Application and advances of nanozyme-loaded tissue engineering scaffolds in wound repair
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摘要: 有效重建受损皮肤组织并恢复其完整性和功能性仍是当前创伤修复领域面临的重要医学问题。近年来,纳米酶和组织工程支架在再生医学领域的飞速发展,使得开发新型皮肤创伤修复材料成为可能。该综述立足于皮肤创伤修复与再生过程,简述了纳米酶及其催化机制,同时介绍了常见的负载纳米酶的组织工程支架及其制造策略,总结了负载纳米酶的组织工程支架在创面修复过程中抗菌、抗炎等阶段的应用并探讨了其未来发展方向。Abstract: At present, effective reconstruction of the integrity and functionality of damaged skin tissue remains an important medical problem in the field of wound repair. In recent years, the rapid development of nanozymes and tissue engineering scaffolds in the field of regenerative medicine has made it possible to develop new skin wound repair materials. Based on the process of skin wound repair and regeneration, this review briefly describes the nanozymes and its catalytic mechanism. At the same time, the common tissue engineering scaffolds loaded with nanozymes and their manufacturing strategies are introduced, the application of tissue engineering scaffolds loaded with nanozymes during the stages of anti-bacteria and anti-inflammation in the process of wound repair is summarized, and their future development direction is discussed.
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Key words:
- Biocompatible materials /
- Tissue engineering /
- Stents /
- Nanozymes /
- Wound repair /
- Skin regeneration
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(1)详述了游离颞浅筋膜瓣/股前外侧筋膜瓣的切取层次和获取经验,具有临床参考价值。
(2)针对游离筋膜瓣术后血运观察困难等问题,提出了多种新颖且实用的应对方法,具有启发意义。
手足、胫前、踝后区等部位皮下软组织菲薄,在遭遇烧创伤时极易造成肌腱、血管及骨质的外露,若修复不佳,会对患者的感觉与运动功能以及外观产生严重影响 [ 1] 。对于上述区域内较小的组织缺损,利用创面周围的局部皮瓣或岛状皮瓣修复,效果较好;但对于较大的深度组织缺损,临床上常采用游离皮瓣等进行修复。对于手指、足趾、踝后、胫前、足背等特殊部位的创面而言,即使采用穿支皮瓣修复并对皮瓣上的脂肪进行大量修剪,术后外观仍然较臃肿,后期常需行多次去脂塑形手术,给患者造成沉重负担 [ 2] 。随着临床医学发展和外科技术革新,利用筋膜组织制备筋膜瓣,为此类创面的修复带来了新选择。10余年来,本团队对手足、胫前和踝后区域的复杂深度组织缺损创面,采用游离颞浅筋膜瓣/股前外侧筋膜瓣结合刃厚皮片移植的方法进行修复,取得了较佳效果 [ 3, 4, 5, 6, 7] 。
1. 游离颞浅筋膜瓣/股前外侧筋膜瓣的解剖和手术方法
