仿生聚乳酸/明胶纳米纤维膜修复下肢静脉曲张溃疡
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摘要
背景:受限于有效治疗手段的缺乏,下肢静脉溃疡迁延不愈,容易反复,对患者的生活产生严重影响;动物实验已证实仿生聚乳酸/明胶纳米纤维膜在皮肤缺损组织再生修复中具有明显优势。目的:观察仿生聚乳酸/明胶纳米纤维膜修复下肢静脉曲张溃疡的效果。方法:纳入2017年11月至2018年11月安徽医科大学第一附属医院收治的下肢静脉溃疡患者60例,采用随机数字表法分为对照组和试验组,每组30例,所有患者前期均给予清创和基础治疗,对照组给予常规换药,试验组是在常规处理的基础上采用仿生聚乳酸/明胶纳米纤维膜换药。每周记录并比较两组的创面愈合率、愈合时间、换药次数、创面疼痛评分、敷料二次创伤积分、操作难易性、安全性和患者满意度;溃疡创面愈合后6个月,采用温哥华瘢痕评定量表对后期修复效果进行评价。试验已通过安徽医科大学第一附属医院伦理委员会批准,伦理批准号:安医一附伦审-快-PJ2018-01-09。结果与结论:(1)试验组换药后28 d的创面愈合率、患者满意度均高于对照组(P <0.05),创面愈合时间、换药次数、创面疼痛评分、敷料二次创伤积分、操作难易性评分明显低于对照组(P <0.05);(2)溃疡创面愈合后6个月,对照组为瘢痕评分明显高于试验组(P <0.05);(3)换药期间及创面愈合后6个月,两组均未见肝肾损伤,未发生局部过敏等不良反应;(4)结果表明仿生聚乳酸/明胶纳米纤维膜是安全、有效的,可显著缩短创面愈合时间、减少换药次数、降低创面换药时的疼痛感和二次创伤、方便临床医护人员使用、提高患者舒适度和满意度。
BACKGROUND: Insufficient effective treatments lead to protracted course and recurrence of lower extremity venous ulcers, greatly influencing patient's life. Animal experiments have confirmed that bionic polylactic acid/gelatin nanofiber membrane has advantages in the repair of deficient skin tissue.OBJECTIVE: To investigate the efficacy of bionic polylactic acid/gelatin nanofiber membrane in the repair of varicose ulcers in the lower extremities.METHODS: Sixty patients with varicose ulcers in the lower extremities admitted to the First Affiliated Hospital of Anhui Medical University,China from November 2017 to November 2018 were randomly divided into a control group and an experimental group, with 30 cases in each group. All patients were given debridement and basic treatment in the early stage. Patients in the control group received conventional dressing. Patients in the experimental group received bionic polylactic acid/gelatin nanofiber membrane dressing based on conventional dressing. Wound healing rate, healing time, dressing change frequency, wound pain average score, dressing-caused secondary wound score,ease of operation, safety and patient satisfaction were recorded and compared between the two groups every week. At 6 months after wound healing, post-repair effect was evaluated using the Vancouver Scar Rating Scale. This study was approved by the Ethics Committee, First Affiliated Hospital of Anhui Medical University, China(approval No. PJ2018-01-09).RESULTS AND CONCLUSION: At 28 days after dressing, wound healing rate and patient satisfaction in the experimental group were significantly greater than those in the control group(P < 0.05). Healing time, dressing change frequency, wound pain average score,dressing-caused secondary wound score, and ease of operation in the experimental group were significantly lower than those in the control group(P < 0.05). Six months after wound healing, scale score in the control group was significantly higher than that in the experimental group(P < 0.05). During dressing and 6 months after wound healing, there were no liver and kidney injuries in the two groups. In addition, no reverse reactions such as local allergy were observed in either group. These results suggest that bionic polylactic acid/gelatin nanofiber membrane for repairing ulcers in patients with lower extremity varicose veins is safe and effective. It can greatly shorten the wound healing time, reduce dressing change frequency, mitigate pain and secondary trauma during wound dressing change, and provide the ease of use by clinical medical staff, and improve patient comfort and satisfaction.
