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Item Function‐Preserving Tailored Open Partial Laryngectomy for Chondrosarcoma of the Thyroid Ala: A Case Report(Sage, 2023-09-05) Farlow, Janice L.; Hogikyan, Norman D.; Morrison, Robert J.; Otolaryngology -- Head and Neck Surgery, School of MedicineItem Laryngeal Reconstruction Using Tissue-Engineered Implants in Pigs: A Pilot Study(Wiley, 2021-10) Brookes, Sarah; Zhang, Lujuan; Puls, Theodore J.; Kincaid, John; Voytik-Harbin, Sherry; Halum, Stacey; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective/hypothesis: There are currently no treatments available that restore dynamic laryngeal function after hemilaryngectomy. We have shown that dynamic function can be restored post hemilaryngectomy in a rat model. Here, we report in a first of its kind, proof of concept study that this previously published technique is scalable to a porcine model. Study design: Animal study. Methods: Muscle and fat biopsies were taken from three Yucatan minipigs. Muscle progenitor cells (MPCs) and adipose stem cells (ASCs) were isolated and cultured for 3 weeks. The minipigs underwent a left laterovertical partial laryngectomy sparing the left arytenoid cartilage and transecting the recurrent laryngeal nerve. Each layer was replaced with a tissue-engineered implant: 1) an acellular mucosal layer composed of densified Type I oligomeric collagen, 2) a skeletal muscle layer composed of autologous MPCs and aligned oligomeric collagen differentiated and induced to express motor endplates (MEE), and 3) a cartilage layer composed of autologous ASCs and densified oligomeric collagen differentiated to cartilage. Healing was monitored at 2 and 4 weeks post-op, and at the 8 week study endpoint. Results: Animals demonstrated appropriate weight gain, no aspiration events, and audible phonation. Video laryngoscopy showed progressive healing with vascularization and re-epithelialization present at 4 weeks. On histology, there was no immune reaction to the implants and there was complete integration into host tissue with nerve and vascular ingrowth. Conclusions: This pilot study represents a first in which a transmural vertical partial laryngectomy was performed and successfully repaired with a customized, autologous stem cell-derived multi-layered tissue-engineered implant.Item Stem cell-derived tissue-engineered constructs for hemilaryngeal reconstruction(Sage Publications, 2014-02) Halum, Stacey L.; Bijangi-Vishehsaraei, Khadijeh; Zhang, Hongji; Sowinski, John; Bottino, Marco C.; Department of Otolaryngology--Head and Neck Surgery, IU School of MedicineOBJECTIVES: As an initial step toward our goal of developing a completely tissue-engineered larynx, the aim of this study was to describe and compare three strategies of creating tissue-engineered muscle-polymer constructs for hemilaryngeal reconstruction. METHODS: Cartilage-mimicking polymer was developed from electrospun poly(D,L-lactide-co-ε-caprolactone) (PCL). Primary muscle progenitor cell cultures were derived from syngeneic F344 rat skeletal muscle biopsies. Twenty F344 rats underwent resection of the outer hemilaryngeal cartilage with the underlying laryngeal adductor muscle. The defects were repaired with muscle stem cell-derived muscle-PCL constructs (5 animals), myotube-derived muscle-PCL constructs (5 animals), motor end plate-expressing muscle-PCL constructs (5 animals), or PCL alone (controls; 5 animals). The outcome measures at 1 month included animal survival, muscle thickness, and innervation status as determined by electromyography and immunohistochemistry. RESULTS: All of the animals survived the 1-month implant period and had appropriate weight gain. The group that received motor end plate-expressing muscle-PCL constructs demonstrated the greatest muscle thickness and the strongest innervation, according to electromyographic activity and the percentage of motor end plates that had nerve contact. CONCLUSIONS: Although all of the tissue-engineered constructs provided effective reconstruction, those that expressed motor end plates before implantation yielded muscle that was more strongly innervated and viable. This finding suggests that this novel approach may be useful in the development of a tissue-engineered laryngeal replacement.Item Use of autologous adipose-derived mesenchymal stem cells for creation of laryngeal cartilage(Wiley, 2018-04) Zhang, Hongji; Voytik-Harbin, Sherry; Brookes, Sarah; Zhang, Lujuan; Wallace, Joseph; Parker, Noah; Halum, Stacey; Biomedical Engineering, School of Engineering and TechnologyOBJECTIVES/HYPOTHESIS: Adipose-derived mesenchymal stem cells (ASCs) are an exciting potential cell source for tissue engineering because cells can be derived from the simple excision of autologous fat. This study introduces a novel approach for tissue-engineering cartilage from ASCs and a customized collagen oligomer solution, and demonstrates that the resultant cartilage can be used for laryngeal cartilage reconstruction in an animal model. STUDY DESIGN: Basic science experimental design. METHODS: ASCs were isolated from F344 rats, seeded in a customized collagen matrix, and cultured in chondrogenic differentiation medium for 1, 2, and 4 weeks until demonstrating cartilage-like characteristics in vitro. Large laryngeal cartilage defects were created in the F344 rat model, with the engineered cartilage used to replace the cartilage defects, and the rats followed for 1 to 3 months. Staining examined cellular morphology and cartilage-specific features. RESULTS: In vitro histological staining revealed rounded chondrocyte-appearing cells evenly residing throughout the customized collagen scaffold, with positive staining for cartilage-specific markers. The cartilage was used to successfully repair large cartilaginous defects in the rat model, with excellent functional results. CONCLUSIONS: This study is the first study to demonstrate, in an animal model, that ASCs cultured in a unique form of collagen oligomer can create functional cartilage-like grafts that can be successfully used for partial laryngeal cartilage replacement.