Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, China.
Department of Stomatology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Sci Rep. 2017 Sep 5;7(1):10519. doi: 10.1038/s41598-017-11155-7.
Biomimetic intrafibrillarly-mineralized collagen (IMC) is a promising scaffold for bone regeneration because of its structural and functional similarity to natural bone. The objective of this study was to evaluate the bone regeneration potential of IMC loaded with autologous periodontal ligament stem cells (PDLSCs) in large bone defects in minipigs. A macroporous IMC with a bone-like subfibrillar nanostructure was fabricated using a biomimetic bottom-up approach. Non-healing full thickness defects were established on the cranial bone in minipigs, and IMC and hydroxyapatite (HA) scaffolds seeded with autologous PDLSCs were implanted into these defects. Computed tomographic imaging, histology staining, and atomic force microscopy were applied to evaluate to the quantity, micro/nano structures, and mechanical performance of the neo-bone after 12 weeks of implantation. Compared with HA, IMC showed superior regeneration properties characterized by the profuse deposition of new bony structures with a normal architecture and vascularization. Immunohistochemistry showed that the runt-related transcription factor 2 and transcription factor Osterix were highly expressed in the neo-bone formed by IMC. Furthermore, the nanostructure and nanomechanics of the neo-bone formed by IMC were similar to that of natural bone. This study provides strong evidence for the future clinical applications of the IMC-based bone grafts.
仿生纤维内矿化胶原（IMC）因其结构和功能与天然骨相似，是一种很有前途的骨再生支架。本研究旨在评估负载自体牙周膜干细胞（PDLSCs）的 IMC 在小型猪大骨缺损中的骨再生潜力。采用仿生自下而上的方法制备具有类骨亚纤维纳米结构的大孔 IMC。在小型猪颅骨上建立全层非愈合性缺损，将负载自体 PDLSCs 的 IMC 和羟基磷灰石（HA）支架植入这些缺损中。通过计算机断层扫描成像、组织学染色和原子力显微镜评估植入 12 周后新骨的数量、微/纳米结构和力学性能。与 HA 相比，IMC 表现出优越的再生特性，表现为大量具有正常结构和血管化的新骨结构的沉积。免疫组织化学显示，在 IMC 形成的新骨中， runt 相关转录因子 2 和转录因子 Osterix 高度表达。此外，IMC 形成的新骨的纳米结构和纳米力学与天然骨相似。这项研究为基于 IMC 的骨移植物的未来临床应用提供了有力证据。
