Gvaramia David, Fisch Philipp, Flégeau Killian, Huber Lena, Kern Johann, Jakob Yvonne, Hirsch Daniela, Rotter Nicole
Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty Mannheim, University of Heidelberg, Germany.
Tissue Engineering and Biofabrication Laboratory, Institute for Biomechanics, ETH Zurich, Switzerland.
Adv Ther (Weinh). 2024 Mar 12;7(6). doi: 10.1002/adtp.202300441. eCollection 2024 Jun.
The gold standard of auricular reconstruction involves manual graft assembly from autologous costal cartilage. The intervention may require multiple surgical procedures and lead to donor-site morbidity, while the outcome is highly dependent on individual surgical skills. A tissue engineering approach provides the means to produce cartilage grafts of a defined shape from autologous chondrocytes. The use of autologous cells minimizes the risk of host immune response; however, factors such as biomaterial compatibility and in vitro maturation of the tissue-engineered (TE) cartilage may influence the engraftment and shape-stability of TE implants. Here, this work tests the biocompatibility of bioprinted autologous cartilage constructs in a rabbit model. The TE cartilage is produced by embedding autologous auricular chondrocytes into hyaluronan transglutaminase (HATG) based bioink, previously shown to support chondrogenesis in human auricular chondrocytes in vitro and in immunocompromised xenotransplantation models in vivo. A drastic softening and loss of cartilage markers, such as sulfated glycosaminoglycans (GAGs) and collagen type II are observed. Furthermore, fibrous encapsulation and partial degradation of the transplanted constructs are indicative of a strong host immune response to the autologous TE cartilage. The current study thus illustrates the crucial importance of immunocompetent autologous animal models for the evaluation of TE cartilage function and compatibility.
耳廓重建的金标准是使用自体肋软骨进行手工移植组装。该干预可能需要多次外科手术，并导致供体部位出现并发症，而其结果高度依赖于个体的手术技巧。组织工程方法提供了一种手段，可以从自体软骨细胞中制造出具有特定形状的软骨移植物。使用自体细胞可将宿主免疫反应的风险降至最低；然而，生物材料相容性和组织工程（TE）软骨的体外成熟等因素可能会影响TE植入物的植入和形状稳定性。在此，本研究在兔模型中测试了生物打印自体软骨构建体的生物相容性。TE软骨是通过将自体耳廓软骨细胞嵌入基于透明质酸转谷氨酰胺酶（HATG）的生物墨水中制成的，此前已证明该生物墨水在体外可支持人耳廓软骨细胞的软骨形成，并在体内免疫受损的异种移植模型中也有此作用。观察到软骨标记物如硫酸化糖胺聚糖（GAGs）和II型胶原出现明显软化和丢失。此外，移植构建体的纤维包裹和部分降解表明宿主对自体TE软骨有强烈的免疫反应。因此，本研究说明了具有免疫活性的自体动物模型在评估TE软骨功能和相容性方面的至关重要性。
