Ma Yufei, Ji Yuan, Zhong Tianyu, Wan Wanting, Yang Qingzhen, Li Ang, Zhang Xiaohui, Lin Min
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, No. 98 Xiwu Road, Xi'an 710004, P.R. China.
ACS Biomater Sci Eng. 2017 Dec 11;3(12):3534-3545. doi: 10.1021/acsbiomaterials.7b00601. Epub 2017 Oct 26.
Periodontitis is an inflammatory disease worldwide that may result in periodontal defect (especially alveolar bone defect) and even tooth loss. Stem-cell-based approach combined with injectable hydrogels has been proposed as a promising strategy in periodontal treatments. Stem cells fate closely depends on their extracellular matrix (ECM) characteristics. Hence, it is necessary to engineer an appropriate injectable hydrogel to deliver stem cells into the defect while serving as the ECM during healing. Therefore, stem cell-ECM interaction should be studied for better stem cell transplantation. In this study, we developed a bioprinting-based strategy to study stem cell-ECM interaction and thus screen an appropriate ECM for in vivo repair of alveolar bone defect. Periodontal ligament stem cells (PDLSCs) were encapsulated in injectable, photocrosslinkable composite hydrogels composed of gelatin methacrylate (GelMA) and poly(ethylene glycol) dimethacrylate (PEGDA). PDLSC-laden GelMA/PEGDA hydrogels with varying composition were efficiently fabricated via a 3D bioprinting platform by controlling the volume ratio of GelMA-to-PEGDA. PDLSC behavior and fate were found to be closely related to the engineered ECM composition. The 4/1 GelMA/PEGDA composite hydrogel was selected since the best performance in osteogenic differentiation in vitro. Finally, in vivo study indicated a maximal and robust new bone formation in the defects treated with the PDLSC-laden hydrogel with optimized composition as compared to the hydrogel alone and the saline ones. The developed approach would be useful for studying cell-ECM interaction in 3D and paving the way for regeneration of functional tissue.
牙周炎是一种全球性的炎症性疾病，可能导致牙周缺损（尤其是牙槽骨缺损）甚至牙齿脱落。基于干细胞的方法与可注射水凝胶相结合，已被提议作为牙周治疗的一种有前景的策略。干细胞的命运密切依赖于其细胞外基质（ECM）特征。因此，有必要设计一种合适的可注射水凝胶，将干细胞输送到缺损部位，同时在愈合过程中充当细胞外基质。因此，为了更好地进行干细胞移植，应该研究干细胞与细胞外基质的相互作用。在本研究中，我们开发了一种基于生物打印的策略来研究干细胞与细胞外基质的相互作用，从而筛选出一种合适的细胞外基质用于牙槽骨缺损的体内修复。牙周膜干细胞（PDLSCs）被封装在由甲基丙烯酸明胶（GelMA）和聚（乙二醇）二甲基丙烯酸酯（PEGDA）组成的可注射、光交联复合水凝胶中。通过3D生物打印平台，通过控制GelMA与PEGDA的体积比，高效制备了不同组成的载有PDLSC的GelMA/PEGDA水凝胶。发现PDLSC的行为和命运与工程化的细胞外基质组成密切相关。选择4/1的GelMA/PEGDA复合水凝胶，因为它在体外成骨分化方面表现最佳。最后，体内研究表明，与单独的水凝胶和生理盐水组相比，用优化组成的载有PDLSC的水凝胶治疗的缺损部位有最大且强劲的新骨形成。所开发的方法将有助于在三维空间中研究细胞与细胞外基质的相互作用，并为功能性组织的再生铺平道路。
