颜面部注射美容材料应用现状与研究进展

2019-04-15 01:59秦雷邵月
中国美容医学 2019年4期

秦雷 邵月

[摘要]注射美容自一百多年前诞生以来,其材料和技术经历了极大的变革,目前颜面部注射材料主要是神经调节剂类及填充类,常用于面部年轻化、改善面部轮廓及矫正面部缺陷等,具有私密性佳、耗时短、起效快、创伤小及恢复快等优点,但注射美容相关的不良反应及并发症同时也在不断发生,影响治疗体验及最终效果,给就医者的身体、心理造成不同程度的伤害,严重时还对其生命安全造成威胁。本文就肉毒毒素及填充注射两方面在颜面部注射美容的临床进展进行综述,并展望注射美容未来的发展方向。

[关键词]注射美容;肉毒毒素;颜面部;透明质酸;自体脂肪

[中图分类号]R622   [文献标志码]A    [文章编号]1008-6455(2019)04-0169-05

Abstract: The history of cosmetic injection has been over one hundred years,great progress has been made in both materials and technology.The current materials are mainly botulinum toxin and fillers those have many advantages such as good privacy,time-consuming short, rapid onset, less invasive,faster recovery,and often used to rejuvenate the face,improve facial contour and correct facial defects,etc.However,at the same time,the adverse reactions and complications of cosmetic injection not only affect the experience of treatment and the final therapeutic effect,but also cause various degrees of injuries to beauty seekers both in physical and mental.In special cases,they may also threaten the security of life.This paper reviews the clinical progress of botulinum toxin injection and filling injection,and also makes a preliminary outlook on the future direction of injection cosmetic.

Key words: cosmetic injection; botulinum toxin; face; hyaluronic acid; autologous fat

注射美容的历史可从1899年的石蜡注射算起,至今已超百年。如今注射美容已得到了社会的高度认可,应用十分广泛,是整形美容外科不可或缺的部分,其材料及技术经过不断发展完善,已逐渐成熟、规范。目前,颜面部常用的注射材料一般分为两类[1]:神经调节剂类及填充类,前者常指肉毒毒素,后者以透明质酸及自体脂肪为主,还包括羟基磷灰石、聚乳酸等。

1  神经调节剂类

颜面部神经调节剂类注射材料,通常指的是肉毒毒素。肉毒毒素(botulinum toxin,BT),又称肉毒杆菌毒素,是肉毒梭状芽胞杆菌产生的神经毒素蛋白,共有8型,医美领域常用A型肉毒毒素(botulinum toxin type A,BTA),BTA的作用机制可归纳为[2-7]:①与突触前神经元细胞表面受体结合;②结合后的复合体内吞进入神经细胞;③断开二硫键,裂解突触相关蛋白;④L链进入细胞基质后切割底物蛋白,抑制乙酰胆碱释放。BTA抑制乙酰胆碱释放,却并不抑制其合成,3~6个月后新的神经-肌肉连接出现,肌肉收缩功能又能恢复。

BTA常用于除皱,特别是面部上1/3动态皱纹[8],如额纹、眉间纹及鱼尾纹等,目前对中下面部皱纹也有较多应用,均取得良好效果,就医者满意度也普遍较高[9]。有研究建议,注射BTA后应避免长时间紫外线照射,涂上SPE 30+的防晒霜,可获得更佳的美容效果[10]。BTA也用来改善咬肌肥大[11-12],是良性咬肌肥大患者瘦脸的首选方案。BTA还能治疗斜视、睑痉挛、面肌痉挛,对高低眉、唇外翻、嘴角歪斜、露龈笑、面部不对称等进行调整,对瘢痕也有治疗效果,能在一定程度上抑制伤口愈合期间瘢痕的形成[1]。但也有研究[13]认为BTA治疗瘢痕的实际效果可能很有限,需进一步研究明确争议。最近有报道BTA治疗难治性泪道引流障碍[14]的疗效显著,但当前实践经验太少,具体应用标准尚需进一步评估。还有报道[15]阐述了BTA辅助治疗口吃的可能性,期待BTA成为口吃多学科疗法的一部分。

BTA优点众多,如创伤小、起效快、无痕迹和总体安全性高等[8],但作为一种神经毒素,其副作用是不能被忽视的,注射BTA后,偶有过敏、复视、眼干、眼睑下垂、表情不自然、张口困难等不适,但基本都是暂时或可逆的,一般不会长期存在并影响最终的美容效果[16-17]。近年来,偶有报道肉瘤样肉芽肿[18]、假性动脉瘤[19]等较严重的并发症,有进一步分析、研究原因的价值。偶尔还会出现注射BTA后无反应的情况,其原因尚不清楚,可能是个体免疫系统存在差异,如存在毒素抗体等[17]。

