Frontier progress in complex wound repair: from microenvironment regulation to precision medical practice
-
摘要: 复杂创面的高发病率、高致残率以及高昂的医疗成本,给患者和医疗系统带来巨大负担。传统复杂创面治疗方法存在局限性,因此需要进一步完善或建立新的诊断与治疗策略以应对这一临床难题。该文回顾和讨论复杂创面修复领域的重要进展,以及现代创面修复体系构建中的新理念,旨在为临床医护、科研人员及相关产业人员提供参考,推动复杂创面修复领域的持续发展,最终实现复杂创面患者功能与美学的全面修复。Abstract: Complex wounds, with high incidence rate, high disability rate, and high medical costs, have brought huge burdens to patients and medical systems. Traditional treatment methods of complex wounds have limitations, therefore it is necessary to further improve and develop innovative strategies of diagnosis and treatment to address this clinical challenge. This article reviews and discusses important advances in the field of complex wound repair, as well as new concepts in the construction of modern wound management systems. The aim is to provide a reference for clinical medical staff, researchers, and related industry personnel, promote the sustainable development of complex wound repair field, and ultimately achieve comprehensive recovery of function and aesthetics of patients with complex wounds.
-
参考文献
(50) [1] ArmstrongDG,TanTW,BoultonAJM,et al.Diabetic foot ulcers: a review[J].JAMA,2023,330(1):62-75.DOI: 10.1001/jama.2023.10578. [2] TriccoAC,AntonyJ,VafaeiA,et al.Seeking effective interventions to treat complex wounds: an overview of systematic reviews[J].BMC Med,2015,13:89.DOI: 10.1186/s12916-015-0288-5. [3] KantorJ,MargolisDJ.A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks[J].Br J Dermatol,2000,142(5):960-964.DOI: 10.1046/j.1365-2133.2000.03478.x. [4] 姚泽欣,付小兵,程飚.慢性创面愈合新理念:姑息性创面治疗的研究进展[J].中华烧伤杂志,2020,36(8):754-757.DOI: 10.3760/cma.j.cn501120-20190929-00388. [5] JiangY,HuangS,FuX,et al.Epidemiology of chronic cutaneous wounds in China[J].Wound Repair Regen,2011,19(2):181-188.DOI: 10.1111/j.1524-475X.2010.00666.x. [6] 潘选良,韩春茂.《优化技术在下肢慢性创面愈合中的应用共识》简介[J].中华烧伤杂志,2017,33(9):589-591.DOI: 10.3760/cma.j.issn.1009-2587.2017.09.017. [7] ZhangY,AlexanderPB,WangXF.TGF-β family signaling in the control of cell proliferation and survival[J].Cold Spring Harb Perspect Biol,2017,9(4):a022145.DOI: 10.1101/cshperspect.a022145. [8] ZhaoR,LiangH,ClarkeE,et al.Inflammation in chronic wounds[J].Int J Mol Sci,2016,17(12):2085.DOI: 10.3390/ijms17122085. [9] Di MiccoR,KrizhanovskyV,BakerD,et al.Cellular senescence in ageing: from mechanisms to therapeutic opportunities[J].Nat Rev Mol Cell Biol,2021,22(2):75-95.DOI: 10.1038/s41580-020-00314-w. [10] Al MamunA,ShaoC,GengP,et al.Recent advances in the role of neuroregulation in skin wound healing[J/OL].Burns Trauma,2025,13:tkae072[2025-04-07].https://pubmed.ncbi.nlm.nih.gov/39872039/.DOI: 10.1093/burnst/tkae072. [11] 韩飞, 张万福, 佟琳, 等. 阔筋膜-股前外侧皮瓣复合移植修复颌面部根治性肿瘤切除术后复杂缺损的临床效果[J]. 