Research advances on multifunctional hydrogel dressings for treatment of diabetic chronic wounds
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摘要:
糖尿病会导致多种并发症如慢性创面(糖尿病足),是导致糖尿病患者死亡的重要原因之一。高血糖、高氧化应激水平、高炎症水平以及易感染等不利因素使糖尿病致慢性创面难以愈合,甚至进一步恶化。水凝胶材料由于具有含水量高、生物相容性好和理化性能可调控等优点,已成为当前创面敷料研究中的热点材料。相较于纱布等传统敷料,水凝胶敷料可为创面提供有利于愈合的湿润环境。通过负载活性物质和改变水凝胶组成及结构,水凝胶敷料可被赋予优异的组织黏附、抗菌、抗氧化以及调控炎症因子表达等功能,因此其在创面敷料应用领域中具有广阔的前景。本文基于糖尿病致慢性创面微环境和水凝胶材料的特点,总结了近年来用于治疗糖尿病致慢性创面的新型多功能水凝胶敷料的研究进展,同时探讨了当前水凝胶敷料的不足并提出展望。
Abstract:Diabetes can lead to a variety of complications, such as chronic wound (diabetic foot), which is one of the important causes of death for patients with diabetes. Unfavorable factors such as high blood glucose, high level of oxidative stress and inflammation, and susceptibility to infection lead to difficult healing and even worsening of diabetic chronic wounds. Due to the advantages of high water content, good biocompatibility, and tunable physicochemical properties, the hydrogels have become hot-spot materials in wound dressing research. Compared with the traditional dressings such as gauze, the hydrogel dressings can provide a moist environment that is beneficial for wound healing. By loading of bioactive components and modulation of compositions and structures of hydrogels, the hydrogel dressings can be endowed with excellent tissue adhesion, antibacterial ability, anti-oxidation, and inflammation regulation effect, etc., and thus show great prospects in wound dressing applications. Based on the characteristics of hydrogel materials and microenvironment of diabetic chronic wound, this review summarized the research advances on new multifunctional hydrogel dressings for the treatment of diabetic chronic wounds in recent years, and discussed the drawbacks of current hydrogel dressings with prospects proposed.
