Supermacroporous cryogels as scaffolds for pancreatic islet transplantation

Clinical islet transplantation is a promising approach in treating Type 1 diabetes and a subgroup of patients with Type 2 diabetes requiring insulin administration. Currently, there are several limitations for long-term engraftment of functional islets: Immune rejection, inadequate oxygen and nutrient supply, as well as inefficient metabolic waste removal from grafted endocrine tissue. To overcome such limitations, a tissue engineering approach based on utilization of three-dimensional (3D) supermacroporous scaffolds was developed. The main aim of using 3D scaffolds is to supply the grafted islets with a matrix that can promote local neovascularisation and support long-term survival and functional activity of the cells. Among the many approaches to construct such a bioengineered tissue construct, alginate- and agarose-based supermacroporous cryogels, manufactured by cryotropic gelation, showed several advantages. The unique interconnected pore structure of these biocompatible cryogels, in combination with their osmotic, chemical and mechanical stability, renders them as attractive matrices for the immobilization of biomolecules, hence facilitating cell attachment and enhancement of neovascularisation. In addition, cryogels are able to serve as a scaffold to support cell populations, such as mesenchymal stem/stromal cells (MSCs). These cell populations are of crucial importance to the field of tissue transplantation as they have been shown to attenuate immune rejection and secrete angiogenic, anti-inflammatory and anti-apoptotic factors. In addition, the unique properties of the supermacroporous cryogels enable the use of cryopreservation technologies to be used as an 'off-the-shelf' ready-to-use bio-artificial supporting system for further pancreatic islet transplantations.