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使用纤维蛋白水凝胶递送磺胺嘧啶银和脂肪来源干细胞可改善感染性烧伤创面的再生。

Delivery of silver sulfadiazine and adipose derived stem cells using fibrin hydrogel improves infected burn wound regeneration.

机构信息

Combat Trauma and Burn Injury Research, US Army Institute of Surgical Research, Ft. Sam Houston, TX, United States of America.

出版信息

PLoS One. 2019 Jun 13;14(6):e0217965. doi: 10.1371/journal.pone.0217965. eCollection 2019.


DOI:10.1371/journal.pone.0217965
PMID:31194776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6563979/
Abstract

Infection control is necessary for improved burn wound regeneration. In this study contact burn wounds were induced on the dorsum of the rats and were infected with Pseudomonas aeruginosa (107cfu/ml of saline) and left overnight (12-14 hours) to establish the infection. After 12 hours, the wounds were treated with PEGylated fibrin hydrogel containing 50 mgs of silver sulfadiazine (SSD) loaded chitosan microsphere (SSD-CSM-FPEG). On day 9, SSD-CSM-FPEG treated burn wounds further received adipose derived stem cell (5×104 ASCs cells/ml) embedded in PEGylated fibrin hydrogel. Wounds were assessed for the healing outcomes such as neovascularization, granulation tissue formation, wound closure and collagen maturation. Analysis of bacterial load in the burn wound biopsies, demonstrated that SSD-CSM-FPEG significantly reduced bacterial infection, while overt infection was still observed in the untreated groups on day 14. Sequential treatment of infected wounds with SSD-CSM-FPEG followed by ASC-FPEGs (SSD-CSM-ASC-FPEG) significantly reduced bacterial colonization (9 log reduction) and pro-inflammatory cytokine (TNF-α) expression. A significant increase in neovascularization markers; NG2 and vWF was also observed. Histological analysis indicated the wounds treated with SSD-CSM-ASC-FPEG increased amount of dermal collagen matrix deposition, a thicker granulation tissue on day 21 and more mature collagen on day 28. This work demonstrates that the sequential treatment of infected burn wounds with SSD-CSM-FPEG followed by ASC-FPEG reduces bacterial infection as well as promotes neo-vascularization with improved matrix remodeling.

摘要

感染控制对于改善烧伤创面再生是必要的。在这项研究中,在大鼠背部造成接触性烧伤创面,并感染铜绿假单胞菌(107cfu/ml 生理盐水),过夜(12-14 小时)以建立感染。12 小时后,用载有磺胺嘧啶银(SSD)的壳聚糖微球(SSD-CSM)的聚乙二醇化纤维蛋白水凝胶(PEGylated fibrin hydrogel)处理创面。第 9 天,SSD-CSM-FPEG 处理的烧伤创面进一步接受负载脂肪源性干细胞(5×104 ASCs 细胞/ml)的聚乙二醇化纤维蛋白水凝胶。通过新生血管形成、肉芽组织形成、创面闭合和胶原成熟等愈合结果评估创面。对烧伤创面活检中的细菌负荷进行分析,结果表明 SSD-CSM-FPEG 显著减少了细菌感染,而未处理组在第 14 天仍观察到明显的感染。用 SSD-CSM-FPEG 对感染创面进行序贯治疗,然后用 ASC-FPEG 治疗(SSD-CSM-ASC-FPEG),可显著减少细菌定植(减少 9 个对数)和促炎细胞因子(TNF-α)的表达。还观察到新生血管化标志物 NG2 和 vWF 的显著增加。组织学分析表明,用 SSD-CSM-ASC-FPEG 治疗的创面在第 21 天增加了真皮胶原基质的沉积量,在第 28 天有更厚的肉芽组织和更成熟的胶原。这项工作表明,用 SSD-CSM-FPEG 对感染性烧伤创面进行序贯治疗,然后用 ASC-FPEG 治疗,可以减少细菌感染,促进新生血管形成,并改善基质重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/60c3a03c2713/pone.0217965.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/954077cfbacd/pone.0217965.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/9ea3e94b77f9/pone.0217965.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/cc5cf486bd10/pone.0217965.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/992a292bd070/pone.0217965.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/430be57a7d7b/pone.0217965.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/32546217170c/pone.0217965.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/3682d615f693/pone.0217965.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/4c75b9749474/pone.0217965.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/60c3a03c2713/pone.0217965.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/954077cfbacd/pone.0217965.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/9ea3e94b77f9/pone.0217965.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/cc5cf486bd10/pone.0217965.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/992a292bd070/pone.0217965.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/430be57a7d7b/pone.0217965.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/32546217170c/pone.0217965.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/3682d615f693/pone.0217965.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/4c75b9749474/pone.0217965.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c24/6563979/60c3a03c2713/pone.0217965.g009.jpg

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本文引用的文献

[1]
5-HT1A Receptor Function Makes Wound Healing a Happier Process.

Front Pharmacol. 2018-12-11

[2]
Delivery of Allogeneic Adipose Stem Cells in Polyethylene Glycol-Fibrin Hydrogels as an Adjunct to Meshed Autografts After Sharp Debridement of Deep Partial Thickness Burns.

Stem Cells Transl Med. 2018-2-18

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Neuroscience. 2017-9-19

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A PEGylated fibrin hydrogel-based antimicrobial wound dressing controls infection without impeding wound healing.

Int Wound J. 2017-8-2

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