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Key words:
- Diabetic foot /
- Wound healing /
- Hydrogel /
- Inflammation /
- Dressing
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(1)应用足部相应位置的微型皮瓣游离移植修复手指Ⅳ度电烧伤创面,组织结构相似度高,功能相近,患指愈后外观自然。
(2)足部作为皮瓣供区,位置相对隐蔽,可供切取皮瓣面积相对较小,愈后无功能障碍。
(3)证实将足部游离微型皮瓣携带的感觉神经与患指损伤处的近端神经吻合之后,手指感觉恢复接近正常。
手指Ⅳ度电烧伤创面深达深筋膜以下,往往伴有肌腱和骨外露等,修复困难,通常需要应用皮瓣进行修复。随着显微外科技术及皮瓣解剖技术的不断发展,人们对创面修复有了更高的要求,更加注重功能的重建和外观的修复 [ 1] 。因此如何选择合适的皮瓣修复手指Ⅳ度电烧伤创面仍值得探讨。本研究中应用足部微型皮瓣游离移植Ⅰ期修复手指Ⅳ度电烧伤创面,取得了较好的临床效果。
1. 对象与方法
本回顾性观察性研究符合《赫尔辛基宣言》的基本原则。根据郑州市第一人民医院(以下简称本院)伦理委员会的相关规定,可以在不泄露患者信息的情况下对其有关临床资料进行分析研究。
1.1 入选标准
纳入标准:(1)性别、年龄不限;(2)确诊为手指Ⅳ度电烧伤但不伴指坏死者;(3)采用足部游离微型皮瓣修复者。排除标准:(1)术中或随访资料不完整者;(2)随访时间不足10个月者。
1.2 临床资料
2017年7月—2022年2月,本院收治20例符合入选标准的手指Ⅳ度电烧伤患者,其中男19例、女1例,年龄18~64岁,致伤电压为380 V~10 kV,均为单指受累。共20处创面,其中15处创面位于掌侧,包括拇指8处、示指5处、中指2处;5处创面位于背侧,包括示指1处、中指4处;原始创面的面积为3.0 cm×2.0 cm~6.0 cm×2.5 cm;其中肌腱、血管和/或神经外露创面15处,骨或关节外露创面5处。手术时间为伤后7~20 d。
1.3 手术方法
1.3.1 受区创面床准备
根据患者意愿,选择全身麻醉或者臂丛神经阻滞+腰硬联合麻醉。根据烧伤部位,对指掌侧创面清创后,探查指掌侧固有神经、血管及指深屈肌腱的损伤程度,保留轻度变性的肌腱,对缺损的指深屈肌腱应用患指近端指浅屈肌腱或掌长肌腱重建。解剖损伤严重的指固有血管至正常喷血,或者解剖至指总动脉处备用,解剖近端指掌侧固有神经至组织正常处备用。对指背侧创面清创后,探查伸指肌腱的损伤程度及关节完好程度,彻底清除坏死组织,保留轻度变性的肌腱和关节周围腱性组织,应用掌长肌腱修复患指伸指肌腱缺损部分。在鼻烟窝处解剖桡动脉末端及头静脉分支备用。最后测量创面面积,应用蓝布拓模,用以设计切取皮瓣。本组患者清创后创面面积为4.5 cm×2.0 cm~7.0 cm×3.0 cm。
1.3.2 皮瓣设计与切取
根据手指创面位置,遵循组织结构相似性原则,采用足底内侧皮瓣修复10处创面、采用拇趾腓侧皮瓣修复5处创面、采用足背动脉皮瓣修复5处创面。应用拓模分别在足底内侧、拇趾腓侧、足背设计皮瓣,切口边缘均在拓模外侧0.5 cm左右。所有皮瓣设计完成后,在血管蒂处设计三角瓣,用以覆盖吻合处血管,减轻吻合口处压力,避免卡压血管吻合口。
1.3.2 .1 足底内侧皮瓣
沿设计线切开皮瓣内外侧缘,在深筋膜深层锐性向皮瓣中心分离,注意保护进入皮瓣的血管穿支。在拇展肌与屈趾肌间隙内探寻足底内侧动脉浅支主干,由远及近游离皮瓣。在皮瓣近端沿胫后动脉走行向内踝下方做“Z”字形切口,于拇展肌起点以远1 cm处切断该肌,在拇展肌深面分离足底内侧动静脉及足底内侧神经,切断并结扎远端血管,并切取足够长度的血管、神经蒂,游离皮瓣准备移植。本组患者足底内侧皮瓣切取面积为7.0 cm×3.0 cm~8.0 cm×3.5 cm。
1.3.2 .2 拇趾腓侧皮瓣
以健侧拇趾趾掌侧固有动脉为皮瓣轴线,首先沿设计线切开皮瓣内侧缘,并沿拇趾腓侧向足背做“Z”字形切口,切开皮肤,在皮下筋膜层寻找合适的包含在皮瓣内的浅静脉。然后切开皮瓣外缘皮肤,向内侧分离至血管蒂处,分离出足够长度的拇趾趾掌侧固有动脉及其伴行神经,必要时在第1和第2跖骨间探查拇趾腓侧血管的来源。最后,切开皮瓣远端,在第1趾蹼处解剖并结扎通向第2趾的分支,保留足够长度的血管、神经,游离皮瓣准备移植。本组患者拇趾腓侧皮瓣切取面积为5.0 cm×2.5 cm~5.5 cm×3.0 cm。
1.3.2 .3 足背动脉皮瓣
在健侧足背按足背动脉走行对称设计皮瓣,切取平面为深筋膜深面。首先,切开皮瓣近侧缘皮肤,在浅筋膜层分离穿入皮瓣的大隐静脉,于皮瓣外侧在深筋膜层面锐性向皮瓣中心分离,探查足背动脉及其伴行静脉,同时注意保护趾长伸肌腱腱膜。然后,切断并结扎与足底深支动静脉血管交通支,由远及近分离皮瓣。最后,在留取合适长度的足背动静脉后,于血管近端离断血管蒂,游离皮瓣准备移植。本组患者足背动脉皮瓣切取面积为7.0 cm×3.5 cm~7.5 cm×3.5 cm。
1.3.3 皮瓣移植和供区处理
本组患者的皮瓣切取面积为5.0 cm×2.5 cm~8.0 cm×3.5 cm。将上述皮瓣断蒂后分别移植于相应手指受区。采用足底内侧皮瓣或者拇趾腓侧皮瓣修复指掌侧创面时,将皮瓣血管蒂动脉与患手指掌侧固有动脉或指掌侧总动脉近端端端吻合,将血管蒂静脉与患手指背静脉端端吻合,将皮瓣携带的神经与指掌侧固有神经近端外膜端端吻合,不桥接缺损的血管、神经。本组患者共15处创面与皮瓣行神经吻合。采用足背动脉皮瓣修复指背侧创面时,将皮瓣血管蒂动脉与患侧手背鼻烟窝处桡动脉末端端端吻合,血管蒂静脉与患侧手背鼻烟窝处头静脉分支端端吻合。最后,检查皮瓣确定血运良好后,将皮瓣与创缘间断缝合,采用无菌敷料包扎术区并留观察窗。皮瓣供区创面移植大腿中厚皮覆盖并加压固定。
1.4 术后处理
嘱患者绝对卧床10~14 d,将患肢抬高。采用红外线烤灯照射保温,观察皮瓣血运情况,常规行抗感染、抗痉挛、抗凝治疗。术后12~14 d视创面愈合情况拆线,并开始功能锻炼;行肌腱、神经修复者采用高分子夹板外固定3~4周后再开始功能锻炼。
1.5 观测指标
术后观察皮瓣和皮片成活情况。随访观察皮瓣外观以及患指末梢温度、颜色。于末次随访时,采用中华医学会手外科学会上肢部分功能评定试用标准 [ 2] 评估患指关节功能及皮瓣感觉恢复情况,测量吻合神经皮瓣处皮肤两点辨别觉距离;采用张浩等 [ 3] 制订的疗效满意度评分表(总分5~10分为非常满意、0~4分为一般满意、-5~-1分为不满意)从创面愈合、皮瓣形态、皮瓣感觉、皮瓣温度及日常功能方面调查患者的疗效满意度,并计算非常满意率;采用综合评价量表(优:皮瓣存活好,指功能恢复正常,感觉基本正常;良:皮瓣存活好,指功能基本恢复,感觉略有异常;中:皮瓣存活,指功能尚可,感觉未明显恢复;差:皮瓣未成活)评价皮瓣修复效果,并计算优良率。
