Successful periodontal repair and regeneration requires the coordinated responses from soft and hard tissues as well as the soft tissue–to–bone interfaces. Inspired by the hierarchical structure of native periodontal tissues, tissue engineering technology provides unique opportunities to coordinate multiple cell types into scaffolds that mimic the natural periodontal structure in vitro. In this study, we designed and fabricated highly ordered multicompartmental scaffolds by melt electrowriting, an advanced 3-dimensional (3D) printing technique. This strategy attempted to mimic the characteristic periodontal microenvironment through multicompartmental constructs comprising 3 tissue-specific regions: 1) a bone compartment with dense mesh structure, 2) a ligament compartment mimicking the highly aligned periodontal ligaments (PDLs), and 3) a transition region that bridges the bone and ligament, a critical feature that differentiates this system from mono- or bicompartmental alternatives. The multicompartmental constructs successfully achieved coordinated proliferation and differentiation of multiple cell types in vitro within short time, including both ligamentous- and bone-derived cells. Long-term 3D coculture of primary human osteoblasts and PDL fibroblasts led to a mineral gradient from calcified to uncalcified regions with PDL-like insertions within the transition region, an effect that is challenging to achieve with mono- or bicompartmental platforms. This process effectively recapitulates the key feature of interfacial tissues in periodontium. Collectively, this tissue-engineered approach offers a fundament for engineering periodontal tissue constructs with characteristic 3D microenvironments similar to native tissues. This multicompartmental 3D printing approach is also highly compatible with the design of next-generation scaffolds, with both highly adjustable compartmentalization properties and patient-specific shapes, for multitissue engineering in complex periodontal defects.

成功的牙周修复和再生需要软组织和硬组织以及软组织-骨界面的协调反应。受天然牙周组织分层结构的启发，组织工程技术提供了独特的机会，可以将多种细胞类型协调到体外模拟天然牙周结构的支架中。在这项研究中，我们通过熔融电写（一种先进的 3 维（3D）打印技术）设计并制造了高度有序的多室支架。该策略试图通过包含 3 个组织特异性区域的多隔室构建体来模拟特征性牙周微环境：1) 具有致密网状结构的骨隔室，2) 模拟高度排列的牙周韧带 (PDL) 的韧带隔室，3) 连接骨骼和韧带的过渡区域，这是将该系统与单室或双室替代系统区分开来的关键特征。多室构建体在短时间内成功地在体外实现了多种细胞类型的协同增殖和分化，包括韧带和骨源性细胞。原代人成骨细胞和 PDL 成纤维细胞的长期 3D 共培养导致了从钙化区域到未钙化区域的矿物质梯度，在过渡区域内插入了 PDL 样插入物，这种效果很难通过单室或双室平台实现。这个过程有效地概括了牙周组织界面组织的关键特征。集体，这种组织工程方法为工程牙周组织构建体提供了基础，该构建体具有类似于天然组织的特征 3D 微环境。这种多室 3D 打印方法也与下一代支架的设计高度兼容，具有高度可调节的分区特性和患者特定的形状，用于复杂牙周缺损的多组织工程。