A scalable device-less biomaterial approach for subcutaneous islet transplantation

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.SummaryIn 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.

Phosphorylcholine- and cation-bearing copolymer coating with superior antibiofilm and antithrombotic properties for blood-contacting devices

The phosphorylcholine- and cation-bering copolymer coating endowed the blood-contacting devices with superior antibiofilm and antithrombotic ability.

Biocompatibility of a polymer-coated membrane possessing a hydrophilic blood-contacting layer: Adsorption-related assessment

Objective: Currently, the foreign surfaces of extracorporeal circulation devices are coated with an acrylate-based copolymer that creates a hydrophilic blood-contacting layer to enhance biocompatibility. Several reports of acrylate-based copolymer with respect to biocompatibility have been published; however, the adsorption of peptide compounds on acrylate-based copolymer–coated membranes still requires clarity. In this study, we aimed to understand the adsorption of several peptide compounds of various molecular weights, including albumin, lysozyme, and vancomycin, on acrylate-based copolymer–coated membranes using in vitro studies. Methods: Six experimental circuits consisting of acrylate-based copolymer–coated tubes and membranes, and six comprising acrylate-based copolymer–coated tubes and non-coated membranes were prepared for comparison. An experimental solution, composed of albumin, lysozyme, vancomycin, and saline, was continuously stirred in a reservoir, recirculated in each experimental circuit, and then filtered. Concentrations of albumin, lysozyme, and vancomycin were measured after 0, 15, 30, 45, 60, 90, and 120 min of recirculation. Similar experiments were performed in all the prepared circuits. Results: The ratio of measured values at each time point to those at 0 min was not significantly different between acrylate-based copolymer–coated and non-coated membranes for albumin and lysozyme, but differed significantly for vancomycin; the ratios were higher in acrylate-based copolymer–coated than in non-coated membranes. Conclusion: This study suggests that albumin is not adsorbed on either acrylate-based copolymer–coated or non-coated membranes, that lysozyme is not adsorbed on either membrane or is adsorbed at a similar rate on both membranes, and that vancomycin is less adsorbed on acrylate-based copolymer–coated membranes. Thus, acrylate-based copolymer coating could inhibit the adsorption of various peptide compounds.