title: Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial.
abstract: BACKGROUND
  Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration.
  
  
  METHODS
  In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate).
  
  
  RESULTS
  Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function.
  
  
  CONCLUSIONS
  Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions.
  
  
  BACKGROUND
  Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Ilario
authors.initials: I
authors.lastname: Fulco
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Miot
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. Electronic address: martin.haug@usb.ch.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Haug
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barbero
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Anke
authors.initials: A
authors.lastname: Wixmerten
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Feliciano
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Francine
authors.initials: F
authors.lastname: Wolf
authors.affiliation: Institute of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Gernot
authors.initials: G
authors.lastname: Jundt
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Marsano
authors.affiliation: Department of Plastic Surgery, Guy's and St Thomas' Hospital, London, UK.
authors.forename: Jian
authors.initials: J
authors.lastname: Farhadi
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Jakob
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Schaefer
authors.affiliation: Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. Electronic address: ivan.martin@usb.ch.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019902:Chondrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055171:Nasal Cartilages / Q000601:surgery*; D009669:Nose Neoplasms / Q000601:surgery*; D019651:Plastic Surgery Procedures / Q000379:methods; D012878:Skin Neoplasms / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods*