生物材料递送生长因子调控创面修复的研究进展

翁婷婷; 蔡程浩; 韩春茂; 王新刚

doi:10.3760/cma.j.cn501225-20220430-00166

生物材料递送生长因子调控创面修复的研究进展

doi: 10.3760/cma.j.cn501225-20220430-00166

1.
浙江大学医学院第二临床学院，杭州　　310009
2.
浙江大学医学院附属第二医院烧伤　与创面修复科，杭州　　310009

基金项目:

国家重点研发计划 2016YFC1100803

国家自然科学基金面上项目 81772069

王正国创伤医学发展基金会生长因子复兴计划 SZYZ-TR-12

详细信息

通讯作者:
王新刚，Email：wangxingang8157@zju.edu.cn

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出版历程
- 收稿日期: 2022-04-30

Research advances on biomaterials for the delivery of growth factors to regulate wound repair

1.
The Second Clinical College, College of Medicine, Zhejiang University, Hangzhou 310009, China
2.
Department of Burn and Wound Repair, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China

Funds:

National Key Research and Development Program of China 2016YFC1100803

General Program of National Natural Science Foundation of China 81772069

Wang Zhengguo Foundation for Traumatic Medicine Growth Factor Rejuvenation Plan SZYZ-TR-12

More Information

Corresponding author: Wang Xingang, Email: wangxingang8157@zju.edu.cn

摘要

摘要: 创面修复是一个由多种细胞、细胞外基质、细胞因子等共同参与、高度协调又相互调控的复杂过程。多种生长因子在创面修复过程中发挥重要调控作用，而实现生长因子有效递送和功能持续发挥是至关重要的。近年来，生物材料在组织工程中的应用显示出巨大潜力，生物材料对生长因子的有效递送也日益受到关注。基于此，该文介绍了相关生长因子在创面修复过程中的作用机制，并重点讨论了生物材料递送生长因子加速创面愈合的最新进展，以期为临床上创面治疗提供新的启示。
- 伤口愈合 /
- 生物相容性材料 /
- 组织工程 /
- 皮肤 /
- 生长因子
Abstract: Wound repair is a highly coordinated and mutually regulated complex process involving various kinds of cells, extracellular matrices and cytokines. A variety of growth factors play an important regulatory role in wound healing, and it is critical to achieve effective delivery and sustained function of growth factors. In recent years, the application of biomaterials in tissue engineering has shown great potential, and the effective delivery of growth factors by biomaterials has attracted increasing attention. Based on this, this paper introduces the mechanism of related growth factors in the process of wound healing, focusing on the recent progress of biomaterial delivery of growth factors to accelerate wound healing, in order to provide new enlightenment for clinical wound treatment.
- Wound healing /
- Biocompatible materials /
- Tissue engineering /
- Skin /
- growth factors
所有作者均声明不存在利益冲突

HTML全文

表1 常见生长因子在创面修复中的作用及临床应用

生长因子名称	作用	实验动物创面	临床应用
bFGF	促进Fb、血管内皮细胞、平滑肌细胞增殖与分化；招募Fb向创面聚集，加速胶原蛋白的合成、分泌及沉积	糖尿病小鼠全层皮肤缺损创面、糖尿病后肢缺血模型小鼠创面	rb-FGF对烧伤、创伤及慢性溃疡等伤口均有明显促愈合作用
EGF	刺激内皮细胞、Fb、上皮细胞分裂增殖；促进创面血管生成及ECM合成	糖尿病小鼠全层皮肤缺损创面、小鼠全层皮肤缺损创面	重组人EGF能加快烧伤创面的愈合速度，缩短愈合时间
VEGF	促进内皮细胞的迁移、增殖和初级血管腔形成	糖尿病大鼠溃疡创面	重组人VEGF可促进创面新生血管形成、加速创面愈合
PDGF	促进巨噬细胞、Fb、血管内皮细胞及平滑肌细胞增殖和迁移；促进Fb增殖、合成ECM	糖尿病大鼠溃疡创面	重组PDGF可用于糖尿病溃疡治疗
TGF-β	TGF-β₁和TGF-β₂促进Fb向创面聚集，促进ECM形成，抑制基质金属蛋白酶生成；TGF-β₃抑制胶原蛋白生成	大鼠全层皮肤缺损创面	注射TGF-β可促进关节软骨缺损修复
IGF-Ⅰ	触发Fb增殖，促进ECM的合成和分泌；促进角质细胞的迁移及细胞有丝分裂，有利于创面再上皮化	小鼠全层皮肤缺损创面	局部注射IGF-Ⅰ可促进全层皮肤缺损创面愈合
注：bFGF为碱性成纤维细胞生长因子，EGF为表皮生长因子，VEGF为血管内皮生长因子，PDGF为血小板衍生生长因子，TGF为转化生长因子，IGF-Ⅰ为胰岛素样生长因子Ⅰ，Fb为成纤维细胞，ECM为细胞外基质，rb-FGF为重组牛bFGF