中华烧伤与创面修复杂志, 2025, 41(5):440-446. DOI: 10.3760/cma.j.cn501225-20240801-00290. [12] ChenW,HazoorS,MadiganR,et al.Alkaline-responsive polydiacetylene-peptide hydrogel for pH-sensing and on-demand antimicrobial release[J].Mater Today Adv,2022,16: 100288.DOI: 10.1016/j.mtadv.2022.100288. [13] AminM,LammersT,Ten HagenTLM.Temperature-sensitive polymers to promote heat-triggered drug release from liposomes: towards bypassing EPR[J].Adv Drug Deliv Rev,2022,189:114503.DOI: 10.1016/j.addr.2022.114503. [14] Raeeszadeh-SarmazdehM, DoLD, HritzBG.Metalloproteinases and their inhibitors: potential for the development of new therapeutics[J].Cells,2020,9(5):1313.DOI: 10.3390/cells9051313. [15] LigorioC,MataA.Synthetic extracellular matrices with function-encoding peptides[J]. Nat Rev Bioeng,2023,1(7): 518-536.DOI: 10.1038/s44222-023-00055-3. [16] MishraA,ModiU,SharmaR,et al.Biochemical and biophysical cues of the extracellular matrix modulates stem cell fate: progress and prospect in extracellular matrix mimicking biomaterials[J]. Biomed Eng Adv,2025,9:100143. DOI: 10.1016/j.bea.2024.100143. [17] WuF,RenY,LvW,et al.Generating dual structurally and functionally skin-mimicking hydrogels by crosslinking cell-membrane compartments[J].Nat Commun,2024,15(1):802.DOI: 10.1038/s41467-024-45006-7. [18] HamaR,ReinhardtJW,UlziibayarA,et al.Recent tissue engineering approaches to mimicking the extracellular matrix structure for skin regeneration[J].Biomimetics (Basel),2023,8(1):130.DOI: 10.3390/biomimetics8010130. [19] TavafoghiM,DarabiMA,MahmoodiM,et al.Multimaterial bioprinting and combination of processing techniques towards the fabrication of biomimetic tissues and organs[J]. Biofabrication,2021,13(4):042002. DOI: 10.1088/1758-5090/ac0b9a. [20] KhoeiniR,NosratiH,AkbarzadehA,et al.Natural and synthetic bioinks for 3D bioprinting[J].Adv NanoBiomed Res,2021,1(8):2000097.DOI: 10.1002/anbr.202000097. [21] LiangX,DingY,ZhangY,et al.Paracrine mechanisms of mesenchymal stem cell-based therapy: current status and perspectives[J].Cell Transplant,2014,23(9):1045-1059.DOI: 10.3727/096368913X667709. [22] HoseiniSM,MontazeriF.Cell origin and microenvironment: the players of differentiation capacity in human mesenchymal stem cells[J].Tissue Cell,2025,93:102709.DOI: 10.1016/j.tice.2024.102709. [23] GuoL,XiaoD,XingH,et al.Engineered exosomes as a prospective therapy for diabetic foot ulcers[J/OL].Burns Trauma,2024,12:tkae023[2025-04-07].https://academic.oup.com/burnstrauma/article/doi/ 10.1093/burnst/tkae023/7715755.DOI: 10.1093/burnst/tkae023. [24] YuanX,LiL,LiuH,et al.Strategies for improving adipose-derived stem cells for tissue regeneration[J/OL].Burns Trauma,2022,10:tkac028[2025-04-07].https://academic.oup.com/burnstrauma/article/doi/ 10.1093/burnst/tkac028/6668137.DOI: 10.1093/burnst/tkac028. [25] FakouriA,RazaviZS,MohammedAT,et al.Applications of mesenchymal stem cell-exosome components in wound infection healing: new insights[J/OL].Burns Trauma,2024,12:tkae021[2025-04-07]. https://academic.oup.com/burnstrauma/article/doi/ 10.1093/burnst/tkae021/7731845.DOI: 10.1093/burnst/tkae021. [26] LauHC,HanDW,ParkJ,et al.GMP-compliant manufacturing of biologically active cell-derived vesicles produced by extrusion technology[J].J Extracell Biol,2022,1(12):e70.DOI: 10.1002/jex2.70. [27] LingS,ZhangX,DaiY,et al.Customizable virus-like particles deliver CRISPR-Cas9 ribonucleoprotein for effective ocular neovascular and Huntington's disease gene therapy[J]. Nat Nanotechnol,2025,20(4):543-553.DOI: 10.1038/s41565-024-01851-7. [28] HeX,WangD,YiY,et al.δ-Tocotrienol preconditioning improves the capability of bone marrow-derived mesenchymal stem cells in promoting wound healing by inhibiting BACH1-related ferroptosis[J].Cell Death Discov,2023,9(1):349.DOI: 10.1038/s41420-023-01653-1. [29] MilasinovicS,LiuY,GasperGL,et al.Ultrashort pulse laser ablation for depth profiling of bacterial biofilms[J].J Vac Sci Technol A,2010,28(4):647-651.DOI: 10.1116/1.3397736. [30] WuS,XuC,ZhuY,et al.Biofilm‐sensitive photodynamic nanoparticles for enhanced penetration and antibacterial efficiency[J].Adv Funct Mater,2021,31(33):2103591. DOI: 10.1002/adfm.202103591. [31] WangS,ZhaoY,BreslawecAP,et al.Strategy to combat biofilms: a focus on biofilm dispersal enzymes[J].NPJ Biofilms Microbiomes,2023,9(1):63.DOI: 10.1038/s41522-023-00427-y. [32] Ali AghaASA,Al-SamydaiA,AburjaiT.New frontiers in CRISPR: addressing antimicrobial resistance with Cas9, Cas12, Cas13, and Cas14[J].Heliyon,2025,11(2):e42013. DOI: 10.1016/j.heliyon.2025.e42013. [33] BarzegariA,KheyrolahzadehK,Hosseiniyan KhatibiSM,et al.The battle of probiotics and their derivatives against biofilms[J].Infect Drug Resist,2020,13:659-672.DOI: 10.2147/IDR.S232982. [34] KaisthaSD,DeshpandeN.Traditional probiotics, next-generation probiotics and engineered live biotherapeutic products in chronic wound healing[M]//Kumar P,Kothari V.Wound healing research. Singapore: Springer Singapore,2021:247-284. DOI: 10.1007/978-981-16-2677-7_8. [35] AlexanderM,HuR,RuntschMC,et al.Exosome-delivered microRNAs modulate the inflammatory response to endotoxin[J].Nat Commun,2015,6:7321.DOI: 10.1038/ncomms8321. [36] NailHM,ChiuCC,LeungCH,et al.Exosomal miRNA-mediated intercellular communications and immunomodulatory effects in tumor microenvironments[J].J Biomed Sci,2023,30(1):69.DOI: 10.1186/s12929-023-00964-w. [37] WitherelCE,AbebayehuD,BarkerTH,et al.Macrophage and fibroblast interactions in biomaterial-mediated fibrosis[J].Adv Healthc Mater,2019,8(4):e1801451.DOI: 10.1002/adhm.201801451. [38] ParkW,ParkS,ParkKY,et al.Long-term antioxidant metal-organic frameworks[J].ACS Omega,2024,9(19):21484-21493.DOI: 10.1021/acsomega.4c01993. [39] XuF,FeringaBL.Photoresponsive supramolecular polymers: from light-controlled small molecules to smart materials[J].Adv Mater,2023,35(10):e2204413.DOI: 10.1002/adma.202204413. [40] DevelL,CzarnyB,BeauF,et al.Third generation of matrix metalloprotease inhibitors: gain in selectivity by targeting the depth of the S1' cavity[J].Biochimie,2010,92(11):1501-1508.DOI: 10.1016/j.biochi.2010.07.017. [41] SchubertS,MarzloffG,RyderS,et al.Establishing a comprehensive wound care team and program[J].Phys Med Rehabil Clin N Am,2022,33(4):805-810.DOI: 10.1016/j.pmr.2022.06.006. [42] de AbreuVAC,PerdigãoJ,AlmeidaS.Metagenomic approaches to analyze antimicrobial resistance: an overview[J].Front Genet,2020,11:575592.DOI: 10.3389/fgene.2021.575592. [43] BrooksIR,SheriffA,MoranD,et al.Challenges of gene editing therapies for genodermatoses[J].Int J Mol Sci,2023,24(3):2298.DOI: 10.3390/ijms24032298. [44] 董凯旋,李云贵,罗浩天,等.