Y using injection molded collagen implants showed similar results after only 3 months in vivo. Despite its initial success, our technique would require modifications prior to translation to human subjects. An immunocompromised host was 
utilized in this study, and therefore the constructs implanted were not necessarily subject to the same degree of scaffold degradation, inhibitor vascularization, or host cell invasion as would be seen in immunocompetent models. The 18325633 immune response to both cellular and acellular scaffolds therefore necessitates evaluation in an immunocompetent host, as one could theoretically be 22948146 mounted against either non-autologous collagen or cellular inhabitants. In Epigenetic Reader Domain addition, the chondrocytes utilized in this study were of bovine 
origin. However, to facilitate translation to the clinical realm, the identical methodology could be applied using patient-specific chondrocytes derived from the patient’s own microtic ear remnant, or potentially even autologous bone marrow- or adipose-derived mesenchymal stem cells, or some combination thereof. This substitution would eliminate the immune response to non-autologous cells within the construct. Non-autologous collagen (i.e., bovine and porcine) is already commonly utilized for clinical purposes, is well tolerated as such, and therefore is of less concern as a potential antigenic stimulus. Lastly, although it is unlikely that construct degradation would occur beyond 3 months, verification of construct stability over a longer implantation interval (i.e., 6?2 months) must be performed.ConclusionsDigital photogrammetry was successfully combined with CAD/ CAM and tissue injection molding techniques to create highfidelity, biocompatible, patient-specific tissue-engineered constructs for auricular reconstruction without the use of imaging modalities that incur ionizing radiation. We believe that our cellular constructs’ appropriate biomechanical properties and maintenance of volume, shape and topographical characteristics over time can be attributed in part to their type I collagen hydrogel composition, which allows for the optimal rates of chondrocyte growth, matrix resorption, and the in vivo deposition of elastic cartilage. Although this strategy holds immense potential for tissue-engineered auricular reconstructions, construct evolution over a longer implantation interval (i.e., 6?2 months) and ultimately, use of patient-specific chondrocytes and/or mesenchymal stem cells must be evaluated prior to translation of this technology to the clinical realm.AcknowledgmentsWe are exceedingly grateful to Mr. and Mrs. Joseph Wood for their generosity and support. The authors thank Prof. Donald P. Greenberg and Mr. Hurf Sheldon for their critical assistance and use of facilities to obtain high-resolution images of human ears. 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 Annual Meeting in Ann Arbor, MI, the American Society of Plastic Surgeons 2012 Annual Meeting in New Orleans, LA, andTissue Engineering of Patient-Specific Auriclesthe American Society for Reconstructive Microsurgery 2013 Annual Meeting in Naples, FL.Author ContributionsConceived and designed the experiments: AJR BNB LJB JAS. Performed the experiments: AJR CK KAH S. Popa JLP SZ S. Pramanik BNB WSR.Analyzed the data: AJR CK KAH S. Popa JLP SZ S. Pramanik BNB WSR LJB JAS. Contributed reagents/materials/analysis tools: LJ.Y using injection molded collagen implants showed similar results after only 3 months in vivo. Despite its initial success, our technique would require modifications prior to translation to human subjects. An immunocompromised host was utilized in this study, and therefore the constructs implanted were not necessarily subject to the same degree of scaffold degradation, vascularization, or host cell invasion as would be seen in immunocompetent models. The 18325633 immune response to both cellular and acellular scaffolds therefore necessitates evaluation in an immunocompetent host, as one could theoretically be 22948146 mounted against either non-autologous collagen or cellular inhabitants. In addition, the chondrocytes utilized in this study were of bovine origin. However, to facilitate translation to the clinical realm, the identical methodology could be applied using patient-specific chondrocytes derived from the patient’s own microtic ear remnant, or potentially even autologous bone marrow- or adipose-derived mesenchymal stem cells, or some combination thereof. This substitution would eliminate the immune response to non-autologous cells within the construct. Non-autologous collagen (i.e., bovine and porcine) is already commonly utilized for clinical purposes, is well tolerated as such, and therefore is of less concern as a potential antigenic stimulus. Lastly, although it is unlikely that construct degradation would occur beyond 3 months, verification of construct stability over a longer implantation interval (i.e., 6?2 months) must be performed.ConclusionsDigital photogrammetry was successfully combined with CAD/ CAM and tissue injection molding techniques to create highfidelity, biocompatible, patient-specific tissue-engineered constructs for auricular reconstruction without the use of imaging modalities that incur ionizing radiation. We believe that our cellular constructs’ appropriate biomechanical properties and maintenance of volume, shape and topographical characteristics over time can be attributed in part to their type I collagen hydrogel composition, which allows for the optimal rates of chondrocyte growth, matrix resorption, and the in vivo deposition of elastic cartilage. Although this strategy holds immense potential for tissue-engineered auricular reconstructions, construct evolution over a longer implantation interval (i.e., 6?2 months) and ultimately, use of patient-specific chondrocytes and/or mesenchymal stem cells must be evaluated prior to translation of this technology to the clinical realm.AcknowledgmentsWe are exceedingly grateful to Mr. and Mrs. Joseph Wood for their generosity and support. The authors thank Prof. Donald P. Greenberg and Mr. Hurf Sheldon for their critical assistance and use of facilities to obtain high-resolution images of human ears. 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 Annual Meeting in Ann Arbor, MI, the American Society of Plastic Surgeons 2012 Annual Meeting in New Orleans, LA, andTissue Engineering of Patient-Specific Auriclesthe American Society for Reconstructive Microsurgery 2013 Annual Meeting in Naples, FL.Author ContributionsConceived and designed the experiments: AJR BNB LJB JAS. Performed the experiments: AJR CK KAH S. Popa JLP SZ S. Pramanik BNB WSR.Analyzed the data: AJR CK KAH S. Popa JLP SZ S. Pramanik BNB WSR LJB JAS. Contributed reagents/materials/analysis tools: LJ.