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表2 不同递送系统的生物材料比较

生物材料	负载的生物活性因子	优点	不足
可降解聚合物，例如纳米纤维、微球、支架、水凝胶等	VEGF、bFGF、PDGF、EGF、TGF-β	通用降解动力学、药物控释特性、提供的乳酸盐副产物可促进创面愈合	酸性副产物可造成创面周围组织损伤
阳离子聚合物	VEGF质粒、PDGF质粒	在创面表面的生物黏附性良好	因具有细胞毒性而受到剂量限制
脂质体	bFGF、KGF、VEGF质粒、PDGF质粒、促血管生成素-1质粒	出色的皮肤渗透能力、与药物的强疏水相互作用、脂质体膜易行表面修饰、成分与皮肤相似可增加停留时间	使用有机溶剂时易存在形成颗粒、药物渗漏、聚结等问题
注：VEGF为血管内皮生长因子，bFGF为碱性成纤维细胞生长因子，PDGF为血小板衍生生长因子，EGF为表皮生长因子，TGF为转化生长因子，KGF为角质形成细胞生长因子

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《中华烧伤与创面修复杂志》第六届编辑委员会通讯编委名单按姓氏拼音排序

贲道锋	卞徽宁	曹永倩	晁生武	陈辉	陈婧	陈朗	陈铭锐	陈鹏	陈晓东
陈忠勇	程君涛	迟云飞	储国平	党永明	邓呈亮	狄海萍	丁国兵	丁若虹	董茂龙
段红杰	段鹏	樊东力	房贺	冯光	付忠华	郭毅斌	韩兆峰	侯春胜	胡德林
胡炯宇	胡骁骅	胡晓燕	黄红军	纪世召	江华	姜丽萍	姜玉峰	雷娜	黎宁
李东杰	李峰	李靖	李晓东	李晓鲁	梁钢	梁鹏飞	林才	林国安	林源
刘德伍	刘健	刘军	刘淑华	龙奕	卢长虹	鲁峰	吕开阳	吕强	马思远
牛轶雯	欧阳军	乔亮	覃凤均	邱学文	曲滨	任超	沈江涌	石继红	宋慧锋
苏海涛	苏永涛	孙勇	孙瑜	谭江琳	唐修俊	滕苗	田社民	涂家金	汪虹
汪洋	王爱萍	王德怀	王洪涛	王会军	王良喜	王爽	王献珍	王志永	温冰
邬佳敏	吴红	吴继炎	吴巍巍	吴祖煌	向飞	向军	谢举临	谢松涛	辛海明
许喜生	许学文	薛斌	杨建民	杨敏烈	杨薛康	姚明	姚兴伟	叶祥柏	易成刚
易南	于东宁	岳丽青	翟红军	詹日兴	张博	张东霞	张红艳	张菊芳	张玲娟
张庆红	张彦琦	张寅	张元海	张志	赵全	赵冉	赵雄	郑德义	郑东风
郑军	周国富	周俊峄	周琴	周万芳	朱峰	朱宇刚	祝筱梅	邹立津	邹晓防

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参考文献(42)

