailored to specific biological applications. Although this has proven historically challenging as many of the materials and processes involved in synthetic capsule manufacturing have been costly or cytotoxic, several promising alternatives have emerged . In particular, polyethylene glycol (PEG) hydrogels have been extensively studied and demonstrated excellent biocompatibility and versatility .…”

“…Multicomponent capsules have been used to customize the properties of implants to specific biological needs . For example, polycation with poly‐L‐lysine or poly‐L‐ornithine coatings can reduce porosity and improve the mechanical stability of alginate capsules . While poly‐L‐lysine can provoke inflammation, a final outer alginate layer or the addition of PEG can ameliorate this effect .…”

“…Although this has proven historically challenging as many of the materials and processes involved in synthetic capsule manufacturing have been costly or cytotoxic, several promising alternatives have emerged. 102,113 In particular, polyethylene glycol (PEG) hydrogels have been extensively studied and demonstrated excellent biocompatibility and versatility. 114 PEG can be applied using a layer by layer method to achieve nanoscale thickness coating, and like alginate, it is compatible with modern encapsulation techniques such as electrohydrodynamic spraying and 3D bioprinting.…”

“…73,116,[122][123][124][125][126] For example, polycation with poly-L-lysine or poly-L-ornithine coatings can reduce porosity and improve the mechanical stability of alginate capsules. 104,113,[127][128][129][130] While poly-L-lysine can provoke inflammation, a final outer alginate layer or the addition of PEG can ameliorate this effect. 124,130 These capsules have been effective at significantly delaying the humoral response to xenografted tissue.…”

Xenotransplantation

“…The microencapsulated porcine hepatocytes provided temporary functional support [61]. Mahou et al reviewed the contribution of polymeric materials in the xenotransplantation of microencapsulated cells (mainly hepatocytes and islets), and addressed the state-of-the-art in cell microencapsulation with special focus on the choice of materials, and the design and fabrication of the microspheres [62]. Iwase et al transplanted genetically-engineered pig hepatocytes directly into the spleen and other sites in immunosuppressed baboons, and reported very early graft failure [63].…”