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缓释血小板衍生生长因子和转化生长因子-β对环磷酰胺诱导的伤口愈合受损的影响。

Effect of sustained-release PDGF and TGF-beta on cyclophosphamide-induced impaired wound healing.

作者信息

Ashraf Azra, Lee Peter H U, Kim Kyoung, Zaporojan Victor, Bonassar Lawrence, Valentini Robert, Spangenberger Anthony, Weinzweig Jeffrey

机构信息

Chicago, Ill.; Boston and Worcester, Mass.; Los Angeles, Calif.; Ithaca, N.Y.; and Providence, R.I. From the Craniofacial Biology and Tissue Engineering Laboratory, Chicago Center for Plastic and Reconstructive Surgery, the Caritas Saint Elizabeth's Medical Center, Department of General Surgery, Tufts University Medical School, the Department of Biomedical Engineering and Mechanical and Aerospace Engineering, Cornell University, the University of Massachusetts Medical School, Center for Tissue Engineering, and Myomics.

出版信息

Plast Reconstr Surg. 2009 Oct;124(4):1118-1124. doi: 10.1097/PRS.0b013e3181b5a349.

Abstract

BACKGROUND

Proper wound healing is pivotal to successful surgical outcomes. Previous studies have shown that growth factors can be used to enhance tissue repair under impaired healing conditions. However, because of limited delivery methods, the growth factors in these studies were delivered either topically or as a single local administration.

METHODS

Sixty Sprague-Dawley rats were divided equally into five groups and served as untreated normal controls or were implanted subcutaneously with a novel sustained-release drug delivery system through a dorsal incisional wound. This system delivered either transforming growth factor (TGF)-beta alone, platelet-derived growth factor (PDGF) alone, or TGF-beta and PDGF in combination, or served as unloaded sham controls. Wound healing was impaired in all treated rats by the administration of cyclophosphamide on days 1, 3, and 5. Wound tensile breaking strength was determined on days 4, 7, and 14.

RESULTS

Sustained release of either TGF-beta or PDGF alone not only failed to improve the healing of cyclophosphamide-induced impaired wound healing but resulted in a paradoxical decrease in wound tensile breaking strength by day 7. However, the combined delivery of both TGF-beta and PDGF improved wound healing and significantly increased wound tensile breaking strength by day 7.

CONCLUSIONS

Sustained-release delivery of TGF-beta and PDGF in combination, but not separately, by a subcutaneously implanted drug delivery system significantly improves cyclophosphamide-induced impaired wound healing in rats.

摘要

背景

恰当的伤口愈合对于手术成功至关重要。以往研究表明,生长因子可用于在愈合受损的情况下促进组织修复。然而,由于递送方法有限,这些研究中的生长因子要么是局部递送,要么是单次局部给药。

方法

将60只Sprague-Dawley大鼠平均分为五组,分别作为未处理的正常对照组,或通过背部切口伤口皮下植入新型缓释药物递送系统。该系统单独递送转化生长因子(TGF)-β、单独递送血小板衍生生长因子(PDGF),或联合递送TGF-β和PDGF,或作为未装载药物的假手术对照组。在第1、3和5天给予环磷酰胺,使所有处理组大鼠的伤口愈合受损。在第4、7和14天测定伤口抗张断裂强度。

结果

单独持续释放TGF-β或PDGF不仅未能改善环磷酰胺诱导的伤口愈合受损情况,反而在第7天时导致伤口抗张断裂强度出现反常下降。然而,联合递送TGF-β和PDGF可改善伤口愈合,并在第7天时显著提高伤口抗张断裂强度。

结论

通过皮下植入药物递送系统联合(而非单独)持续释放TGF-β和PDGF可显著改善环磷酰胺诱导的大鼠伤口愈合受损情况。

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