BACKGROUND: Insufficient effective treatments lead to protracted course and recurrence of lower extremity venous ulcers, greatly influencing patient's life. Animal experiments have confirmed that bionic polylactic acid/gelatin nanofiber membrane has advantages in the repair of deficient skin tissue.OBJECTIVE: To investigate the efficacy of bionic polylactic acid/gelatin nanofiber membrane in the repair of varicose ulcers in the lower extremities.METHODS: Sixty patients with varicose ulcers in the lower extremities admitted to the First Affiliated Hospital of Anhui Medical University,China from November 2017 to November 2018 were randomly divided into a control group and an experimental group, with 30 cases in each group. All patients were given debridement and basic treatment in the early stage. Patients in the control group received conventional dressing. Patients in the experimental group received bionic polylactic acid/gelatin nanofiber membrane dressing based on conventional dressing. Wound healing rate, healing time, dressing change frequency, wound pain average score, dressing-caused secondary wound score,ease of operation, safety and patient satisfaction were recorded and compared between the two groups every week. At 6 months after wound healing, post-repair effect was evaluated using the Vancouver Scar Rating Scale. This study was approved by the Ethics Committee, First Affiliated Hospital of Anhui Medical University, China(approval No. PJ2018-01-09).RESULTS AND CONCLUSION: At 28 days after dressing, wound healing rate and patient satisfaction in the experimental group were significantly greater than those in the control group(P < 0.05). Healing time, dressing change frequency, wound pain average score,dressing-caused secondary wound score, and ease of operation in the experimental group were significantly lower than those in the control group(P < 0.05). Six months after wound healing, scale score in the control group was significantly higher than that in the experimental group(P < 0.05). During dressing and 6 months after wound healing, there were no liver and kidney injuries in the two groups. In addition, no reverse reactions such as local allergy were observed in either group. These results suggest that bionic polylactic acid/gelatin nanofiber membrane for repairing ulcers in patients with lower extremity varicose veins is safe and effective. It can greatly shorten the wound healing time, reduce dressing change frequency, mitigate pain and secondary trauma during wound dressing change, and provide the ease of use by clinical medical staff, and improve patient comfort and satisfaction.
引文
[1]Lin YN,Hsieh TY,Huang SH,et al.Management of venous ulcers according to their anatomical relationship with varicose veins.Phlebology.2018;33(1):44-52.
[2]Pascarella L,Shortell CK.Medical management of venous ulcers.Semin Vasc Surg.2015;28(1):21-28.
[3]Finlayson KJ,Parker CN,Miller C,et al.Predicting the likelihood of venous leg ulcer recurrence:The diagnostic accuracy of a newly developed risk assessment tool.Int Wound J.2018;15(5):686-694.
[4]Branisteanu DE,Feodor T,Baila S,et al.Impact of chronic venous disease on quality of life:Results of vein alarm study.Exp Ther Med.2019;17(2):1091-1096.
[5]Xie T,Ye J,Rerkasem K,et al.The venous ulcer continues to be a clinical challenge:an update.Burns Trauma.2018;6:18.
[6]Todd M.Assessment and management of older people with venous leg ulcers.Nurs Older People.2018;30(5):39-48.
[7]Cowan T.Strategies for improving outcomes in venous leg ulcer care.J Wound Care.2018;27(7):456-457.
[8]Applewhite A,Chowdhry SA,Desvigne M,et al.Inpatient and Outpatient Wound Treatment Recommendations:Assessing Use of Negative Pressure Wound Therapy Systems or Oxidized Regenerated Cellulose(ORC)/Collagen/Silver-ORC Dressings.Wounds.2018;30(8 supp):S19-S35.
[9]Murray RZ,West ZE,Cowin AJ,et al.Development and use of biomaterials as wound healing therapies.Burns Trauma.2019;7:2.
[10]García-Lizarribar A,Fernández-Garibay X,Velasco-MallorquíF,et al.Composite Biomaterials as Long-Lasting Scaffolds for3D Bioprinting of Highly Aligned Muscle Tissue.Macromol Biosci.2018;18(10):e1800167.
[11]Wang J,Wang Y,Liu D,et al.Preparation and cytological study of collagen/nano-hydroxyapatite/graphene oxide composites.Acta Bioeng Biomech.2018;20(4):65-74.
[12]Zhang Z,Guo W,Gao S,et al.Native tissue-based strategies for meniscus repair and regeneration.Cell Tissue Res.2018;373(2):337-350.
[13]Sun H,Lv H,Qiu F,et al.Clinical application of a 3D-printed scaffold in chronic wound treatment:a case series J Wound Care.2018;27(5):262-271.
[14]Ming L,Zhipeng Y,Fei Y,et al.Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.Artif Cells Nanomed Biotechnol.2018;46(sup1):336-346.
[15]Yu F,Li M,Yuan Z,et al.Mechanism research on a bioactive resveratrol-PLA-gelatin porous nano-scaffold in promoting the repair of cartilage defect.Int J Nanomedicine.2018;13:7845-7858.
