Tissue Biology Research Unit, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Sci Adv. 2023 Oct 6;9(40):eadh1890. doi: 10.1126/sciadv.adh1890. Epub 2023 Oct 4.
Microtia is a congenital disorder that manifests as a malformation of the external ear leading to psychosocial problems in affected children. Here, we present a tissue-engineered treatment approach based on a bioprinted autologous auricular cartilage construct (EarCartilage) combined with a bioengineered human pigmented and prevascularized dermo-epidermal skin substitute (EarSkin) tested in immunocompromised rats. We confirmed that human-engineered blood capillaries of EarSkin connected to the recipient's vasculature within 1 week, enabling rapid blood perfusion and epidermal maturation. Bioengineered EarSkin displayed a stratified epidermis containing mature keratinocytes and melanocytes. The latter resided within the basal layer of the epidermis and efficiently restored the skin color. Further, in vivo tests demonstrated favorable mechanical stability of EarCartilage along with enhanced extracellular matrix deposition. In conclusion, EarCartilage combined with EarSkin represents a novel approach for the treatment of microtia with the potential to circumvent existing limitations and improve the aesthetic outcome of microtia reconstruction.
小耳畸形是一种先天性疾病,表现为外耳畸形,导致患病儿童出现社交心理问题。在这里,我们提出了一种基于生物打印自体耳软骨构建体(EarCartilage)和生物工程化的人类色素化和预血管化真皮-表皮皮肤替代物(EarSkin)的组织工程治疗方法,在免疫功能低下的大鼠中进行了测试。我们证实,EarSkin 的人工程化血管在 1 周内与受体的血管连接,从而实现了快速的血液灌注和表皮成熟。生物工程化的 EarSkin 显示出具有分层表皮的结构,其中包含成熟的角朊细胞和黑素细胞。后者位于表皮的基底层,并有效地恢复了皮肤颜色。此外,体内测试表明 EarCartilage 具有良好的机械稳定性,同时增强了细胞外基质的沉积。总之,EarCartilage 与 EarSkin 相结合代表了一种治疗小耳畸形的新方法,有可能克服现有局限性并改善小耳畸形重建的美学效果。