筋膜组织是人体重要的结缔组织,位于皮肤与肌肉之间,主要由皮下疏松结缔组织构成的浅筋膜和浅筋膜深层致密结缔组织构成的深筋膜组成。浅筋膜内主要包含脂肪、浅血管、淋巴和皮神经等组织 [ 8] 。而在深筋膜的深、浅面,穿动脉、皮下动脉和筋膜下动脉主干及分支交互吻合,形成了四通八达的血管网,为筋膜组织提供了丰富的血供。3个动脉系统中的1个动脉系统血供被中断不会影响筋膜组织的总体血供,这是利用筋膜组织制备筋膜瓣应用于临床的重要解剖学基础 [ 9, 10] 。
1.1 颞浅筋膜瓣的解剖和切取
颞浅筋膜也被称为颞顶筋膜,在颞区位于头皮和皮下组织之下,其深面由浅至深依次为含微血管的疏松结缔组织间隙、颞深筋膜、颞肌和颅骨外膜 [ 11] 。颞浅筋膜前与额肌、眼轮匝肌相连,后与枕肌、耳后肌相连,上与颅顶帽状腱膜相延续,上达颅顶、下至颧弓。颞浅筋膜在顶区与头皮连接紧密,不易分开;在颞区则较易与皮肤解剖游离开。在颞浅筋膜深面,因疏松结缔组织间隙的存在使颞浅筋膜易与颞深筋膜解剖分离。颞浅筋膜主要由走行于其内的颞浅动脉及其终末分支额支和顶支供血。颞浅动脉自颈外动脉发出后,于外耳道软骨和颞下颌关节囊之间的浅筋膜浅出,行至颧弓上约2 cm处以约60°夹角分出额支和顶支,沿途发出许多分支形成动脉吻合网。颞浅静脉多数走行于颞浅动脉浅面后方,末端注入下颌后静脉,但其变异较多,回流常不恒定 [ 12, 13] 。
切取颞浅筋膜瓣术前可使用多普勒超声血流探测仪测定颞浅动脉走行并标记。于耳屏前上方沿颞浅动脉走行向颞顶部做纵行切口,显露颞浅动静脉后向颞顶部延长切口。根据所需修复创面大小,可在颞顶部将切口末端设计为“T”形或“Y”形,以便显露分离颞浅筋膜。颞浅筋膜瓣切取层次浅面为毛囊下层,深面为颞深筋膜上层。颞浅筋膜深面与颞深筋膜存在疏松结缔组织间隙,切取时较易分离。在明确颞浅筋膜的大小及层次后,可从其上缘切开向下逆行切取,分离形成含有颞浅动静脉的筋膜瓣 [ 14] 。
1.2 股前外侧筋膜瓣的解剖和切取
股前外侧皮瓣现已被广泛应用于临床,其主要供血动脉为旋股外侧动脉降支及其穿支血管。股前外侧筋膜瓣相较于股前外侧皮瓣少切取了皮肤和皮下组织,保留了旋股外侧动静脉降支及其穿支血管、阔筋膜和部分浅筋膜。旋股外侧动脉降支在股外侧肌和股中间肌之间向下走行,通常在以髂髌线中点为中心、半径约5 cm的圆的外下象限内发出大的股外侧肌皮穿支或肌间隙皮支。旋股外侧动脉降支第1肌皮穿支最为粗大,通常作为股前外侧皮瓣及筋膜瓣的供血血管。旋股外侧动脉降支多数有2条伴行静脉,且所有的肌皮动脉穿支都有伴行静脉,多数为1条 [ 15] 。
股前外侧筋膜瓣的血管主要为层状分布,在各层中轴形血管分布由浅入深,长度逐渐变短,最终形成真皮下血管网,轴形血管和真皮下血管网组合构成典型的树枝状三维结构 [ 16] 。因此术中可以大胆地由浅面向深面剔除筋膜瓣多余的脂肪,而不影响筋膜瓣的血运。由此可以确定股前外侧筋膜瓣深面切取层次为阔筋膜下,并可根据创面需求携带部分肌肉。浅面切取层次最上层可达真皮下血管网下层,由此获取的即为股前外侧脂肪筋膜瓣;浅面切取层次最下层为阔筋膜上层,由此获取的即为阔筋膜瓣 [ 17] 。临床上在应用股前外侧筋膜瓣时,可根据待修复创面缺损组织量决定筋膜瓣切取层次。股前外侧筋膜瓣切取前可先使用多普勒超声血流探测仪确定旋股外侧动脉降支穿支血管的浅出点,根据浅出点位置及受区缺损大小设计筋膜瓣切取范围。设计“T”形或“S”形切口切开皮肤后,于术前确定好的切取层次向周围分离皮肤及皮下组织至设计边缘,此后于设计的筋膜瓣外缘、上下缘向深部切取直至阔筋膜深面。掀起阔筋膜探查,确保旋股外侧动脉降支的肌皮穿支或肌间隙皮支进入筋膜瓣后,再切开筋膜瓣的内侧缘。此后沿筋膜瓣供血血管走行向近端解剖,直至显露旋股外侧动脉降支主干,分离周围组织形成含有旋股外侧动脉降支主干血管的筋膜瓣。
2. 游离筋膜瓣联合刃厚皮片的临床应用经验
2.1 游离筋膜瓣联合刃厚皮片移植的优点
筋膜瓣因其独特的解剖学和生理学特性,适用于部分特殊创面的修复。本团队采用游离筋膜瓣联合刃厚皮片移植的方法修复手指、足趾、手背、足背、踝后及胫前等皮下组织菲薄的区域,取得了良好的效果 [ 3, 4, 5, 6, 7] 。该修复方法具有以下独特的优势:(1)术后受区不臃肿,无须后期行去脂塑形手术。(2)筋膜瓣组织致密,在其表面植刃厚皮片罕见挛缩,外形美观。(3)对于肌腱外露的创面,因颞浅筋膜及阔筋膜深面含有大量的透明质酸,使用筋膜瓣覆盖创面更加符合组织学需求,在利于肌腱滑动的同时,可有效防止肌腱与周围组织粘连,有助于患者手足功能的康复。