Polymeric Approaches to Reduce Tissue Responses Against Devices Applied for Islet-Cell Encapsulation

Abstract

Immunoisolation of pancreatic islets is a technology in which islets are encapsulated in semipermeable but immunoprotective polymeric membranes. The technology allows for successful transplantation of insulin-producing cells in the absence of immunosuppression. Different approaches of immunoisolation are currently under development. These approaches involve intravascular devices that are connected to the bloodstream and extravascular devices that can be distinguished in micro- and macrocapsules and are usually implanted in the peritoneal cavity or under the skin. The technology has been subject of intense fundamental research in the past decade. It has co-evolved with novel replenishable cell sources for cure of diseases such as Type 1 Diabetes Mellitus that need to be protected for the host immune system. Although the devices have shown significant success in animal models and even in human safety studies most technologies still suffer from undesired tissue responses in the host. Here we review the past and current approaches to modulate and reduce tissue responses against extravascular cell-containing micro- and macrocapsules with a focus on rational choices for polymer (combinations). Choices for polymers but also choices for crosslinking agents that induce more stable and biocompatible capsules are discussed. Combining beneficial properties of molecules in diblock polymers or application of these molecules or other anti-biofouling molecules have been reviewed. Emerging are also the principles of polymer brushes that prevent protein and cell-adhesion. Recently also immunomodulating biomaterials that bind to specific immune receptors have entered the field. Several natural and synthetic polymers and even combinations of these polymers have demonstrated significant improvement in outcomes of encapsulated grafts. Adequate polymeric surface properties have been shown to be essential but how the surface should be composed to avoid host responses remains to be identified. Current insight is that optimal biocompatible devices can be created which raises optimism that immunoisolating devices can be created that allows for long term survival of encapsulated replenishable insulin-producing cell sources for treatment of Type 1 Diabetes Mellitus.

Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound

“…Given our in vitro data, it is likely that pFUS is working to both stimulate islets directly as well as indirectly through the stimulation of AD-MSCs which are coated onto the surface of islets. In addition, the alginate capsule will likely also protect the transplanted islets from direct effects of inflammation as well as any host-mediated response [ 87 ]. In future, additional studies will examine apoptosis and proliferation within transplanted islets using TUNEL and Ki67 assays.…”

Cell Encapsulation Within Alginate Microcapsules: Immunological Challenges and Outlook

“…The first contact of the capsule with the host occurs at the level of the polymer protecting the encapsulated cells (Figure 1). Next, the encapsulated cells themselves play a key role in inducing immune responses through antigen shedding and secretion of soluble immune mediators (Hu and de Vos, 2019; Figure 1). Additionally, the transgenes expressed and secreted by the encapsulated cells are often recognized as foreign by the host, while the expression vector used to genetically engineer encapsulated cells may contain immunogenic sequences and moieties.…”

“…Although numerous polymers have been described to protect encapsulated allo- or xenogeneic cells (de Vos et al, 2014; Hu and de Vos, 2019), alginate has been used the most, either alone or in combination with other polymers (de Vos et al, 2006; Goh et al, 2012). Alginate is a natural polysaccharide purified from algae (though it can also be produced by some bacteria), with excellent biocompatibility and biodegradability (Murua et al, 2008; Lee and Mooney, 2012; Gasperini et al, 2014) and a sound safety record (Orive et al, 2006).…”

Recent Advances in Micro-Electro-Mechanical Devices for Controlled Drug Release Applications

“…The design and development of novel materials and devices for medicine is one of the exciting new areas of bioengineering and biotechnology, which is rapidly gaining the attention of the scientific community (Zhang et al, 2011;Hardy et al, 2013;Copes et al, 2019;Hu and de Vos, 2019;Tamay et al, 2019). Biofabrication is providing scientists and clinicians the ability to produce engineered devices with desired shapes, chemical composition, and biological functions (Echave et al, 2019;Scilletta et al, 2019;Debons et al, 2020;Frayssinet et al, 2020).…”