混合现实技术在股前外侧皮瓣修复四肢软组织缺损中的临床应用[J].中华显微外科杂志,2023,46(5):534-539.DOI: 10.3760/cma.j.cn441206-20230411-00066. [45] MusuuzaJ,SutherlandBL,KurterS,et al.A systematic review of multidisciplinary teams to reduce major amputations for patients with diabetic foot ulcers[J].J Vasc Surg,2020,71(4):1433-1446.e3.DOI: 10.1016/j.jvs.2019.08.244. [46] 王丽薇,刘冰川,曲音音,等.多学科诊疗模式在慢性难愈合创面诊疗中的临床应用[J].北京大学学报(医学版),2025,57(1):185-191.DOI: 10.19723/j.issn.1671-167X.2025.01.028. [47] 周琴,王青,李双双,等.多专科综合干预在特重度烧伤患者整合治疗中的效果观察[J].中华烧伤杂志,2018,34(10):701-706.DOI: 10.3760/cma.j.issn.1009-2587.2018.10.010. [48] LavelleJ,SchastA,KerenR.Standardizing care processes and improving quality using pathways and continuous quality improvement[J].Curr Treat Options Peds,2015,1(4):347-358.DOI: 10.1007/s40746-015-0026-4. [49] MoningiS,PatkiA,PadhyN,et al.Enhanced recovery after surgery: an anesthesiologist's perspective[J].J Anaesthesiol Clin Pharmacol,2019,35(Suppl 1):S5-S13.DOI: 10.4103/joacp.JOACP_238_16. [50] MelnykM,CaseyRG,BlackP,et al.Enhanced recovery after surgery (ERAS) protocols: time to change practice?[J].Can Urol Assoc J,2011,5(5):342-348.DOI: 10.5489/cuaj.11002. -
Table 1. 正常创面愈合各阶段的具体过程和主要作用与机制
阶段与具体过程 主要作用 机制 关键信号/分子 细胞来源 主要调控机制 止血 血管收缩 减少局部血流 血清素、血栓素A2、内皮素-1、ADP 血小板、内皮细胞 神经-体液调节 血小板黏附与 聚集 形成血小板血栓 vWF、胶原蛋白、ADP、血栓素A2、血小板活化因子 血小板、内皮细胞 vWF/糖蛋白Ⅰb黏附、糖蛋白Ⅱb/Ⅲa激活 炎症 中性粒细胞浸润 清除细菌和坏死组织 IL-8、白三烯 B4、补体C5a、N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸、肿瘤坏死因子-α、IL-1β 中性粒细胞 趋化因子、Toll样受体/NOD样受体介导的炎症信号激活 巨噬细胞浸润与极化 调控炎症与组织修复 M1型巨噬细胞中内毒素/脂多糖、γ干扰素,M2型巨噬细胞中IL-4、IL-10、IL-13、TGF-β 单核细胞/巨噬细胞 细胞因子极化 淋巴细胞参与 介导适应性免疫 抗原、细胞因子（如γ干扰素、IL-2、IL-4、IL-17等） 淋巴细胞（T细胞、B细胞） 抗原提呈、T/B细胞活化 血管舒张与通透性增加 增加血流和血管通透性 组胺、缓激肽、一氧化氮、前列腺素E2、补体C3a与C5a 肥大细胞、内皮细胞、巨噬细胞、嗜碱性粒细胞 血管活性物质介导 增殖 ECM合成 构建肉芽组织,提供支架 PDGF、TGF-β、FGF（碱性FGF、酸性FGF）、EGF、KGF、骨形态发生蛋白 血小板、Fb、巨噬细胞、角质形成细胞、内皮细胞 TGF-β/Smad通路、丝裂原活化蛋白激酶通路激活及MMP/TIMP平衡 血管生成 形成新生血管,提供氧和营养 VEGF、Ang （Ang1与Ang2）、TGF-β、碱性FGF、PDGF、HIF-1α 内皮细胞、Fb、巨噬细胞、血小板 HIF-1α调控及VEGF/VEGF受体、Ang/Tie通路激活 Fb募集与增殖 合成ECM PDGF、TGF-β、FGF、EGF 血小板、巨噬细胞、Fb、内皮细胞 生长因子趋化与激活 上皮化 重建上皮屏障 EGF、TGF-α、KGF、肝细胞生长因子、TGF-β 角质形成细胞、Fb、巨噬细胞 EGF/EGF受体、TGF-β/Smad通路调节及细胞连接重建 肌Fb转化 产生收缩力 机械应力、TGF-β、PDGF、内皮素-1 Fb 机械张力、TGF-β/Smad通路调节 创面收缩 缩小创面面积 α-SMA、整合素、ECM连接蛋白（如纤维连接蛋白） 肌Fb α-SMA介导的细胞收缩 重塑 ECM重塑 提高组织强度和弹性 MMP（MMP-1、MMP-2、MMP-9等）、TIMP（TIMP-1、TIMP-2等）、TGF-β Fb、巨噬细胞、内皮细胞 MMP/TIMP平衡、力学应力调控 胶原成熟 提高组织抗张强度 TGF-β、LOX Fb TGF-β调控、LOX催化 注：ECM为细胞外基质,Fb为成纤维细胞,ADP为腺苷二磷酸,vWF为血管性血友病因子,IL为白细胞介素,TGF为转化生长因子,PDGF为血小板衍生生长因子,FGF为Fb生长因子,EGF为表皮生长因子,KGF为角质形成细胞生长因子,VEGF为血管内皮生长因子,Ang 为血管生成素,HIF-1α为缺氧诱导因子-1α,α-SMA为α-平滑肌肌动蛋白,MMP为基质金属蛋白酶,TIMP为组织金属蛋白酶抑制物,LOX为赖氨酰氧化酶,Tie为酪氨酸激酶受体 
下载: 导出CSV
-
下载:
图(1) / 表(1)
计量
- 文章访问数: 1884
- HTML全文浏览量: 43
- PDF下载量: 49
- 被引次数: 0
