Acute cutaneous wounds treated with human decellularised dermis show enhanced angiogenesis during healing.

Acute cutaneous wounds treated with human decellularised dermis show enhanced angiogenesis during healing.
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DOI:
10.1371/journal.pone.0113209
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Bayat A
Bayat A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Greaves NS;Lqbal SA;Morris J;Benatar B;Alonso-Rasgado T;Baguneid M;Bayat A

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皮肤替代物在伤口愈合过程中对血管生成的影响尚不清楚。目的:比较自体、异体和异种皮肤替代物治疗的急性皮肤创面与二次创面愈合后的血管生成反应。在第0天,从50名健康志愿者(1-4点)采集4个5 mm的全层冲压活检组织。所有病例均以二次创面愈合(对照),二期植入胶原-GAG支架(CG),三期应用身体脱细胞真皮(DCD),切除的组织重新植入四期(自体移植)。根据研究组的分配,在第7天、第14天、第21天或第28天切除1-4部位的愈合组织。所有样本都被一分为二,其中一半用于组织学和免疫组织化学评估,而其余样本则从全基因组微阵列和突出显示的血管生成相关基因的qRT-PCR中提取RNA。所有创面在6周内使用激光多普勒成像和皮内分光光度分析进行连续成像。皮肤替代物之间固有的结构差异影响了再生真皮内毛细血管网络的分布和组织。DCD创面的血红蛋白流量(p=0.0035)、氧合血红蛋白浓度(p=0.0005)和免疫组织化学检测的血管数(p=0.046)在以后的时间点显著增加。这与膜型6基质金属蛋白酶(MT6-MMPs)(p=0.021)和原激动素2(prokineticin 2,PROK2)基因表达的增加(p=0.004)有关。来自侵入性和非侵入性方法的确证证据表明,DCD治疗导致创伤后血管生成增加。只有DCD组的促血管生成PROK2和细胞外基质蛋白MT6-MMPmRNA表达显著升高,这可能与观察到的反应有关。
The influence of skin substitutes upon angiogenesis during wound healing is unclear. To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention. On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4). In all cases, site 1 healed by secondary intention (control), site 2 was treated with collagen-GAG scaffold (CG), cadaveric decellularised dermis (DCD) was applied to site 3, whilst excised tissue was re-inserted into site 4 (autograft). Depending on study group allocation, healing tissue from sites 1-4 was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used in histological and immunohistochemical evaluation whilst extracted RNA from the remainder enabled whole genome microarrays and qRT-PCR of highlighted angiogenesis-related genes. All wounds were serially imaged over 6 weeks using laser-doppler imaging and spectrophotometric intracutaneous analysis. Inherent structural differences between skin substitutes influenced the distribution and organisation of capillary networks within regenerating dermis. Haemoglobin flux (p = 0.0035), oxyhaemoglobin concentration (p = 0.0005), and vessel number derived from CD31-based immunohistochemistry (p = 0.046) were significantly greater in DCD wounds at later time points. This correlated with time-matched increases in mRNA expression of membrane-type 6 matrix metalloproteinase (MT6-MMP) (p = 0.021) and prokineticin 2 (PROK2) (p = 0.004). Corroborating evidence from invasive and non-invasive modalities demonstrated that treatment with DCD resulted in increased angiogenesis after wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and extracellular matrix protease MT6-MMP seen only in the DCD group may contribute to observed responses.
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