2. 结果
2.1 总体情况
本组患者术后皮瓣和皮片均成活。术后随访10~18个月,皮瓣外观自然、不臃肿,存活良好,患指末梢温度、颜色与正常手指皮肤基本一致。末次随访时,患指关节功能恢复情况:11个患指关节活动度在正常范围,6个患指总主动活动度恢复到健侧的85%,3个患指总主动活动度恢复到健侧的75%。皮瓣感觉恢复情况:吻合神经的15个皮瓣感觉均恢复到S3 +级,皮瓣处皮肤两点辨别觉距离为7.0~9.0 mm(平均8.2 mm);未吻合神经的有1个皮瓣感觉恢复到S2级,4个皮瓣感觉恢复到S1级。20例患者的疗效满意度:非常满意者16例、一般满意者4例,非常满意率为80%;20个皮瓣修复效果:优16个、良2个、中2个,优良率为90%。
2.2 典型病例
例1
男,47岁,工作时左手示指接触1 kV高压电,导致指掌侧Ⅳ度电烧伤。伤后先在当地医院行保守治疗,伤后10 d转入本院。入院时体格检查见创面位于左手示指掌侧偏桡侧,面积约3.0 cm×2.0 cm,基底可见黑色腐肉样组织。伤后14 d,手术清除创面内坏死组织,可见示指桡侧固有血管和神经、指深屈肌腱缺损,近指间关节少许开放,中节指骨部分外露,清创后创面面积为4.5 cm×2.0 cm。应用患侧掌长肌腱修复指深屈肌腱缺损,采用面积为5.0 cm×2.5 cm健侧拇趾腓侧皮瓣携带拇趾背侧皮神经移植于左手示指掌侧创面,同前行血管、神经吻合。皮瓣供区移植大腿中厚皮覆盖。术后14 d拆线,术后4周皮瓣及皮片均存活良好。术后12个月末次随访时,皮瓣存活良好、外观自然、不臃肿,患指屈伸功能基本正常,皮瓣感觉达S3 +级,皮瓣处皮肤两点辨别觉距离为7.4 mm,患者对疗效表示非常满意,皮瓣修复效果为优。见 图1。
例2
男,22岁,工作时右手拇指接触1 kV高压电,导致指掌侧Ⅳ度电烧伤。伤后先在当地医院行保守治疗,伤后17 d转入本院。入院时体格检查见创面位于右手拇指掌侧,面积约6.0 cm×2.5 cm,基底可见黑色腐肉样组织。伤后20 d,手术清除创面内坏死组织,可见拇指指间关节开放,清创后创面面积为7.0 cm×3.0 cm。在健侧足部设计面积为8.0 cm×3.5 cm的足底内侧皮瓣,移植于右手拇指掌侧创面,同前行血管、神经吻合。皮瓣供区移植大腿中厚皮覆盖。术后14 d拆线,术后4周皮瓣及皮片均存活良好。术后14个月末次随访时,皮瓣外观自然、不臃肿,存活良好,患指屈伸功能基本正常,皮瓣感觉达S3 +级,皮瓣处皮肤两点辨别觉距离为8.2 mm,患者对疗效表示非常满意,皮瓣修复效果为优。见 图2。
3. 讨论
在手外伤中,手指电烧伤是比较严重的一种创伤。电烧伤对组织的损伤具有选择性,电阻较低的血管、神经、肌肉等组织损伤重,因此电烧伤常常伴有组织缺损、肌腱骨质外露,创面边界不清 [ 4, 5] ,创面基底受皮能力差,修复难度较大,严重时可能发生指坏死而导致截指,造成手部残疾。
对于手指的小面积电烧伤创面,黄书润等 [ 6] 尝试应用人工真皮+VSD联合自体皮移植修复,手术操作简单,术后手指外形好。但由于人工真皮移植对创面基底和创面面积要求较高,容易并发组织继发性坏死或感染等,该方法应用时受到基底血运的限制,且效果不如薄皮瓣好。也有学者应用传统或者改良的腹部皮瓣移植修复手指的电烧伤创面取得了较好的效果 [ 6, 7, 8, 9] 。但该方法需要制动上肢3周,术后患肢关节僵硬、皮瓣臃肿,需要多次手术修薄,且患者住院时间长 [ 10] 。还有报道应用指动脉逆行或顺行岛状皮瓣、掌背动脉皮瓣 [ 11, 12] 、邻指皮瓣 [ 13] 、鱼际皮瓣、V-Y推进皮瓣 [ 14, 15] 等修复手指电烧伤或外伤导致的皮肤缺损,修复后外形美观,但是局部损伤较大,皮瓣面积有限,术后也可能因瘢痕挛缩、关节僵直、创伤性关节炎等问题而导致各手指掌指关节、近指间关节和远指间关节的屈曲失能、背伸失能及关节强直,遗留手部功能障碍 [ 16, 17] 。
