gms | German Medical Science

Introduction: Skin cancer is the most prevalent reason for surgically creating a multilayer defect, consisting of skin and cartilage, of the alar lobule of the nose. Beside local flaps, autologous cartilage from nasal septum, ear or rib is the standard material for a solid reconstruction of the nasal alar lobule following two-layer excision. Following extensive in vitro and pre-clinical studies, we assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration, bypassing complications, limitations and morbidity of native cartilage harvest.

Material and methods: We performed a phase I, prospective, uncontrolled, investigator initiated clinical trial with the objective of demonstrating that engineered nasal cartilage grafts are suitable for use in reconstructive surgery of the nose. Five patients (76-88 years) with two-layer defects from non- melanoma skin cancer in the alar lobule accepted the novel procedure. Chondrocytes, isolated from a 6-mm punch of the nasal septum harvested under local anaesthesia during tumour biopsy, were expanded, seeded and cultured with autologous serum onto collagen type I/III membranes under Good Manufacturing Practices for a total of four weeks. The resulting engineered cartilage grafts (25x25x2mm) were shaped intra-operatively and implanted after tumour excision. Outer lining was reconstructed using different local or regional flaps as usual in the standard reconstruction procedure. After six months, during flap refinement, second look biopsies of repair tissues were harvested and histologically analysed. At least one year after implantation, when reconstruction is typically stabilized, patients were assessed for safety, aesthetic and functional outcomes. Monofilament and rhinomanometry tests were used to quantify alar cutaneous sensibility, mechanical stability and respiratory flow rate.

Results: All engineered grafts contained a mixed hyaline-fibrous cartilage matrix. Six months after implantation, reconstructed tissues displayed fibro-muscular-fatty structures typical of the alar lobule. After one year, all patients were satisfied with the aesthetic and functional outcome and no adverse events were recorded. The procedure resulted in sensibility and structural stability of the reconstructed area, with adequate respiratory function and no donor site morbidity.

Conclusion: Autologous nasal cartilage tissues can be engineered and clinically used to replace native cartilage grafts. The paradigm can be explored for more challenging reconstructions in facial surgery.