《柳叶刀》：首次利用人工软骨成功实现鼻再造术

　　

生物通报道：瑞士巴塞尔大学的科学家，首次利用实验室中生长的软骨成功实现鼻再造手术。研究人员从患者的鼻中隔提取软骨细胞，将其增殖与扩展到一片胶原膜上。然后，根据缺陷对这个人工软骨进行塑型并植入。相关研究结果发表在2014年4月11日的英国著名医学杂志《柳叶刀》（The Lancet）。

来自瑞士伯尔尼大学的研究小组报道称，可以利用人工设计软骨用于鼻再造术。他们使用一种称为组织工程学的方法，从患者自己的细胞发展软骨组织。这项新技术已经应用于5位患者中，他们年龄在76到80岁之间，在皮肤癌手术后鼻子具有严重的缺陷。鼻再造术一年后，这5名患者对他们的呼吸能力，以及鼻子的造型都感到非常满意。他们都没有出现任何副作用。

来自鼻中隔的细胞
这项研究中的非黑素瘤皮肤癌，在鼻子中是最常见的，特别是鼻子的鼻翼部位，因为它累积暴露于阳光下。为了完全切除肿瘤，外科医生经常也需要切掉部分软骨。一般地，医生会从鼻中隔、耳朵或肋骨提取再造移植物，用于功能性鼻再造术。然而，因为需要额外的手术，这个过程非常具有侵入性，患者非常痛苦，并可导致切除部位的并发症。

目前，伯尔尼大学生物医学系的研究小组与巴塞尔大学医院的同事合作，开发出一种替代方法，利用患者鼻中隔细胞成长起来的人工软骨组织。他们提取出一小块活检组织，分离软骨细胞（chondrocytes）并繁殖它们。扩展后的细胞被接种到胶原膜上培养2周，产生的软骨是原来活检组织大小的40倍。然后，根据鼻孔的缺陷将人工移植物塑型并植入。

面容重建的可能性
根据巴塞尔大学医院生物医学系的组织工程学教授Ivan Martin介绍：“这种人工软骨的临床结果可与当前的标准手术相比。这项新技术可帮助身体更好地接受新组织，并提高鼻孔的稳定性和功能。该方法为使用人工软骨用于更具挑战性的面部重建手术（如完整的鼻子、眼睑或耳朵）开辟了道路。”

目前，另一项膝关节软骨修复研究正在检测同样的人工移植物。尽管前景比较乐观，但距离这些程序应用于临床实践仍然还相当遥远。Martin说：“我们需要在更大的患者组群中进行严格的功效评估，并发展保证经济效益的商业模式和制造模式。”（生物通：王英）

延伸阅读：Science：国际团队利用钓鱼线研制出强大人工肌肉

生物通推荐原文摘要：
Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial
Summary
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.