随着显微外科技术的不断普及,穿支皮瓣更加受到推崇,皮瓣切取面积越来越小,皮瓣供区也更加丰富,采用游离皮瓣修复手指电烧伤创面成为最有效和可靠的方法 [ 18] 。修复水平的提高促使修复方式向功能修复和外观修复发展。更多的游离微型皮瓣被应用到手指电烧伤创面修复中,如游离腕部或前臂穿支皮瓣 [ 19, 20] 、游离股前外侧穿支皮瓣 [ 21] 、动脉化血流桥接静脉皮瓣 [ 22, 23] 等。该类皮瓣的优点是皮瓣营养血管与受区血管口径匹配,同时由于皮瓣面积小,循环建立快,供区创面多可直接缝合。但手指结构复杂,指掌侧皮肤偏厚且皮纹深,皮下脂肪致密,防滑且耐磨、神经末梢丰富;而指背皮肤相对较薄,皮下组织少,皮肤褶皱丰富,弹性及延展性好,有利于手指的屈曲。所以应根据手指不同的部位选择合适的皮瓣进行修复,才能更好地恢复手指的功能及外观。
本研究遵从相似部位且具有相似功能的组织具有相似结构的原则 [ 24] ,应用足部微型皮瓣游离移植修复手指Ⅳ度电烧伤创面。修复时,针对指掌侧创面,应用足底内侧皮瓣或拇趾腓侧皮瓣进行修复,皮瓣组织与受区组织结构近似,同时吻合动静脉血管及神经,皮瓣血运有保障,感觉恢复快,能够达到功能修复的目的。而针对指背侧创面,选择应用足背动脉皮瓣修复,供区皮瓣组织与指背皮肤组织相似,皮下组织少、伸展性好,更加有利于手功能恢复,尽可能避免术后皮瓣修薄处理。本研究共纳入20处手指创面,均应用足部游离微型皮瓣来修复,大部分皮瓣达到较为满意的修复效果。吻合神经的皮瓣感觉恢复较快,术后12个月感觉即可达S3 +级;未吻合神经的皮瓣感觉恢复慢,术后18个月仅达S1、S2级。因此选择合适的皮瓣同时吻合神经对提高后期修复效果有不可忽视的作用。
手部功能是由5个手指协调作用的结果。根据手部功能评价标准将其功能系数分配为拇指40%,示指及中指各20%,环指及小指各10% [ 2] 。本研究选择拇指、示指及中指单一创面的修复进行讨论,是因为拇指、示指及中指的功能占全手功能的80%,这3个手指的修复对手功能的恢复意义更大。本组病例应用上述方案修复后,手指功能恢复至伤前或健侧手指功能的75%及以上,大部分患者对修复效果非常满意。
为了尽可能提高修复效果,本课题组认为有2点需要特别注意:(1)术中创面清创后,应首先探查受区血管射血情况,一般修复指掌侧创面需要在创面近端的指总血管处吻合,而修复指背侧创面则在鼻烟窝以远探查桡动脉终末支进行吻合,血流量方能满足移植皮瓣需要;(2)在皮瓣断蒂前要充分测量需要的血管蒂长度,避免皮瓣转移时血管蒂长度不足。
本研究表明,采用足部微型皮瓣游离移植修复手指Ⅳ度电烧伤创面具有较好的疗效,其优点在于:足部作为皮瓣供区位置隐蔽,皮瓣组织结构和功能与手指相似度高;术后皮瓣感染率、坏死率低;可切取多种类型皮瓣,可满足不同面积和形状的创面修复需求;术后患指功能恢复良好,疗效满意度高。
尽管足部微型皮瓣游离移植在手指Ⅳ度电烧伤创面修复中表现出较好的疗效,但仍存在一些挑战和限制。首先,该术式对操作者的技术水平要求较高,需要操作者具备丰富显微外科经验。手术过程中须精确吻合血管,以保证皮瓣的存活和创面的有效修复;其次,术后抗感染、抗凝等治疗同样重要,需严格遵守医嘱,进行系统治疗;再者,由于电烧伤创面的特殊性,可能存在深部组织损伤和神经损伤,因此术后功能恢复可能需要较长时间;最后,在临床实践中,应根据患者的具体情况选择最合适的治疗方法。因此,未来的研究应进一步探讨足部游离微型皮瓣在手指电烧伤创面修复中的应用范围和限制。同时,应研究更先进的技术和治疗方法,以提高皮瓣的成活率和功能恢复效果。此外,应加强临床护理和康复治疗,促进患者的手指功能恢复,改善患者生活质量。
