ABSTRACT
Immunoisolation strategies have the potential to impact the treatment of several diseases, such as hemophilia, Parkinson's and endocrine disorders, such as parathryroid disorders and diabetes. The hallmark of these disease states is the amelioration of the disease process by replacement of the deficient protein. Naturally, several cellular therapeutic strategies like genetically modified host cells, stem cells, donor cells, or even complex tissues like pancreatic islets have been investigated. Current evidence suggests that successful strategies must incorporate considerations for local hypoxia, vascularity, and immunoisolation. Additional regulatory concerns also include safe localization of implanted therapeutic cells to allow for monitoring, dose adjustment, or removal when indicated. Local hypoxia and cellular toxicity can be detrimental to the survival of freshly implanted pancreatic islets, leading to a need for a larger initial number of islets or repeated implantation procedures. The lack of adequate donors and the large number of islet equivalents needed to achieve euglycemic states amplify the nature of this problem. We have developed a novel immunoisolation device based on electrospun nylon, primarily for islet transplantation, such that the inner component functions as a cellular barrier while allowing diffusion, whereas the outer component can be optimized for tissue integration and accelerated vascularization. Devices explanted after subcutaneous implantation in wild-type B6 mice after a period of 30 days show vascular elements in the outer layer of the electrospun device. The inner layer when intact functioned as an effective barrier to cellular infiltration. The preimplantation of such a device, with a relatively thin inner barrier membrane, will allow for adequate vascularization and reduce postimplantation hypoxia. This study demonstrates the feasibility of an electrospun isolation device that can be easily assembled, modified by varying the electrospinning parameters, and functionalized with surface-active molecules to accelerate vascularization.
Subject(s)
Cell Separation/methods , Islets of Langerhans Transplantation/methods , Animals , Cell Culture Techniques , Cell Separation/instrumentation , Cell-Derived Microparticles , Hypoxia , Immunohistochemistry/methods , Insulin/metabolism , Islets of Langerhans Transplantation/instrumentation , Membranes, Artificial , Mice , Microscopy, Electron, Scanning/methods , Porosity , Transplantation, Heterologous/methodsABSTRACT
We characterize the infiltration of interstitial cells into tissue engineering scaffolds prepared with electrospun collagen, electrospun gelatin, electrospun poly(glycolic) acid (PGA), electrospun poly(lactic) acid (PLA), and an electrospun PGA/PLA co-polymer. Electrospinning conditions were optimized to produce non-woven tissue engineering scaffolds composed of individual fibrils less than 1000 nm in diameter. Each of these materials was then electrospun into a cylindrical construct with a 2 mm inside diameter with a wall thickness of 200-250 microm. Electrospun scaffolds of collagen were rapidly, and densely, infiltrated by interstitial and endothelial cells when implanted into the interstitial space of the rat vastus lateralis muscle. Functional blood vessels were evident within 7 days. In contrast, implants composed of electrospun gelatin or the bio-resorbable synthetic polymers were not infiltrated to any great extent and induced fibrosis. Our data suggests that topographical features, unique to the electrospun collagen fibril, promote cell migration and capillary formation.
Subject(s)
Biocompatible Materials/chemistry , Electrochemistry/methods , Lactic Acid/chemistry , Muscle Fibers, Skeletal/physiology , Nanotubes/chemistry , Polyglycolic Acid/chemistry , Polymers/chemistry , Tissue Engineering/methods , Animals , Cell Adhesion/physiology , Cell Culture Techniques/methods , Cell Movement/physiology , Cells, Cultured , Materials Testing , Nanotubes/ultrastructure , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Rats, Sprague-Dawley , RotationABSTRACT
Three different bileaflet mechanical heart valves were evaluated for wear and durability characterization. The designs of the three mechanical heart valves encompass both geometrical and material interface differences. The St. Jude Medical mechanical heart valve is partially characterized by a flat-on-flat leaflet-to-orifice closing stop interface with the orifice constructed of a graphite substrate with pyrolytic carbon coating. The CarboMedicsTM mechanical heart valve is partially characterized by a flat-on-cylindrical leaflet-to-orifice closing stop interface and the orifice is constructed of solid pyrolytic carbon. The Sorin Biomedica BicarbonTM mechanical heart valve is characterized by a flat-on-flat leaflet-to-orifice closing stop interface with the leaflets constructed of pyrolytic carbon and the orifice constructed of a titanium alloy. In vitro mechanical wear analysis was performed in accordance with current FDA and ISO guidelines for accelerated life and durability testing. Comparisons revealed that the St. Jude Medical mechanical heart valve had the lowest magnitude of wear, but both the St. Jude Medical and CarboMedics mechanical heart valves proved to be very wear resistant. The Sorin Biomedica Bicarbon mechanical heart valve showed an extremely high wear rate and magnitude. The overall mechanism for material removal and wear must be fully determined to assess the long term efficacy of the mechanical heart valve.