[1]	韩春茂, 余美荣, 王新刚. 创面处理主要进展概述[J]. 中华烧伤杂志, 2018,34(12):864-867.DOI: 10.3760/cma.j.issn.1009-2587.2018.12.009.
[2]	NiuY, LiQ, DingY, et al. Engineered delivery strategies for enhanced control of growth factor activities in wound healing[J]. Adv Drug Deliv Rev, 2019,146:190-208.DOI: 10.1016/j.addr.2018.06.002.
[3]	TakeoM, LeeW, ItoM. Wound healing and skin regeneration[J]. Cold Spring Harb Perspect Med, 2015,5(1):a23267.DOI: 10.1101/cshperspect.a023267.
[4]	ZubairM, AhmadJ. Role of growth factors and cytokines in diabetic foot ulcer healing: a detailed review[J]. Rev Endocr Metab Disord, 2019,20(2):207-217.DOI: 10.1007/s11154-019-09492-1.
[5]	XiongS, ZhangX, LuP, et al. A Gelatin-sulfonated silk composite scaffold based on 3D printing technology enhances skin regeneration by stimulating epidermal growth and dermal neovascularization[J]. Sci Rep, 2017,7(1):4288.DOI: 10.1038/s41598-017-04149-y.
[6]	FuX, ShenZ, ChenY, et al. Randomised placebo-controlled trial of use of topical recombinant bovine basic fibroblast growth factor for second-degree burns[J]. Lancet, 1998,352(9141):1661-1664.DOI: 10.1016/S0140-6736(98)01260-4.
[7]	JohnsonKE, WilgusTA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair[J]. Adv Wound Care (New Rochelle), 2014,3(10):647-661.DOI: 10.1089/wound.2013.0517.
[8]	ShenS, WangF, FernandezA, et al. Role of platelet-derived growth factor in type Ⅱ diabetes mellitus and its complications[J]. Diab Vasc Dis Res, 2020,17(7):1479164120942119.DOI: 10.1177/1479164120942119.
[9]	LichtmanMK, Otero-VinasM, FalangaV. Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis[J]. Wound Repair Regen, 2016,24(2):215-222.DOI: 10.1111/wrr.12398.
[10]	KhanI, RahmanS U, TangE, et al. Accelerated burn wound healing with photobiomodulation therapy involves activation of endogenous latent TGF-β1[J]. Sci Rep, 2021,11(1):13371.DOI: 10.1038/s41598-021-92650-w.
[11]	HimpeE, KooijmanR. Insulin-like growth factor-I receptor signal transduction and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway[J]. Biofactors, 2009,35(1):76-81.DOI: 10.1002/biof.20.
[12]	DasS, SinghG, MajidM, et al. Syndesome therapeutics for enhancing diabetic wound healing[J]. Adv Healthc Mater, 2016,5(17):2248-2260.DOI: 10.1002/adhm.201600285.
[13]	IsnerJM, PieczekA, SchainfeldR, et al. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb[J]. Lancet, 1996,348(9024):370-374.DOI: 10.1016/s0140-6736(96)03361-2.
[14]	SteedDL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. Diabetic Ulcer Study Group[J]. J Vasc Surg, 1995,21(1):71-78;discussion 79-81.DOI: 10.1016/s0741-5214(95)70245-8.
[15]	石宗义. 转化生长因子β1促进关节软骨缺损修复的临床应用[J]. 中国现代医药杂志, 2006,8(7):37-39. DOI: 10.3969/j.issn.1672-9463.2006.07.016.
[16]	EmmersonE, CampbellL, DaviesF C, et al. Insulin-like growth factor-1 promotes wound healing in estrogen-deprived mice: new insights into cutaneous IGF-1R/ERα cross talk[J]. J Invest Dermatol, 2012,132(12):2838-2848.DOI: 10.1038/jid.2012.228.
[17]	BerthetM, GauthierY, LacroixC, et al. Nanoparticle-based dressing: the future of wound treatment?: (Trends in Biotechnology 35, 770-784, 2017)[J]. Trends Biotechnol, 2018,36(1):119.DOI: 10.1016/j.tibtech.2017.08.007.
[18]	DesmetCM, PréatV, GallezB. Nanomedicines and gene therapy for the delivery of growth factors to improve perfusion and oxygenation in wound healing[J]. Adv Drug Deliv Rev, 2018,129:262-284.DOI: 10.1016/j.addr.2018.02.001.
[19]	ReckhenrichAK, HopfnerU, KrötzF, et al. Bioactivation of dermal scaffolds with a non-viral copolymer-protected gene vector[J]. Biomaterials, 2011,32(7):1996-2003.DOI: 10.1016/j.biomaterials.2010.11.022.
[20]	McKnightCD, WinnSR, GongX, et al. Revascularization of rat fasciocutaneous flap using CROSSEAL with VEGF protein or plasmid DNA expressing VEGF[J]. Otolaryngol Head Neck Surg, 2008,139(2):245-249.DOI: 10.1016/j.otohns.2008.04.014.
[21]	JeschkeMG, KleinD. Liposomal gene transfer of multiple genes is more effective than gene transfer of a single gene[J]. Gene Ther, 2004,11(10):847-855.DOI: 10.1038/sj.gt.3302229.
[22]	ChereddyKK, LopesA, KoussoroplisS, et al. Combined effects of PLGA and vascular endothelial growth factor promote the healing of non-diabetic and diabetic wounds[J]. Nanomedicine, 2015,11(8):1975-1984.DOI: 10.1016/j.nano.2015.07.006.