本团队采用股前外侧筋膜瓣(面积约9 cm×5 cm)联合头部刃厚皮片移植修复1例患者(女,32岁)左足背皮肤坏死创面(面积约为8 cm×4 cm),术后筋膜瓣及所植皮片均存活良好,足背外表平整、不臃肿,足功能恢复良好( 图1)。(4)对于关节囊及跟腱缺损的创面,筋膜瓣可在裁剪或折叠后修复创面并加强关节囊及跟腱,满足关节囊及跟腱修复后的组织强度要求和功能学需求 [ 18] 。(5)颞浅筋膜瓣及股前外侧筋膜瓣具有完整的动静脉循环系统,可保证丰富的血供,且具备良好的抗感染能力,可有效促进存在骨髓炎的感染性创面的愈合。本团队采用股前外侧筋膜瓣(面积约17 cm×5 cm)联合头部刃厚皮片移植修复1例患者(男,42岁)右侧胫前溃疡伴胫骨外露创面(面积约15 cm×4 cm),术后筋膜瓣及所植皮片均存活良好,术区外观平整,骨髓炎治愈( 图2)。(6)筋膜瓣柔软且易裁剪塑形,用其填塞手足不规则腔隙性创面,不会造成组织肥厚而影响功能。(7)糖尿病足患者末梢血运通常较差,行游离筋膜瓣移植,采取端侧吻合血管的方式相当于为糖尿病足溃疡患者末梢构建了新的血运,更有利于创面的远期恢复。(8)筋膜瓣切取后的供区皮肤无张力可直接缝合,术后瘢痕增生不明显,尤其是颞部筋膜瓣切取后,头发生长后可遮蔽切口,符合美学要求。
2.2 游离筋膜瓣联合刃厚皮片移植的术中操作难点和注意事项
游离筋膜瓣联合刃厚皮片移植的方法在临床实践中除了覆盖面积有限、游离操作对术者的手术技能要求较高等不足外,还存在诸多难点和注意事项。
游离移植筋膜瓣的血运观察困难。既往有术者在筋膜瓣游离移植后行换药处理,待筋膜瓣表面形成致密红色肉芽组织后再行Ⅱ期植皮手术 [ 19, 20] 。该方式虽有助于观察筋膜瓣血运,但也因需要Ⅱ期手术延长了治疗周期,给患者带来了额外的生理和经济负担。此外,亦有术者在筋膜瓣切取时采取保留远端部分皮瓣,进行半筋膜瓣半皮瓣移植修复创面 [ 21] 。该方式理论上血运监测方便,但实际应用价值有限,因为筋膜瓣本身切取范围有限,如果携带皮瓣过小,则血运观察仍很困难,如携带皮瓣范围过大,则不可避免会造成受区臃肿,失去了筋膜瓣的意义。针对此问题,本团队的实践经验如下:(1)在筋膜瓣切取时留取较长的血管蒂,使血管蒂部吻合区域超出筋膜瓣及皮片覆盖范围,从而有利于在术后早期使用多普勒超声血流探测仪动态监测所吻合血管的血流动力学变化,进而判断是否存在血管危象;(2)筋膜瓣上所植皮片推荐采用较薄的刃厚皮片,术后打包包扎并留置观察孔,通过观察孔定期观察皮片及皮片下筋膜瓣的颜色来确定筋膜瓣的血运情况。
为达到筋膜瓣超薄化的效果,股前外侧筋膜瓣的切取层次虽然可达阔筋膜浅面,但本团队更推荐尽量保留筋膜瓣上厚3~5 mm的脂肪组织,因为在此层次切取时不易损伤旋股外侧动静脉降支血管的穿支,有利于筋膜瓣的血液循环。如不保留脂肪组织,仅需获取阔筋膜,切取时也应注意保护阔筋膜表面菲薄的疏松结缔组织,该层结缔组织中包含阔筋膜表面的血管网,探查可见清晰的呈星状分布的血管穿出点,过多损伤该层结缔组织会影响阔筋膜的血液循环。而对于大腿脂肪偏少的患者而言,切取股前外侧筋膜瓣时还需避免筋膜层切取过厚导致供区皮肤坏死。
股前外侧筋膜瓣切取时,若阔筋膜切取宽度≤5 cm,剩余阔筋膜多可直接拉拢缝合覆盖封闭下层肌肉;但若切取宽度>5 cm,剩余阔筋膜可能难以拉拢缝合,若强行缝合易导致骨-筋膜室综合征,但若不对阔筋膜进行处理而直接缝合皮肤软组织封闭供瓣区,则术后易出现肌疝。本团队在切取宽度>5 cm的阔筋膜时,常规采用人工补片修补阔筋膜,有效防止了术后肌疝的发生。
颞浅筋膜瓣切取时,因头皮与浅筋膜间存在众多垂直纤维纵隔,在颞部毛囊下层分离颞浅筋膜时存在困难。若解剖层次判断不清,切取过浅易损伤毛囊,导致术后脱发;切取过深则易损伤颞浅筋膜血管网,从而影响血运。本团队的经验为,若切取层次判断存在困难时,可先在术区注射肿胀液以利于组织分离;也可根据顶部帽状腱膜向下与颞浅筋膜相延续的解剖学基础,采取先在顶部皮下显露部分帽状腱膜,再沿帽状腱膜向颞部分离的方式明确切取层次。此外,为了减少术后头皮切口线区域的脱发,术者在切开头皮时需严格保持垂直入路,避免斜行切入导致毛囊过度受损。
3. 小结
游离筋膜瓣联合刃厚皮片移植除具有游离皮瓣血运好、抗感染能力强的优点外,还具有组织柔软、纤薄、易裁剪,供区皮肤可直接缝合,功能影响小,受区外形美观、不臃肿,术后利于功能康复等众多优势。尤其是在大面积烧伤患者供区匮乏的情况下,该方式可有效解决患者的修复难题,具有较大的临床应用价值。
所有作者均声明不存在利益冲突 -
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