School of Biomedical Convergence Engineering, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan, Kyungbuk, 50612, Republic of Korea; Future IT Innovation Laboratory, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea; POSTECH-Catholic Biomedical Engineering Institute, POSTECH, Pohang, Kyungbuk, 37673, Republic of Korea.
POSTECH-Catholic Biomedical Engineering Institute, POSTECH, Pohang, Kyungbuk, 37673, Republic of Korea; Department of Mechanical Engineering, POSTECH, 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea.
Biomaterials. 2021 May;272:120776. doi: 10.1016/j.biomaterials.2021.120776. Epub 2021 Mar 24.
Despite many significant advances in 3D cell printing for skin, a disease model displaying the pathological processes present in the native skin has not been reported yet. Therefore, we were motivated for modeling a 3D diseased skin tissue with pathophysiological hallmarks of type 2 diabetes in vitro based on 3D cell printing technique. By stimulating epidermal-dermal intercellular crosstalk found in the native skin, it was hypothesized that normal keratinocytes would be differentiated as diabetic epidermis when interacting with the diabetic dermal compartment. To prove this, a novel wounded skin model was successfully devised during tissue maturation in vitro. Interestingly, the slow re-epithelization was observed in our diabetic model, which is a representative hallmark of diabetic skin. Using the versatility of 3D cell printing, the structural similarities and diabetic properties of the model were further augmented by addition of perfusable vascularized diabetic hypodermis. Insulin resistance, adipocyte hypertrophy, inflammatory reactions, and vascular dysfunction, as the typical hallmarks in diabetes, were found under hyperglycemia. Finally, the feasibility of this new disease model for drug development was successfully demonstrated through application of test drugs. We trust that this study provides a pioneering step towards 3D cell printing-based in vitro skin disease modeling.
尽管 3D 细胞打印在皮肤方面取得了许多重大进展，但尚未报道能够显示天然皮肤中存在的病理过程的疾病模型。因此，我们的动机是基于 3D 细胞打印技术，体外模拟具有 2 型糖尿病病理生理特征的 3D 病变皮肤组织。通过刺激天然皮肤中存在的表皮-真皮细胞间相互作用，假设正常角质形成细胞在与糖尿病真皮隔室相互作用时会分化为糖尿病表皮。为了证明这一点，我们在体外组织成熟过程中成功设计了一种新的创伤皮肤模型。有趣的是，我们的糖尿病模型中观察到缓慢的再上皮化，这是糖尿病皮肤的代表性特征之一。利用 3D 细胞打印的多功能性，通过添加可灌注的血管化糖尿病皮下组织进一步增强了模型的结构相似性和糖尿病特性。在高血糖条件下，发现了胰岛素抵抗、脂肪细胞肥大、炎症反应和血管功能障碍等糖尿病的典型特征。最后，通过应用测试药物成功证明了这种新疾病模型在药物开发中的可行性。我们相信，这项研究为基于 3D 细胞打印的体外皮肤疾病建模提供了一个开创性的步骤。
