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皮肤工程学II:在一种新的猪模型中移植大规模实验室培养的皮肤类似物

Skingineering II: transplantation of large-scale laboratory-grown skin analogues in a new pig model.

作者信息

Schiestl Clemens, Biedermann Thomas, Braziulis Erik, Hartmann-Fritsch Fabienne, Böttcher-Haberzeth Sophie, Arras Margarete, Cesarovic Nikola, Nicolls Flora, Linti Carsten, Reichmann Ernst, Meuli Martin

机构信息

Pediatric Burn Center, Plastic and Reconstructive Surgery, Department of Surgery, University Children's Hospital, Steinwiesstrasse 75, Zurich, Switzerland.

出版信息

Pediatr Surg Int. 2011 Mar;27(3):249-54. doi: 10.1007/s00383-010-2792-1.

DOI:10.1007/s00383-010-2792-1
PMID:21069348
Abstract

BACKGROUND

Tissue engineering of skin with near-normal anatomy is an intriguing novel strategy to attack the still unsolved problem of how to ideally cover massive full-thickness skin defects. After successful production of large, pig cell-derived skin analogues, we now aim at developing an appropriate large animal model for transplantation studies.

MATERIALS AND METHODS

In four adult Swiss pigs, full-thickness skin defects, measuring 7.5 × 7.5 cm, were surgically created and then shielded against the surrounding skin by a new, self-designed silicone chamber. In two animals each, Integra dermal regeneration templates or cultured autologous skin analogues, respectively, were applied onto the wound bed. A sophisticated shock-absorbing dressing was applied for the ensuing 3 weeks. Results were documented photographically and histologically.

RESULTS

All animals survived uneventfully. Integra healed in perfectly, while the dermo-epidermal skin analogues showed complete take of the dermal compartment but spots of missing epidermis. The chamber proved effective in precluding ("false positive") healing from the wound edges and the special dressing efficiently kept the operation site intact and clean for the planned 3 weeks.

CONCLUSION

We present a novel and valid pig model permitting both transplantation of large autologous, laboratory-engineered skin analogues and also keeping the site of intervention undisturbed for at least three postoperative weeks. Hence, the model will be used for experiments testing whether such large skin analogues can restore near-normal skin, particularly in the long term. If so, clinical application can be envisioned.

摘要

背景

构建具有接近正常解剖结构的皮肤组织工程是一种引人关注的新策略,旨在攻克如何理想地覆盖大面积全层皮肤缺损这一尚未解决的问题。在成功制备出大型猪细胞源皮肤替代物后,我们现在致力于开发一种适用于移植研究的大型动物模型。

材料与方法

对4只成年瑞士猪进行手术,制造出面积为7.5×7.5厘米的全层皮肤缺损,然后用一种新的自行设计的硅胶室将伤口与周围皮肤隔开。在每两只动物中,分别将Integra真皮再生模板或培养的自体皮肤替代物应用于创面。在接下来的3周内使用一种精密的减震敷料。通过拍照和组织学方法记录结果。

结果

所有动物均顺利存活。Integra完美愈合,而真皮 - 表皮皮肤替代物的真皮部分完全成活,但有表皮缺失的斑点。该硅胶室被证明能有效防止伤口边缘的(“假阳性”)愈合,并且这种特殊敷料在计划的3周内有效地保持了手术部位的完整和清洁。

结论

我们提出了一种新颖且有效的猪模型,既允许移植大型自体实验室工程皮肤替代物,又能使干预部位在术后至少三周内不受干扰。因此,该模型将用于测试这种大型皮肤替代物是否能恢复接近正常的皮肤,特别是从长期来看。如果可以,那么就可以设想其临床应用。

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本文引用的文献

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Skingineering I: engineering porcine dermo-epidermal skin analogues for autologous transplantation in a large animal model.皮肤工程学I:构建用于大型动物模型自体移植的猪真皮-表皮皮肤类似物
Pediatr Surg Int. 2011 Mar;27(3):241-7. doi: 10.1007/s00383-010-2777-0.
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Human eccrine sweat gland cells can reconstitute a stratified epidermis.人汗腺细胞可重建成层状表皮。
J Invest Dermatol. 2010 Aug;130(8):1996-2009. doi: 10.1038/jid.2010.83. Epub 2010 Apr 8.
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Tissue engineering of skin.皮肤的组织工程。
儿童培养自体真皮-表皮皮肤替代物的长期结果:一项I期临床试验的5年结果
J Burn Care Res. 2025 Mar 4;46(2):326-334. doi: 10.1093/jbcr/irae150.
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Evaluation of secretomes derived from human dermal and adipose tissue mesenchymal stem/stromal cells for skin wound healing: not as effective as cells.评估人真皮和脂肪组织间充质干细胞分泌组在皮肤伤口愈合中的作用:不如细胞有效。
Stem Cell Res Ther. 2024 Jan 17;15(1):15. doi: 10.1186/s13287-023-03630-y.
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Combining bioengineered human skin with bioprinted cartilage for ear reconstruction.将生物工程化的人类皮肤与生物打印软骨相结合,用于耳朵重建。
Sci Adv. 2023 Oct 6;9(40):eadh1890. doi: 10.1126/sciadv.adh1890. Epub 2023 Oct 4.
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Induction of angiogenic and inflammation-associated dermal biomarkers following acute UVB exposure on bio-engineered pigmented dermo-epidermal skin substitutes in vivo.急性紫外线B照射后,生物工程化色素沉着真皮-表皮皮肤替代物在体内诱导血管生成和炎症相关的皮肤生物标志物。
Pediatr Surg Int. 2019 Jan;35(1):129-136. doi: 10.1007/s00383-018-4384-4. Epub 2018 Nov 14.
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Skin-Derived Stem Cells for Wound Treatment Using Cultured Epidermal Autografts: Clinical Applications and Challenges.使用培养的自体表皮移植的皮肤来源干细胞用于伤口治疗:临床应用与挑战
Stem Cells Int. 2018 Mar 25;2018:4623615. doi: 10.1155/2018/4623615. eCollection 2018.
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Skin Tissue Engineering: Application of Adipose-Derived Stem Cells.皮肤组织工程:脂肪来源干细胞的应用
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Transglutaminases, involucrin, and loricrin as markers of epidermal differentiation in skin substitutes derived from human sweat gland cells.转谷氨酰胺酶、内披蛋白和兜甲蛋白作为源自人汗腺细胞的皮肤替代物中表皮分化的标志物。
Pediatr Surg Int. 2010 Jan;26(1):71-7. doi: 10.1007/s00383-009-2517-5.
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Porcine wound healing in full-thickness skin defects using Integra™ with and without fibrin glue with keratinocytes.使用Integra™并添加或不添加纤维蛋白胶与角质形成细胞治疗猪全层皮肤缺损的伤口愈合情况。
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Use of a novel porcine collagen paste as a dermal substitute in full-thickness wounds.使用新型猪胶原蛋白糊剂作为全层伤口的真皮替代物。
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Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring.人类纤维增生性瘢痕的雌性杜洛克/约克夏猪模型综述。
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The co-application of sprayed cultured autologous keratinocytes and autologous fibrin sealant in a porcine wound model.在猪伤口模型中联合应用喷洒培养的自体角质形成细胞和自体纤维蛋白封闭剂。
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Reconstructive surgery with a dermal regeneration template: clinical and histologic study.使用真皮再生模板的重建手术:临床与组织学研究
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