[16]陈洪让,张海涛,李永生,等.手持静电纺丝可降解纳米纤维原位组织修复的实验研究[J].中国组织工程研究,2019,23(2):257-264.
[17]柳芳芹.压力治疗系统管理在下肢静脉溃疡湿性愈合中的应用效果观察[J].齐鲁护理杂志,2012,18(23):31-32.
[18]Harries RL,Bosanquet DC,Harding KG.Wound bed preparation:TIME for an update.Int Wound J.2016;13 Suppl3:8-14.
[19]Cazzell S.A Randomized Controlled Trial Comparing a Human Acellular Dermal Matrix Versus Conventional Care for the Treatment of Venous Leg Ulcers.Wounds.2019;31(3):68-74.
[20]Briggs M,Ferris FD,Glynn C,et al.World Union of Wound Healing Societies EXPERT WORKING GROUP.Assessing pain at wound dressing-related procedures.Nurs Times.2004;100(41):56-57.
[21]中华人民共和国卫生部.中药新药临床研巧指导原则.北京:中国医药科技出版社,2002:68-73.
[22]Finlay V,Burrows S,Kendell R,et al.Modified Vancouver Scar Scale score is linked with quality of life after burn.Burns.2017;43(4):741-746.
[23]Dash BC,Xu Z,Lin L,et al.Stem Cells and Engineered Scaffolds for Regenerative Wound Healing.Bioengineering(Basel).2018;5(1).pii:E23.doi:10.3390/bioengineering5010023.
[24]Lien SM,Ko LY,Huang TJ.Effect of pore size on ECMsecretion and cell growth in gelatin scaffold for articular cartilage tissue engineering.Acta Biomater.2009;5(2):670-679.
[25]Hoveizi E,Ebrahimi-Barough S,Tavakol S,et al.In Vitro Differentiation of Human iPS Cells into Neural like Cells on a Biomimetic Polyurea.Mol Neurobiol.2017;54(1):601-607.
[26]Kim HW,Yu HS,Lee HH.Nanofibrous matrices of poly(lactic acid)and gelatin polymeric blends for the improvement of cellular responses.J Biomed Mater Res A.2008;87(1):25-32.
[27]Wang S,Zhang Y,Wang H,et al.Fabrication and properties of the electrospun polylactide/silk fibroin-gelatin composite tubular scaffold.Biomacromolecules.2009;10(8):2240-2244.
[28]Chiou BS,Jafri H,Avena-Bustillos R,et al.Properties of electrospun pollock gelatin/poly(vinyl alcohol)and pollock gelatin/poly(lactic acid)fibers.Int J Biol Macromol.2013;55:214-220.
[29]Paschoalin RT,Traldi B,Aydin G,et al.Solution blow spinning fibres:New immunologically inert substrates for the analysis of cell adhesion and motility.Acta Biomater.2017;51:161-174.
[30]Aldana AA,Abraham GA.Current advances in electrospun gelatin-based scaffolds for tissue engineering applications.Int J Pharm.2017;523(2):441-453.
[31]Ye K,Liu D,Kuang H,et al.Three-dimensional electrospun nanofibrous scaffolds displaying bone morphogenetic protein-2-derived peptides for the promotion of osteogenic differentiation of stem cells and bone regeneration.J Colloid Interface Sci.2019;534:625-636.
[32]Deng K,Yang Y,Ke Y,et al.A novel biomimetic composite substitute of PLLA/gelatin nanofiber membrane for dura repairing.Neurol Res.2017;39(9):819-829.
[33]Liu Y,Cui H,Zhuang X,et al.Electrospinning of aniline pentamer-graft-gelatin/PLLA nanofibers for bone tissue engineering.Acta Biomater.2014;10(12):5074-5080.
[34]Zhang C,Cao M,Lan J,et al.Regulating proliferation and differentiation of osteoblasts on poly(l-lactide)/gelatin composite nanofibers via timed biomineralization.J Biomed Mater Res A.2016;104(8):1968-1980.
[35]Piran M,Shiri M,Soufi Zomorrod M,et al.Electrospun triple-layered PLLA/gelatin.PRGF/PLLA scaffold induces fibroblast migration.J Cell Biochem.2019.doi:10.1002/jcb.28422.[Epub ahead of print]
[36]Amjadian S,Seyedjafari E,Zeynali B,et al.The synergistic effect of nano-hydroxyapatite and dexamethasone in the fibrous delivery system of gelatin and poly(l-lactide)on the osteogenesis of mesenchymal stem cells.Int J Pharm.2016;507(1-2):1-11.
