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肿瘤切除后用于鼻重建的工程化自体软骨组织:首例人体观察性试验。

Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial.

机构信息

Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.

Department of Surgery and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.

出版信息

Lancet. 2014 Jul 26;384(9940):337-46. doi: 10.1016/S0140-6736(14)60544-4. Epub 2014 Apr 10.

DOI:10.1016/S0140-6736(14)60544-4
PMID:24726477
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).

FINDINGS

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.

INTERPRETATION

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.

FUNDING

Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.

摘要

背景

自体鼻中隔、耳或肋软骨是切除非黑素瘤皮肤癌后双层切除鼻翼小叶的外科重建的标准材料。我们评估了工程化自体软骨移植物是否允许安全且功能性地重建鼻翼小叶。

方法

在巴塞尔大学医院(瑞士巴塞尔)进行的首次人体试验中,我们招募了五名患者。入选标准为:年龄至少 18 岁,且鼻翼小叶切除非黑素瘤皮肤癌后出现双层缺损(鼻翼亚单位面积≥50%)。软骨细胞(从局部麻醉下收集肿瘤活检样本时从鼻中隔采集的 6mm 软骨活检样本中分离出来)在自体血清中进行扩增、接种和培养,在胶原 I 和胶原 III 膜上培养 4 周。所得工程化软骨移植物(25mm×25mm×2mm)在肿瘤切除后,通过正中额部或鼻唇沟皮瓣进行术中塑形和植入,如用自体软骨进行标准重建。6 个月后皮瓣精细修整时,我们采集修复组织活检样本并进行组织学分析。主要终点是术后 12 个月重建时的安全性和可行性。植入后至少 1 年,当重建通常稳定时,我们评估患者满意度和功能结果(鼻翼皮肤感觉、结构稳定性和呼吸流速)。

结果

2010 年 12 月 13 日至 2012 年 2 月 6 日,我们招募了 2 名女性和 3 名年龄 76-88 岁的男性。所有工程化移植物均包含透明软骨和纤维软骨混合基质。植入后 6 个月,重建组织显示出典型的鼻翼小叶纤维肌性脂肪结构。1 年后,所有患者对美学和功能结果均满意,且未记录到不良事件。重建区域的皮肤感觉和结构稳定性均在临床上令人满意,呼吸功能正常。

解释

自体鼻中隔软骨组织可被工程化并临床用于鼻翼小叶的功能重建。现在应评估工程化软骨在其他具有挑战性的面部重建中的应用。

资金来源

巴塞尔大学医院外科系基金会;和巴塞尔两地的克劳斯·利加基金会。

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