ENGINEERED SCALE-UP OF NEOCARTILAGE FABRICATION FOR NASAL SEPTAL RECONSTRUCTION POST RADICAL RESECTION

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2013-04-12

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Lin, Victor

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Purpose: In the setting of tissue scarcity and reconstructive rhinoplasty for the repair of craniofacial traumas, intrusive lesions, and congenital deformities, tissue engineering efforts were aimed to improve current tissue generation and match native cartilage properties for restoring damaged facial regions. This study was designed to assess 2 membrane-based constructs for scale-up in neocartilage production of the whole septum, with expectations that tissues generated from polycarbonate membranes in transwell cartilage development would functionally match those derived in polyethylene membrane (industry standard) based experiments. Additionally, 3 micron pores were assessed, with expectations that larger pore sized transwells would provide improved nutrient transport and enhanced cartilage mechanics compared to conventional 0.4 micron pores. Methods: Septal cartilage was harvested from human donors and isolated for chondrocyte expansion. Monolayers were matured in alginate beads, recovered by ARC method, and cells further developed on polycarbonate (PC) and polyethylene (PE) membranes of 3 and 0.4 microns. The neocartilage fabrications were matured in ARC reactors and tested for thickness, COL:sGAG, tensile peak stress and tensile stiffness at failure strain. Results: 3um PE and PC, and 0.4um PE and PC constructs were compared to native tissue and ANOVA tested. All constructs had comparable thickness to native, with no p-value significantly different from native (p<0.005). 3umPE (p=0.008) and 3umPC (p=0.005) significantly resembled native for COL:sGAG, while 0.4umPE and PC constructs did not (p=0.002 and p=0). 3umPE and 3umPC constructs generated tensile peak stresses similar to native (p=0.053 and 0.059), while 0.4umPE and PC constructs significantly differed from native (p=0.004 and 0.003). Measuring tensile stiffness at failure strain showed only 3umPC generated forces significantly close to native (p=0.252). Conclusions: Compared to conventional tissue fabrication using 0.4PE membranes, PC membrane-based constructs provide a viable and superior substrate for neocartilage development. Furthermore, larger membrane pores at 3um generate constructs closer to native tissue. The combination of PC and 3um pore size is ideal for upscale neocartilage fabrication, generation of cartilage tissue that more closely resembles cartilage tissue (biochemically, histologically, and mechanically) than ever before, and the ability to create tissue for large defect cartilage reconstruction and/or repair.

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