[23]	GuoR, XuS, MaL, et al. The healing of full-thickness burns treated by using plasmid DNA encoding VEGF-165 activated collagen-chitosan dermal equivalents[J]. Biomaterials, 2011,32(4):1019-1031.DOI: 10.1016/j.biomaterials.2010.08.087.
[24]	O'DwyerJ, CullenM, FattahS, et al. Development of a sustained release nano-in-gel delivery system for the chemotactic and angiogenic growth factor stromal-derived factor 1α[J]. Pharmaceutics, 2020,12(6):513.DOI: 10.3390/pharmaceutics12060513.
[25]	ImGB, KimYH, KimYJ, et al. Enhancing the wound healing effect of conditioned medium collected from mesenchymal stem cells with high passage number using bioreducible nanoparticles[J]. Int J Mol Sci, 2019,20(19).DOI: 10.3390/ijms20194835.
[26]	LaiHJ, KuanCH, WuHC, et al. Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing[J]. Acta Biomater, 2014,10(10):4156-4166.DOI: 10.1016/j.actbio.2014.05.001.
[27]	MariiaK, ArifM, ShiJ, et al. Novel chitosan-ulvan hydrogel reinforcement by cellulose nanocrystals with epidermal growth factor for enhanced wound healing: In vitro and in vivo analysis[J]. Int J Biol Macromol, 2021,183:435-446.DOI: 10.1016/j.ijbiomac.2021.04.156.
[28]	LeeYH, HongYL, WuTL. Novel silver and nanoparticle- encapsulated growth factor co-loaded chitosan composite hydrogel with sustained antimicrobility and promoted biological properties for diabetic wound healing[J]. Mater Sci Eng C Mater Biol Appl, 2021,118:111385.DOI: 10.1016/j.msec.2020.111385.
[29]	HajimiriM, ShahverdiS, EsfandiariMA, et al. Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing[J]. Drug Dev Ind Pharm, 2016,42(5):707-719.DOI: 10.3109/03639045.2015.1075030.
[30]	XiaG, LiuY, TianM, et al. Nanoparticles/thermosensitive hydrogel reinforced with chitin whiskers as a wound dressing for treating chronic wounds[J]. J Mater Chem B, 2017,5(17):3172-3185.DOI: 10.1039/c7tb00479f.
[31]	LosiP, BrigantiE, ErricoC, et al. Fibrin-based scaffold incorporating VEGF- and bFGF-loaded nanoparticles stimulates wound healing in diabetic mice[J]. Acta Biomater, 2013,9(8):7814-7821.DOI: 10.1016/j.actbio.2013.04.019.
[32]	TokatlianT, CamC, SeguraT. Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model[J]. Adv Healthc Mater, 2015,4(7):1084-1091.DOI: 10.1002/adhm.201400783.
[33]	TanhaS, Rafiee-TehraniM, AbdollahiM, et al. G-CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo[J]. J Biomed Mater Res A, 2017,105(10):2830-2842.DOI: 10.1002/jbm.a.36135.
[34]	ZhuK, WuM, LaiH, et al. Nanoparticle-enhanced generation of gene-transfected mesenchymal stem cells for in vivo cardiac repair[J]. Biomaterials, 2016,74:188-199.DOI: 10.1016/j.biomaterials.2015.10.010.
[35]	LiM, QiuL, HuW, et al. Genetically-modified bone mesenchymal stem cells with TGF-β3 improve wound healing and reduce scar tissue formation in a rabbit model[J]. Exp Cell Res, 2018,367(1):24-29.DOI: 10.1016/j.yexcr.2018.02.006.
[36]	LiS, TangQ, XuH, et al. Improved stability of KGF by conjugation with gold nanoparticles for diabetic wound therapy[J]. Nanomedicine (Lond), 2019,14(22):2909-2923.DOI: 10.2217/nnm-2018-0487.
[37]	PanA, ZhongM, WuH, et al. Topical application of keratinocyte growth factor conjugated gold nanoparticles accelerate wound healing[J]. Nanomedicine, 2018,14(5):1619-1628.DOI: 10.1016/j.nano.2018.04.007.
[38]	LeeYH, LinSJ. Chitosan/PVA hetero-composite hydrogel containing antimicrobials, perfluorocarbon nanoemulsions, and growth factor-loaded nanoparticles as a multifunctional dressing for diabetic wound healing: synthesis, characterization, and in vitro/in vivo evaluation[J]. Pharmaceutics, 2022,14(3).DOI: 10.3390/pharmaceutics14030537.
[39]	XieZ, ParasCB, WengH, et al. Dual growth factor releasing multi-functional nanofibers for wound healing[J]. Acta Biomater, 2013,9(12):9351-9359.DOI: 10.1016/j.actbio.2013.07.030.
[40]	ChengB, JiangY, FuX, et al. Epidemiological characteristics and clinical analyses of chronic cutaneous wounds of inpatients in China: prevention and control[J]. Wound Repair Regen, 2020,28(5):623-630.DOI: 10.1111/wrr.12825.
[41]	YangY, XiaT, ChenF, et al. Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats[J]. Mol Pharm, 2012,9(1):48-58.DOI: 10.1021/mp200246b.
[42]	VeithA P, HendersonK, SpencerA, et al. Therapeutic strategies for enhancing angiogenesis in wound healing[J]. Adv Drug Deliv Rev, 2019,146:97-125.DOI: 10.1016/j.addr.2018.09.010.