Dai Yichen, Wang Peter, Mishra Apurva, You Kui, Zong Yuheng, Lu Wen Feng, Chow Edward Kai-Hua, Preshaw Philip M, Huang Dejian, Chew Jacob Ren Jie, Ho Dean, Sriram Gopu
Faculty of Dentistry, National University of Singapore, Singapore, 119085, Singapore.
Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, 117583, Singapore.
Adv Healthc Mater. 2025 May;14(13):e2402727. doi: 10.1002/adhm.202402727. Epub 2024 Dec 17.
Regeneration of oral soft tissue defects, including mucogingival defects associated with the recession or loss of gingival and/or mucosal tissues around teeth and implants, is crucial for restoring oral tissue form, function, and health. This study presents a novel approach using three-dimensional (3D) bioprinting to fabricate individualized grafts with precise size, shape, and layer-by-layer cellular organization. A multicomponent polysaccharide/fibrinogen-based bioink is developed, and bioprinting parameters are optimized to create shape-controlled oral soft tissue (gingival) constructs. Rheological, printability, and shape-fidelity assays, demonstrated the influence of thickener concentration and print parameters on print resolution and shape fidelity. Artificial intelligence (AI)-derived tool enabled streamline the iterative bioprinting parameter optimization and analysis of the interaction between the bioprinting parameters. The cell-laden polysaccharide/fibrinogen-based bioinks exhibited excellent cellular viability and shape fidelity of shape-controlled, full-thickness gingival tissue constructs over the 18-day culture period. While variations in thickener concentrations within the bioink minimally impact the cellular organization and morphogenesis (gingival epithelial, connective tissue, and basement membrane markers), they influence the shape fidelity of the bioprinted constructs. This study represents a significant step toward the biofabrication of personalized soft tissue grafts, offering potential applications in the repair and regeneration of mucogingival defects associated with periodontal disease and dental implants.
口腔软组织缺损的再生，包括与牙齿和种植体周围牙龈和/或粘膜组织退缩或丧失相关的粘膜牙龈缺损，对于恢复口腔组织的形态、功能和健康至关重要。本研究提出了一种使用三维（3D）生物打印来制造具有精确尺寸、形状和逐层细胞组织的个性化移植物的新方法。开发了一种基于多糖/纤维蛋白原的多组分生物墨水，并优化了生物打印参数以创建形状可控的口腔软组织（牙龈）构建体。流变学、可打印性和形状保真度分析证明了增稠剂浓度和打印参数对打印分辨率和形状保真度的影响。人工智能（AI）衍生工具能够简化迭代生物打印参数优化以及生物打印参数之间相互作用的分析。在18天的培养期内，基于多糖/纤维蛋白原的载细胞生物墨水在形状可控的全层牙龈组织构建体中表现出优异的细胞活力和形状保真度。虽然生物墨水中增稠剂浓度的变化对细胞组织和形态发生（牙龈上皮、结缔组织和基底膜标志物）的影响最小，但它们会影响生物打印构建体的形状保真度。这项研究代表了个性化软组织移植物生物制造的重要一步，为与牙周病和牙种植体相关的粘膜牙龈缺损的修复和再生提供了潜在应用。
