Modulation of scar tissue formation using different dermal regeneration templates in the treatment of experimental full-thickness wounds

Modulation of scar tissue formation using different dermal regeneration templates in the treatment of experimental full-thickness wounds
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DOI:
10.1111/j.1067-1927.2004.012504.x
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发表时间:
2004-09-01
影响因子:
2.9
通讯作者:
Steinstraesser, L
Steinstraesser, L
中科院分区:
医学3区
文献类型:
--
作者:
Druecke, D;Lamme, EN;Steinstraesser, L

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皮肤功能的恢复是每位烧伤外科医生追求的目标。全层皮肤缺损的劈裂皮移植治疗导致瘢痕形成,这通常是脆弱和不稳定的。因此,本研究的目的是分析使用临床可用的生物聚合物真皮再生模板治疗的急性全层伤口中的伤口愈合和瘢痕组织形成。Gottingen小型猪(n= 3)两侧胁腹的全层伤口(3 x 3 cm)单独使用断层皮肤移植物或与1-乙基-3-(3-二甲基氨基丙基)-碳二亚胺(EDC)交联胶原支架、Integra或聚乙二醇己二酸酯-聚对苯二甲酸丁二醇酯(PEGT/PBT)支架联合使用。每周检查伤口(每组n= 12),持续六周,以评估移植物的吸收、收缩(面积测量)和外观。一周和六周后采集的组织学样本用于评估支架血管生成、生物相容性和瘢痕组织质量。在所有伤口中,伤后一周的移植物吸收率在93%到100%之间。对照伤口,用分裂皮肤移植物治疗,显示很少肉芽组织形成,而EDC-胶原蛋白治疗的伤口显示两到三倍的肉芽组织形成。胶原支架在一周内完全降解。Integra和PEGT/PBT支架仅通过支架的三分之二显示血管生成,这导致表皮完整性的丧失。只有基底细胞存活,增殖,并在三周内再生一个完全分化的表皮。肉芽厚度与胶原支架治疗的伤口相当。六周后,对照伤口显示伤口收缩率为27.2 +/-6.1%,Integra治疗伤口为34.6 +/-6.4%,胶原支架治疗伤口为38.1 +/-5.0%,PEGT/PBT支架治疗伤口为54.5 +/-3.9%。后一组伤口的收缩明显大于其他治疗组的伤口。在显微镜下,对照和胶原支架处理的伤口显示未成熟的瘢痕组织,其在EDC-胶原处理的伤口中厚两倍。Integra治疗的伤口显示出未降解的胶原支架纤维,部分新生真皮组织形成,部分区域有巨细胞和其他炎性细胞。PEGT/PBT支架几乎完全降解。支架颗粒被巨噬细胞团吞噬并在细胞内降解。瘢痕组织处于ECM重塑的早期阶段。总之,本研究表明,真皮组织形成和瘢痕形成的速率受到支架材料诱导的支架血管生成、降解和宿主反应速率的影响。
The recovery of skin function is the goal of each burn surgeon. Split-skin graft treatment of full-thickness skin defects leads to scar formation, which is often vulnerable and instable. Therefore, the aim of this study was to analyze wound healing and scar tissue formation in acute full-thickness wounds treated with clinically available biopolymer dermal regeneration templates. Full-thickness wounds (3 x 3 cm) on both flanks of Gottingen mini pigs (n= 3) were treated with split-thickness skin graft alone or in combination with a 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) cross-linked-collagen scaffold, Integra, or a polyethyleneglycol terephthalate-polybutylene terephthalate (PEGT/PBT) scaffold. The wounds (n= 12 per group) were examined weekly for six weeks to evaluate graft take, contraction (planimetry), and cosmetic appearance. Histologic samples taken after one and six weeks were used to assess scaffold angiogenesis, biocompatibility, and scar tissue quality. In all wounds, one week postwounding graft take was between 93 and 100 percent. The control wound, treated with split-skin graft, showed little granulation tissue formation, whereas the EDC-collagen treated wounds showed two to three times more granulation tissue formation. The collagen scaffold was completely degraded within one week. The Integra and PEGT/PBT scaffolds showed angiogenesis only through two-thirds of the scaffold, which resulted in loss of integrity of the epidermis. Only basal cells survived, proliferated, and regenerated a fully differentiated epidermis within three weeks. Granulation thickness was comparable to collagen scaffold-treated wounds. After six weeks, control wounds showed a wound contraction of 27.2 +/- 6.1 percent, Integra-treated wounds 34.6 +/- 6.4 percent, collagen scaffold-treated wounds 38.1 +/- 5.0 percent, and PEGT/PBT scaffold-treated wounds 54.5 +/- 3.9 percent. The latter wounds had significantly more contraction than wounds of other treatment groups. Microscopically, the control and collagen scaffold-treated wounds showed an immature scar tissue that was two times thicker in the EDC-collagen treated wounds. The Integra-treated wounds showed nondegraded collagen scaffold fibers with partly de novo dermal tissue formation and partly areas with giant cells and other inflammatory cells. The PEGT/PBT scaffold was almost completely degraded. Scaffold particles were phagocytosized and degraded intracellularly by clusters of macrophages. The scar tissue was in the early phase of ECM remodeling. In conclusion, this study showed that the rate of dermal tissue formation and scarring is influenced by the rate of scaffold angiogenesis, degradation, and host response induced by the scaffold materials.