Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou 510182, China.
School and Hospital of Stomatology, Guangzhou Medical University, Guangzhou 510182, China.
Biomolecules. 2023 Jun 30;13(7):1062. doi: 10.3390/biom13071062.
Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.
水凝胶由于其类似细胞外基质的特性、对活细胞的包封能力以及可根据缺陷形状进行可定制的形状设计，已被广泛应用于通过三维（3D）生物打印来制造组织工程支架。然而，目前的水凝胶支架显示出有限的再生活性，特别是在牙周组织再生的应用中。在本研究中，我们试图开发一种新型的多组分水凝胶，该水凝胶具有良好的生物活性，能够包裹活细胞进行 3D 生物打印，并能够再生牙周软硬组织。该多组分水凝胶由明胶甲基丙烯酰（GelMA）、海藻酸钠（SA）和生物活性玻璃微球（BGM）组成，首先通过无细胞 3D 打印将其加工成水凝胶支架，以评估其可打印性和体外生物性能。无细胞 3D 打印的支架具有均匀的多孔结构和良好的溶胀能力。负载 BGM 的支架表现出良好的生物相容性、增强的成骨分化、形成磷灰石的能力和所需的机械强度。复合水凝胶进一步用作生物墨水，负载小鼠骨髓间充质干细胞（mBMSCs）和生长因子（BMP2 和 PDGF），用于制造牙周组织再生支架。水凝胶包裹的细胞在 3D 生物打印后仍保持良好的细胞活力，并在负载 BMP2 和 PDGF 的支架中表现出增强的成骨分化和软组织修复能力。值得注意的是，在 Beagle 犬牙周缺损中移植负载细胞和生长因子的支架后，观察到牙龈组织、牙周韧带和牙槽骨的显著再生。重要的是，在移植含有细胞和生长因子的支架 8 周后，治疗组中建立了重建的牙周结构。总之，我们开发了一种用于制造支架的生物活性复合生物墨水，适用于牙周组织缺损的重建和再生。
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