2  填充注射类

自2003年FDA批准透明质酸填充剂应用于临床后,因其可降解、可酶解、无抗原性等优点,迅速获得了医美业界的青睐,现在是仅次于肉毒毒素的第二大注射美容產品。而羟基磷灰石类、聚乳酸类、富血小板血浆、聚甲基丙烯酸甲酯等填充剂也已逐步应用于临床,均取得不俗的成绩,一些新型填充剂仍在不断研发,如提取于鲑鱼生殖细胞的多聚核苷酸[20]、人体自身皮肤的成纤维细胞等[21]。目前,国内经CFDA批准的填充剂还较少,故而临床把填充剂的原料选择转向了自体组织和细胞,特别是自体脂肪及衍生物,具有取材和移植容易、无免疫反应等优点,受到很多就医者的喜爱,有取代透明质酸成为第一大注射填充材料的趋势。

2.1 透明质酸:透明质酸(hyaluronic acid,HA)即玻尿酸,属人体自身天然成分,本质是二糖单体(氨基葡萄糖及葡萄糖醛酸)经聚合形成的酸性黏多糖,作用是稳定细胞外基质。HA吸水能力很强,可锁住水分并保持皮肤弹性,具备较稳定的结构刚度[22]、适宜的生物相容性和可降解性,基本没有抗原特异性。Wollina等推测HA的机制[23]:①刺激成纤维细胞产生胶原;②结合水、刺激脂肪组织反应;③支撑并激活脂肪干细胞。最新研究[24]发现注射后的HA在皮肤中均匀分布,保持着纤维小梁网络结构,能在脂肪小叶间移动,且没有破坏原本完整的皮下结构及耐受性。

HA在颜面部常用于容量填充,填充颞部、隆鼻、丰唇等,还用于填充凹陷或瘢痕、矫正不对称、改善软组织萎缩等[25],效果均较好,一定程度上改善了五官比例,降低了开放手术及安置假体的风险。近来HA还被用来提升效果[26],即全面部多通道皮内微量注射,修饰细小皱纹和凹陷,改善肤质并恢复皮肤厚度,刺激胶原增生,达到年轻化的目的。

HA总体安全性高,但不良反应及并发症仍时有发生,如局部红、肿、痛,局部血肿、感染,迟发性纤维化、皮下结节、肉芽组织形成等,发生几率虽不高,可一旦发生对就医者心理和身体的伤害却是不能忽视的,处理不当还可能产生医疗纠纷。综合分析原因后,考虑一部分可能与HA纯度有关[27],也有部分是操作技术问题[28]。

不常见却严重的并发症如失明、皮肤组织坏死甚至脑梗死等则更需引起重视。血管栓塞导致视力障碍的病例并不少,国外的Beleznay[29]发现了98例,国内李小静[30]则总结了89例,Carruthers等[31]很多学者均认为填充注射导致的失明是不可逆的,Giselle等[32]虽提出过预判栓塞的办法,但仍缺乏绝对安全的避免手段。Goodman[33]曾报道1例HA致右眼部分失明的患者,短时间内连续两次(一次血管内,一次血管周围)注射透明质酸酶后视力恢复,可惜的是不能准确判断之前的失明诊断是否误诊(没有眼底照片等直接证据),他们继而认为血管周围注射的透明质酸酶能轻易穿过血管壁溶解HA,而这与Wang[34]的想法一致。HA导致的组织坏死常表现为术区皮肤发烫、毛细血管充盈不良、急性肌肉疼痛等[1],若未及时发现并处理将快速进展至皮肤青斑、溃疡甚至全层坏死,所以快速诊断即将发生的皮肤坏死十分重要,一经诊断应立即大剂量脉冲注射透明质酸酶,可取得良好效果[35-37]。HA致脑梗死的病例较少,Carle[38]等有所报道,治疗上以预防为主,没有比较系统有效的治疗方案,还容易恶化,造成偏瘫甚至死亡等严重后果。

2.2 自体脂肪:自体脂肪移植(autologous fat transfer,AFT)历史悠久,可追溯到1893年Neuber用其填充皮肤软组织凹陷。近年来,随着自体脂肪(autologous fat,AF)的获取及后续处理技术取得的巨大进步,其使用量大幅上升,在填充剂方面仅次于透明质酸。

