Genipin-crosslinked double PLL membranes overcome the strength-diffusion trade-off in cell encapsulation without compromising biocompatibility

Abstract

Cell microencapsulation technologies allow non-autologous implantation of therapeutic cells for sustained drug delivery purposes. The perm-selective membrane of these systems provides resistance to rupture, stablishes the upper molecular weight limit in bidirectional diffusion of molecules, and affects biocompatibility. Thus, despite being a decisive factor to succeed in terms of biosafety and therapeutic efficacy, little progress has been made in its optimization so far. Here we show that, compared to other usually used coating designs, genipin-crosslinked double poly-L-lysine (GDP) membranes are able to simultaneously improve mechanical and mass-transport properties of the microcapsules, without causing any significant increase in the foreign body response when implanted in vivo. In particular, we show that GDP membranes confer capsular integrity under high pressures, both internal and external. Furthermore, this membrane design allows for more efficient bidirectional diffusion of molecules in the 20–40 kDa range while preserving the molecular weight cut-off required for exerting an effective immunobarrier. These findings may also be useful for optimizing the membrane characteristics of multiple drug delivery systems