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  Cornell University

MAE Publications and Papers

Sibley School of Mechanical and Aerospace Engineering

New article: Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific Auricles In Vivo

Article: Cohen, BP; Hooper, RC; Puetzer, JL; Nordberg, R; Asanbe, O; Hernandez, KA; Spector, JA; Bonassar, LJ; (2016)  “Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific Auricles In Vivo”, Tissue Engineering Part A, 22 (5-6): 461-468

DOI

Abstract:  Current techniques for autologous auricular reconstruction produce substandard ear morphologies with high levels of donor-site morbidity, whereas alloplastic implants demonstrate poor biocompatibility. Tissue engineering, in combination with noninvasive digital photogrammetry and computer-assisted design/computer-aided manufacturing technology, offers an alternative method of auricular reconstruction. Using this method, patient-specific ears composed of collagen scaffolds and auricular chondrocytes have generated auricular cartilage with great fidelity following 3 months of subcutaneous implantation, however, this short time frame may not portend long-term tissue stability. We hypothesized that constructs developed using this technique would undergo continued auricular cartilage maturation without degradation during long-term (6

month) implantation. Full-sized, juvenile human ear constructs were injection molded from high-density collagen hydrogels encapsulating juvenile bovine auricular chondrocytes and implanted subcutaneously on the backs of nude rats for 6 months. Upon explantation, constructs retained overall patient morphology and displayed no evidence of tissue necrosis. Limited contraction occurred in vivo, however, no significant change in size was observed beyond 1 month. Constructs at 6 months showed distinct auricular cartilage microstructure, featuring a self-assembled perichondrial layer, a proteoglycan-rich bulk, and rounded cellular lacunae. Verhoeff’s staining also revealed a developing elastin network comparable to native tissue. Biochemical measurements for DNA, glycosaminoglycan, and hydroxyproline content and mechanical properties of aggregate modulus and hydraulic permeability showed engineered tissue to be similar to native cartilage at 6 months.

Patient-specific auricular constructs demonstrated long-term stability and increased cartilage tissue development during extended implantation, and offer a potential tissue-engineered solution for the future of auricular reconstructions.

Funding Acknowledgement:  NIH [5T35EB006732]; NYSTAR; 3D BioCorp

Funding Text:  Funding for this research was provided by NIH Grant 5T35EB006732, NYSTAR, and 3D BioCorp. This work was presented in part at the Northeastern Society of Plastic Surgeons 28th Annual Meeting in Amelia Island, FL, the Plastic Surgery Research Council 57th and 60th Annual Meetings in Ann Arbor, MI, and Seattle, WA, respectively, the American Society of Plastic Surgeons 2012 Annual Meeting in New Orleans, LA, the American Society for Reconstructive Microsurgery 2013 and 2015 Annual Meetings in Naples, FL, and Paradise Island, BS, and the Biomedical Engineering Society 2014 Annual Meeting in San Antonio, TX.

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