[37]Nair HKR.Microcurrent as an adjunct therapy to accelerate chronic wound healing and reduce patient pain.J Wound Care.2018;27(5):296-306.
[38]Frescos N.Assessment of pain in chronic wounds:A survey of Australian health care practitioners.Int Wound J.2018;15(6):943-949.
[39]Upton D,Solowiej K,Hender C,et al.Stress and pain associated with dressing change in patients with chronic wounds.J Wound Care.2012;21(2):53-54,56,58 passim.
[40]H?glund A,Hakkarainen M,Edlund U,et al.Surface modification changes the degradation process and degradation product pattern of polylactide.Langmuir.2010;26(1):378-383.
[41]Echave MC,Saenz del Burgo L,Pedraz JL,et al.Gelatin as Biomaterial for Tissue Engineering.Curr Pharm Des.2017;23(24):3567-3584.
[2]Pascarella L,Shortell CK.Medical management of venous ulcers.Semin Vasc Surg.2015;28(1):21-28.
[3]Finlayson KJ,Parker CN,Miller C,et al.Predicting the likelihood of venous leg ulcer recurrence:The diagnostic accuracy of a newly developed risk assessment tool.Int Wound J.2018;15(5):686-694.
[4]Branisteanu DE,Feodor T,Baila S,et al.Impact of chronic venous disease on quality of life:Results of vein alarm study.Exp Ther Med.2019;17(2):1091-1096.
[5]Xie T,Ye J,Rerkasem K,et al.The venous ulcer continues to be a clinical challenge:an update.Burns Trauma.2018;6:18.
[6]Todd M.Assessment and management of older people with venous leg ulcers.Nurs Older People.2018;30(5):39-48.
[7]Cowan T.Strategies for improving outcomes in venous leg ulcer care.J Wound Care.2018;27(7):456-457.
[8]Applewhite A,Chowdhry SA,Desvigne M,et al.Inpatient and Outpatient Wound Treatment Recommendations:Assessing Use of Negative Pressure Wound Therapy Systems or Oxidized Regenerated Cellulose(ORC)/Collagen/Silver-ORC Dressings.Wounds.2018;30(8 supp):S19-S35.
[9]Murray RZ,West ZE,Cowin AJ,et al.Development and use of biomaterials as wound healing therapies.Burns Trauma.2019;7:2.
[10]García-Lizarribar A,Fernández-Garibay X,Velasco-MallorquíF,et al.Composite Biomaterials as Long-Lasting Scaffolds for3D Bioprinting of Highly Aligned Muscle Tissue.Macromol Biosci.2018;18(10):e1800167.
[11]Wang J,Wang Y,Liu D,et al.Preparation and cytological study of collagen/nano-hydroxyapatite/graphene oxide composites.Acta Bioeng Biomech.2018;20(4):65-74.
[12]Zhang Z,Guo W,Gao S,et al.Native tissue-based strategies for meniscus repair and regeneration.Cell Tissue Res.2018;373(2):337-350.
[13]Sun H,Lv H,Qiu F,et al.Clinical application of a 3D-printed scaffold in chronic wound treatment:a case series J Wound Care.2018;27(5):262-271.
[14]Ming L,Zhipeng Y,Fei Y,et al.Microfluidic-based screening of resveratrol and drug-loading PLA/Gelatine nano-scaffold for the repair of cartilage defect.Artif Cells Nanomed Biotechnol.2018;46(sup1):336-346.
[15]Yu F,Li M,Yuan Z,et al.Mechanism research on a bioactive resveratrol-PLA-gelatin porous nano-scaffold in promoting the repair of cartilage defect.Int J Nanomedicine.2018;13:7845-7858.
[16]陈洪让,张海涛,李永生,等.手持静电纺丝可降解纳米纤维原位组织修复的实验研究[J].中国组织工程研究,2019,23(2):257-264.
[17]柳芳芹.压力治疗系统管理在下肢静脉溃疡湿性愈合中的应用效果观察[J].齐鲁护理杂志,2012,18(23):31-32.
[18]Harries RL,Bosanquet DC,Harding KG.Wound bed preparation:TIME for an update.Int Wound J.2016;13 Suppl3:8-14.
[19]Cazzell S.A Randomized Controlled Trial Comparing a Human Acellular Dermal Matrix Versus Conventional Care for the Treatment of Venous Leg Ulcers.Wounds.2019;31(3):68-74.
[20]Briggs M,Ferris FD,Glynn C,et al.World Union of Wound Healing Societies EXPERT WORKING GROUP.Assessing pain at wound dressing-related procedures.Nurs Times.2004;100(41):56-57.
