{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:05:17Z","timestamp":1781730317112,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>To develop an effective rabbit model of in vitro\u2010 and in vivo\u2010derived tissue\u2010engineered cartilage for laryngotracheal reconstruction (LTR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>1) Determination of the optimal scaffold 1% hyaluronic acid (HA), 2% HA, and polyglycolic acid (PGA) and in vitro culture time course using a pilot study of 4 by 4\u2010mm in vitro\u2010derived constructs analyzed on a static culture versus zero\u2010gravity bioreactor for 4, 8, and 12 weeks, with determination of compressive modulus and histology as outcome measures.<\/jats:p><jats:p>2) Three\u2010stage survival rabbit experiment utilizing autologous auricular chondrocytes seeded in scaffolds, either 1% HA or PGA. The constructs were cultured for the determined in vitro time period and then cultured in vivo for 12 weeks. Fifteen LTRs were performed using HA cartilage constructs, and one was performed with a PGA construct. All remaining specimens and the final reconstructed larynx underwent mechanical testing, histology, and glycosaminoglycan (GAG) content determination, and then were compared to cricoid control specimens (n = 13) and control LTR using autologous thyroid cartilage (n = 18).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>1) One rabbit underwent an auricular punch biopsy, and its chondrocytes were isolated and expanded and then encapsulated in eight 4 by 4\u2010mm discs of 1% HA, 2% HA, PGA either in rotary bioreactor or static culture for 4, 8, and 12 weeks, respectively, with determination of compressive modulus, GAG content, and histology.<\/jats:p><jats:p>2) Sixteen rabbits underwent ear punch biopsy; chondrocytes were isolated and expanded. The cells were seeded in 13 by 5 by 2.25\u2010mm UV photopolymerized 1% HA (w\/w) or calcium alginate encapsulated synthetic PGA (13 \u00d7 5 \u00d7 2 mm); the constructs were then incubated in vitro for 12 weeks (the optimal time period determined above in paragraph 1) on a shaker. One HA and one PGA construct from each animal was tested mechanically and histologically, and the remaining eight (4 HA and 4 PGA) were implanted in the neck. After 12 weeks in vivo, the most optimal\u2010appearing HA construct was used as a graft for LTR in 15 rabbits and PGA in one rabbit. The seven remaining specimens underwent hematoxylin and eosin, Safranin O, GAG content determination, and flexural modulus testing. At 12 weeks postoperative, the animals were euthanized and underwent endoscopy. The larynges underwent mechanical and histological testing. All animals that died underwent postmortem examination, including gross and microhistological analysis of the reconstructed airway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirteen of the 15 rabbits that underwent LTR with HA in vitro\u2010 and in vivo\u2010derived tissue\u2010engineered cartilage constructs survived. The 1% HA specimens had the highest modulus and GAG after 12 weeks in vitro. The HA constructs became well integrated in the airway, supported respiration for the 12 weeks, and were histologically and mechanically similar to autologous cartilage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The engineering of in vitro\u2010 and in vivo\u2010derived cartilage with HA is a novel approach for laryngotracheal reconstruction. The data suggests that the in vitro\u2010 and in vivo\u2010derived tissue\u2010engineered approaches may offer a promising alternative to current strategies used in pediatric airway reconstruction, as well as other head and neck applications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA. <jats:italic>Laryngoscope<\/jats:italic>, 126:S5\u2013S21, 2016<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.25676","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T13:40:01Z","timestamp":1444916401000},"source":"Crossref","is-referenced-by-count":21,"title":["Pediatric laryngotracheal reconstruction with tissue\u2010engineered cartilage in a rabbit model"],"prefix":"10.1002","volume":"126","author":[{"given":"Ian N.","family":"Jacobs","sequence":"first","affiliation":[{"name":"Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Redden","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Goldberg","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hast","sequence":"additional","affiliation":[{"name":"School of Engineering and Applied Sciences at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Salowe","sequence":"additional","affiliation":[{"name":"School of Engineering and Applied Sciences at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Mauck","sequence":"additional","affiliation":[{"name":"School of Engineering and Applied Sciences at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Doolin","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.1991.101.s56.1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940111001204"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2008.11.035"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348949910800613"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8493529"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.429656"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.05.033"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2012.03.006"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v019a08"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1115\/1.1318906"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1114\/1.1512676"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099987"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.0256"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2006.20.2932"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.130.9.1048"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLG.0b013e31811434ae"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20750"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.2741\/3853"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.2741\/3687"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/jpsu.2002.33837"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.08.073"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/am403966x"},{"key":"e_1_2_7_24_1","unstructured":"MauckR.Penn Center for Musculoskeletal Disorders Biomechanics Core. 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