An Investigation of Nano-structured Polymers for Use as Bladder Tissue Replacement Constructs
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An Investigation of Nano-structured Polymers for Use as Bladder Tissue Replacement Constructs
Anil Thapa, Thomas J. Webster, and Karen M. Haberstroh Department of Biomedical Engineering Purdue University, West Lafayette, Indiana 47907-1296
ABSTRACT Conventionally, studies investigating the design of synthetic bladder wall substitutes have involved polymers with micro-dimensional structures. Since the body is made up of nanostructured components (e.g., extracellular matrix proteins), our focus has been in the use of nanostructured polymers in order to design a three-dimensional synthetic bladder construct that mimics bladder tissue in vivo. In order to complete this task, we fabricated novel, nanostructured, biodegradable materials to serve as substrates for bladder tissue constructs and tested the cytocompatibility properties of these biomaterials in vitro. The results from our in vitro work to date have provided the first evidence that cellular responses (such as adhesion and proliferation) of bladder smooth muscle cells are enhanced as poly (lactic-co-glycolic acid) (PLGA) surface feature dimensions are reduced into the nanometer range.
INTRODUCTION Urinary bladder cancer is the second most common malignancy of the genitourinary tract and the fourth leading cause of cancer among American men [1]. The major form is superficial and accounts for 75-85 % of all bladder cancers [2]. Therapeutic approaches and prognosis of the disease have been less than ideal, possibly for the following reasons: a. Insufficient knowledge of the cellular/molecular level events occurring within normal/pathological bladder tissue; b. Inability to simulate in vivo properties of bladder wall tissue in vitro; and c. Inability to design bladder replacements with similar material and mechanical properties to bladder wall tissue. The most successful approach to treatment of superficial bladder cancer has been transurethral resection of the cancerous portion of the bladder wall combined with adjuvant intravesical immuno-chemotherapy [3]; in order to patch the resected portion of the bladder wall, it is necessary to design a bladder replacement-implant. To date, there have been several complications involved in both synthetic and biological replacement approaches. For example, biological implants suffer from host-to-graft rejection responses, unavailability of donors, infection, ethical issues (concerning the sacrifice of animals or use of animal tissues for implantations), etc. Complications with synthetic approaches include infection, toxicity, issues of biocompatibility and cytocompatibility, etc. Unfortunately, to date, a successful implant has not been reported which addresses all of these issues. Previous work in the area of tissue-construct implantations has involved the use of matrices derived from natural extra-cellular proteins such as collagen; these scaffolds are limited by their GG3.4.1
poor mechanical stability, can provoke adverse tissue and immune responses, and may elicit undesired cell behavior [4]. Some of the alloplastic
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