[21]中华人民共和国卫生部.中药新药临床研巧指导原则.北京:中国医药科技出版社,2002:68-73.
[22]Finlay V,Burrows S,Kendell R,et al.Modified Vancouver Scar Scale score is linked with quality of life after burn.Burns.2017;43(4):741-746.
[23]Dash BC,Xu Z,Lin L,et al.Stem Cells and Engineered Scaffolds for Regenerative Wound Healing.Bioengineering(Basel).2018;5(1).pii:E23.doi:10.3390/bioengineering5010023.
[24]Lien SM,Ko LY,Huang TJ.Effect of pore size on ECMsecretion and cell growth in gelatin scaffold for articular cartilage tissue engineering.Acta Biomater.2009;5(2):670-679.
[25]Hoveizi E,Ebrahimi-Barough S,Tavakol S,et al.In Vitro Differentiation of Human iPS Cells into Neural like Cells on a Biomimetic Polyurea.Mol Neurobiol.2017;54(1):601-607.
[26]Kim HW,Yu HS,Lee HH.Nanofibrous matrices of poly(lactic acid)and gelatin polymeric blends for the improvement of cellular responses.J Biomed Mater Res A.2008;87(1):25-32.
[27]Wang S,Zhang Y,Wang H,et al.Fabrication and properties of the electrospun polylactide/silk fibroin-gelatin composite tubular scaffold.Biomacromolecules.2009;10(8):2240-2244.
[28]Chiou BS,Jafri H,Avena-Bustillos R,et al.Properties of electrospun pollock gelatin/poly(vinyl alcohol)and pollock gelatin/poly(lactic acid)fibers.Int J Biol Macromol.2013;55:214-220.
[29]Paschoalin RT,Traldi B,Aydin G,et al.Solution blow spinning fibres:New immunologically inert substrates for the analysis of cell adhesion and motility.Acta Biomater.2017;51:161-174.
[30]Aldana AA,Abraham GA.Current advances in electrospun gelatin-based scaffolds for tissue engineering applications.Int J Pharm.2017;523(2):441-453.
[31]Ye K,Liu D,Kuang H,et al.Three-dimensional electrospun nanofibrous scaffolds displaying bone morphogenetic protein-2-derived peptides for the promotion of osteogenic differentiation of stem cells and bone regeneration.J Colloid Interface Sci.2019;534:625-636.
[32]Deng K,Yang Y,Ke Y,et al.A novel biomimetic composite substitute of PLLA/gelatin nanofiber membrane for dura repairing.Neurol Res.2017;39(9):819-829.
[33]Liu Y,Cui H,Zhuang X,et al.Electrospinning of aniline pentamer-graft-gelatin/PLLA nanofibers for bone tissue engineering.Acta Biomater.2014;10(12):5074-5080.
[34]Zhang C,Cao M,Lan J,et al.Regulating proliferation and differentiation of osteoblasts on poly(l-lactide)/gelatin composite nanofibers via timed biomineralization.J Biomed Mater Res A.2016;104(8):1968-1980.
[35]Piran M,Shiri M,Soufi Zomorrod M,et al.Electrospun triple-layered PLLA/gelatin.PRGF/PLLA scaffold induces fibroblast migration.J Cell Biochem.2019.doi:10.1002/jcb.28422.[Epub ahead of print]
[36]Amjadian S,Seyedjafari E,Zeynali B,et al.The synergistic effect of nano-hydroxyapatite and dexamethasone in the fibrous delivery system of gelatin and poly(l-lactide)on the osteogenesis of mesenchymal stem cells.Int J Pharm.2016;507(1-2):1-11.
[37]Nair HKR.Microcurrent as an adjunct therapy to accelerate chronic wound healing and reduce patient pain.J Wound Care.2018;27(5):296-306.
[38]Frescos N.Assessment of pain in chronic wounds:A survey of Australian health care practitioners.Int Wound J.2018;15(6):943-949.
[39]Upton D,Solowiej K,Hender C,et al.Stress and pain associated with dressing change in patients with chronic wounds.J Wound Care.2012;21(2):53-54,56,58 passim.
[40]H?glund A,Hakkarainen M,Edlund U,et al.Surface modification changes the degradation process and degradation product pattern of polylactide.Langmuir.2010;26(1):378-383.
[41]Echave MC,Saenz del Burgo L,Pedraz JL,et al.Gelatin as Biomaterial for Tissue Engineering.Curr Pharm Des.2017;23(24):3567-3584.