AFT的颜面部应用与HA类似,但更佳的生物相容性、无过敏反应及肉芽肿风险等优势[39]使其发展很迅猛,而混合部分AF细胞和细胞外基质的自体乳糜脂在增生性瘢痕等瘢痕相关治疗中取得了良好效果[40],也值得进一步关注。然而移植后脂肪细胞成活率不稳定及不可预测成为制约AFT进一步发展的障碍,所以,近年来如何提高并稳定细胞移植后的成活率成了研究热点,研究者们从脂肪获取、处理及注射等环节切入,提出了脂肪干细胞(adipose-derived stem cells,ADSCs)[41]、细胞辅助脂肪移植(cell-assisted lipotransfer,CAL)[42]、Brava辅助细胞移植[43]、3L3M[44]、FAMI[45]等技术或理念,加之Rohrich等[46-48]对面部脂肪解剖结构的深入研究,似乎已提高了脂肪细胞移植后的成活率,并获得了就医者较高的满意度[49],然而一项纳入3 073份病例、平均随访时间13.9个月的Meta分析[50]报道了不同个体间AF体积保持量存在巨大差异(成活率不稳定且不可预知),故而在AF被称作真正的永久填充剂之前,应当首先评估其在生物相容性更佳的下一代填充剂出现后还是否合格,再进一步研究如何实现较高、较稳定成活率及长期保持的问题。

AFT的不良反应及并发症也与HA类似,轻微的如局部红、肿、痛,严重的如血管栓塞致失明、组织坏死等,但脂肪颗粒较HA直径更大且不一,因而更易栓塞大直径血管[51],如眼动脉、颅内动脉等。AFT特有的并发症是因脂肪坏死形成的油脂囊肿、钙化及瘢痕,较多数量的细胞坏死会取代胶原基质而形成瘢痕,瘢痕内小油脂囊肿又易导致慢性炎症反复发生,最终形成大量钙化灶,持续时间可达5年[52],此类囊肿经微创联合治疗[53]后在中期随访时取得良好效果,但仍需随访长期疗效。

2.3 其他材料:左旋聚乳酸(poly-L-lactic acid,PLLA)是少数被FDA批准的一类安全、填充效果极佳的降解型人工合成生物材料。具有良好生物相容性、低毒性、易于改性等优点[54-55],通过刺激成纤维细胞分泌胶原达到美容填充的目的[56],注射后需规律按摩,防止结节形成[1]。过去PLLA的问题是作为强疏水性物质,对细胞黏附力较差且降解物为乳酸,注射初期易引起轻微炎症反应,容易出现丘疹、结节。研究者们通过改良技术细节并严密随访,发现丘疹、结节发生率已明显降低[56-57],故而PLLA的未来前景应该会很好。

羥基磷灰石钙(calcium hydroxyapatite,CaHA)是高度交错聚合的高分子磷酸钙聚合物,广泛存在于人体骨组织[58],除高分子填充剂共有的优良生物相容性外,还具有注射后短期内可手工塑形的优势,在美国的填充剂使用量长期处于第二位,仅次于透明质酸。CaHA常用于较深层组织填充,如鼻唇沟填充、隆鼻等,在与HA的对照研究中取得了类似的效果及满意度[59],应用前景值得期待。

富血小板血浆(platelet rich plasma,PRP)是体外离心全血得到的高度浓缩自体血浆[60],含大量血小板,激活血小板可释放大量生长因子,包括血小板源性生长因子、血管内皮生长因子、成纤维细胞生长因子等[61],具有调节细胞增殖和分化、促进血管增生及炎性趋化等作用[62]。目前常联合其他方法如AFT,促进移植脂肪的血管化,提高成活率;还能联合激光应用于皮肤年轻化,可取得更佳的疗效[63];PRP单独使用可改善眼周皱纹、凹陷及黑眼圈,增加局部组织弹性[64]。在下一步研究中应量化PRP的最低需求量,以期治疗过程中获得更好的舒适感。

聚甲基丙烯酸甲酯(poly-methyl methacrylate,PMMA)是一种永久性不可生物降解材料,早期因部分医生担心存在延迟性、顽固性肉芽肿的风险而不愿使用,所以PMMA的发展比较缓慢[65]。而随着制造工艺改进,PMMA微球表面已非常光滑,显著降低了免疫诱导、细菌定植和肉芽肿形成的风险,一项随访时间超过5年、样本量超过1 000例的研究证实了这个结论[66]。故而在未来PMMA应该会迅速跟上甚至赶超传统填充剂。

3  不足及展望

目前国内面部注射美容发展迅速,各注射材料均因各自优势占据了一席之地,随着更多新材料获得审批而逐步进入临床,原本BTA、HA及AF三足鼎立的格局或将被打破。过去我们常常把目光放在各注射材料更广泛的应用上,对材料本身及并发症的研究往往缺乏足够重视,未来应该进行更多前瞻性基础研究及大样本回顾性临床研究,将材料本身及并发症的机制问题了解清楚,减少并发症特别是严重并发症的发生,为广大就医者提供一个更安全的注射美容环境。

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[收稿日期]2018-10-31