A scalable device-less biomaterial approach for subcutaneous islet transplantation

Abstract The subcutaneous space has been shown to be a suitable site for islet transplantation, however an abundance of islets is required to achieve normoglycemia, often requiring multiple donors. The loss of islets is due to the hypoxic conditions islets experience during revascularization, resulting in apoptosis. Therefore, to reduce the therapeutic dosage required to achieve normoglycemia, pre-vascularization of the subcutaneous space has been pursued. In this study, we highlight a biomaterial-based approach using a methacrylic acid copolymer coating to generate a robust pre-vascularized subcutaneous cavity for islet transplantation. We also devised a simple, but not-trivial, procedure for filling the cavity with an islet suspension in collagen. We show that the pre-vascularized site can support a marginal mass of islets to rapidly return streptozotocin-induced diabetic SCID/bg mice to normoglycemia. Furthermore, immunocompetent Sprague Daley rats remained normoglycemia for up to 70 days until they experienced graft destabilization as they outgrew their implants. This work highlights methacrylic acid-based biomaterials as a suitable pre-vascularization strategy for the subcutaneous space that is scalable and doesn’t require exogenous cells or growth factors. Summary In this study methacrylic acid copolymer coated tubes generated a robust vascular response in the subcutaneous space, which was critical to support islet transplantation in a streptozotocin-induced diabetic mouse model. More importantly, the subcutaneous pre-vascularization approach using this copolymer coating was scalable into a larger allogeneic rat model and returned animals to normoglycemia for up to 70 days. This platform highlights the potential of a scalable biomaterial approach for pre-vascularization of the subcutaneous space in larger animal models.