Microencapsulation of beta cells in collagen micro-disks via circular pneumatically actuated soft micro-mold (cPASMO) device

Abstract

The artificial pancreas provides a method for automatically managing insulin concentrations in patients with Type I diabetes. One strategy for fabricating an artificial pancreas is the encapsulation of beta cells in a collagen matrix, which can provide mechanical support. In addition, encapsulation of beta cells in small volumes and with high surface areas allows them to quickly sense glucose and secrete insulin for regulation. Currently, there is no such fabrication technique of encapsulating beta cells in a collagen matrix, due to their inherent fragility. Herein, we develop a novel technique called circular Pneumatic Actuated Soft Micromold (cPASMO) to produce collagen microdisks for encapsulating beta cells. cPASMO consists of a particle template, pneumatic channel, and buffer layer to control deformation. The actuation mechanism is simply to deform the template by increasing the inner pressure inside the channel. This deformation in the template generates a gap between the collagen microdisks and mold that can extract the collagen microdisks via buoyancy force. Thus, they can be released from their templates without damage. The position of the air channel determines the uniformity of the template deformation that leads to the high collagen microdisk extraction rate. Compared to the previous design (i.e., linear air channel), the extraction rate is four times faster. We demonstrated that beta cells encapsulated in collagen micro disks by a cPASMO device exhibit a biological function of rapidly sensing glucose and secreting insulin for regulation. The concentration of the secreted insulin from the encapsulated beta cells is three to six times higher than that of suspended cells. Also, smaller collagen micro disks release higher concentrations of insulin than those that are larger because the larger spaces between beta cells can degrade cellular communication. These breakthroughs in producing collagen microdisks will push the boundaries of treatment for Type I diabetic patients.