综上所述,采用足部微型皮瓣游离移植修复手指Ⅳ度电烧伤创面是一种有效的治疗方法,值得临床推广。但仍需在临床实践中不断探索和改进,以进一步提高治疗效果,为患者提供更好的治疗体验和生活质量。
所有作者均声明不存在利益冲突慢性感染状态在难愈性创面中经常存在,而导致感染难以清除的主要原因是细菌生物膜,复杂的创面细菌生物膜明显削弱了抗菌药物的效力,使得使用传统抗菌敷料和全身抗菌药治疗这些难愈性创面的临床疗效并不确切。抗菌敷料比抗生素更有优势,因为它们具有更广谱的活性,且抗菌剂仅在局部创面环境中有活性,发生微生物耐药性的可能性显著降低。因此,在没有临床感染扩散迹象的情况下,抗菌敷料应被视为标准护理中创面感染管理的一线方法。解决创面处理中抗生素的过度使用是当务之急,使用适当的抗菌敷料是抗生素管理工作的重要考虑因素。英国 ConvaTec(康维德)公司Daniel G. Metcalf在《Burns & Trauma》发文《Clinical impact of an anti-biofilm Hydrofiber dressing in hard-to-heal wounds previously managed with traditional antimicrobial products and systemic antibiotics》,该研究阐述了新一代抗细菌生物膜水力纤维敷料[AQUACEL Ag+ Extra(AQAg+ E)]在难愈性创面中的临床疗效。该抗细菌生物膜敷料包含金属螯合剂和表面活性剂组分,是一种含银离子型羧甲基纤维素敷料。金属螯合剂和表面活性剂与银离子有协同作用,破坏细菌生物膜结构,使银离子能够进入并杀死生物膜结构内的微生物。该研究进行了抗细菌生物膜敷料的临床案例评估,其中临床医师选择恶化或停滞的创面,更换原来的敷料,使用该抗细菌生物膜敷料长达4周时间,并持续监测和评估。同时在使用抗细菌生物膜敷料之前,对传统含银、碘或聚六亚甲基双胍盐酸盐敷料以及全身抗生素治疗的病例数据进行了分层分析。结果显示,65例患者创面经过平均4.2周的抗生物膜敷料治疗后,其中11例(17%)创面愈合,40例(62%)创面好转,9例(14%)创面保持不变,5例(8%)创面恶化。该研究表明,采用抗细菌生物膜技术合成的含银离子敷料可能是比传统抗菌材料和抗生素更优的选择,该敷料能够破坏细菌生物膜消灭细菌,从而治疗难愈性感染创面,有较好的临床疗效。王杨平,编译自《Burns Trauma》,2020,8:tkaa004;罗高兴,审校 -
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表1 当前临床所使用的创面敷料简介
种类 组成 特点 适应证 凡士林油纱 纤维素和凡士林 廉价、干燥、需多次换药,易造成二次伤害 广泛使用,但在复杂创面治疗时需配合其他操作或药物 水凝胶敷料 三维亲水聚合物网络 渗出液吸收性强、优异的保湿性能(有利于清理坏死组织)、透明材质(可直接观察创面)、可负载活性分子、方便去除及换药 干燥至中等量渗出液的非感染创面 水胶体敷料 水凝胶与合成橡胶以及黏性聚合物复合而成 渗出液吸收性强、优异的保湿性能(有利于清理坏死组织)、皮肤黏合性良好,可用于关节处 中等量渗出液的非感染创面 藻酸盐类敷料 褐藻内提取的多糖 渗出液吸收性优异(吸收后成水凝胶态)、止血 中等量至大量渗出液的感染或非感染创面 海绵(泡沫)敷料 硅胶或聚氨酯 半透过性(可阻隔细菌)、保温保湿 中等量至大量渗出液的非感染创面 薄膜敷料 胶黏剂和多孔透明聚氨酯薄膜 透气性好、隔绝水和细菌 渗出液较少的表面浅层非感染创面、上皮化创面 -
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