Project Design Specifications Team Albert Kwansa John Harrison Yik Ning Wong Eric Lee Problem Statement A method of treatment for various endocrine diseases incorporates the encapsulation of cells and tissues and the time released delivery of chemical mediators Presently this method encounters a slew of problems including a lack of biocompatibility limited immunoprotective properties and hypoxia The client desires the development of microcapsules that would permit the successful release of hormones namely testosterone and inhibin by encapsulated cells into animals while avoiding the aforementioned problems Function The resulting microcapsules should allow transplantation of hormone releasing tissue without the use of immunosuppressant drugs by providing a mechanical barrier to immune system attack Client requirements Microencapsulation of Murine Leydig Tumor Cells Type 1 MLTC 1 Must release hormones of interest testosterone and inhibin over time while keeping harmful molecules antibodies etc out Biocompatible immunoprotective minimize mechanical and chemical degradation Design requirements Physical and operational characteristics a Viability the encapsulation process may have adverse effects on initial cell b c d e viability in microcapsules The proposed design should retain at least 75 cell viability measured 1d post encapsulation using a Cell Titer Blue assay Hormone release normal values of testosterone in human males ranges from 2 to 12 ng mL Degradation the biomaterial Polyethylene glycol PEG should remain intact long enough to sustain a critical cell mass such to provide adequate hormone release for at least six months Capsule size various thickness of the PEG will be tested experimentally to determine the optimal range of capsule diameter Molecular weight cutoff MWCO MWCO should be 75kDa in order to allow diffusion of relevant molecules specifically testosterone 300 Da inhibin 32 kDa activin LH 30 kDa FSH 36 kDa but block out human antibodies IgG 150 kDa f Immune response microcapsules must not allow the diffusion of antibodies or g h i j immune system cells by providing a sufficiently small mesh size Biocompatibility biomaterial PEG and its degradation products must be nontoxic and not cause inflammation within the body Injected microcapsules must resist protein adsorption and fibroblast overgrowth Life in service therapy should sustain patient at minimum serum testosterone concentration 2 ng mL for at least 6 months Production timeframe microencapsulated cell therapy at present will be prepared from start to finish as needed by patient demand Microencapsulated cells will be implanted soon after production The microencapsulated cells should be sustainable in vitro for at least several days Operating environment in vitro site of implantation to be determined Subcutaneous and intraperitoneal injections are both possible Machluf et al 2003 Product characteristics a Quantity thousands to hundreds of thousands of microcapsules will be required per injection The cell mass required to provide adequate hormone release is currently unknown but likely on the order of 106 cells b Sterility final product must be sterile prior to implanatation c Target product cost not specified d Research costs unknown Miscellaneous a Standard and specifications FDA approval is required University approval required prior to animal or human subject testing b Competition Several patents regarding cell encapsulation exist and define specific production protocols These are US Patent 5 762 959 US Patent 5 100 673 and US Patent 5 164 126 This study is not expected to infringe upon past technology as a novel capsule design is desired
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