Kuang Rong, Zhang Zhanpeng, Jin Xiaobing, Hu Jiang, Shi Songtao, Ni Longxing, Ma Peter X
Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA; State Key Laboratory of Military Stomatology, Department of Operative Dentistry and Endodontics, School of Stomatology, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Acta Biomater. 2016 Mar;33:225-34. doi: 10.1016/j.actbio.2016.01.032. Epub 2016 Jan 27.
Dental pulp infection and necrosis are widespread diseases. Conventional endodontic treatments result in a devitalized and weakened tooth. In this work, we synthesized novel star-shaped polymer to self-assemble into unique nanofibrous spongy microspheres (NF-SMS), which were used to carry human dental pulp stem cells (hDPSCs) into the pulp cavity to regenerate living dental pulp tissues. It was found that NF-SMS significantly enhanced hDPSCs attachment, proliferation, odontogenic differentiation and angiogenesis, as compared to control cell carriers. Additionally, NF-SMS promoted vascular endothelial growth factor (VEGF) expression of hDPSCs in a 3D hypoxic culture. Hypoxia-primed hDPSCs/NF-SMS complexes were injected into the cleaned pulp cavities of rabbit molars for subcutaneous implantation in mice. After 4 weeks, the hypoxia group significantly enhanced angiogenesis inside the pulp chamber and promoted the formation of ondontoblast-like cells lining along the dentin-pulp interface, as compared to the control groups (hDPSCs alone group, NF-SMS alone group, and hDPSCs/NF-SMS group pre-cultured under normoxic conditions). Furthermore, in an in situ dental pulp repair model in rats, hypoxia-primed hDPSCs/NF-SMS were injected to fully fill the pulp cavity and regenerate pulp-like tissues with a rich vasculature and a histological structure similar to the native pulp.
Vascularization is key to the regeneration of many vital tissues. However, it is challenging to create a suitable microenvironment for stem cells to regenerate vascularized tissue structure. This manuscript reports a novel star-shaped block copolymer that self-assembles into unique nanofibrous spongy microspheres, which as an injectable scaffold recapitulate the cell-cell and cell-matrix interactions in development. Using a clinically-relevant surgical procedure and a hypoxic treatment, the nanofibrous spongy microspheres were used to deliver stem cells and successfully regenerate dental pulp with a rich vasculature and a complex histologic structure similar to that of the native dental pulp. The novel microspheres can likely be used to regenerate many other vascularized tissues.
牙髓感染和坏死是常见疾病。传统的牙髓治疗会导致牙齿失去活力并变脆弱。在本研究中，我们合成了新型星形聚合物，使其自组装成独特的纳米纤维海绵微球（NF-SMS），用于将人牙髓干细胞（hDPSCs）输送到牙髓腔以再生有活力的牙髓组织。结果发现，与对照细胞载体相比，NF-SMS显著增强了hDPSCs的附着、增殖、成牙本质分化和血管生成。此外，NF-SMS在三维缺氧培养中促进了hDPSCs的血管内皮生长因子（VEGF）表达。将缺氧预处理的hDPSCs/NF-SMS复合物注入兔磨牙清洁后的牙髓腔，然后在小鼠皮下植入。4周后，与对照组（单独的hDPSCs组、单独的NF-SMS组以及在常氧条件下预培养的hDPSCs/NF-SMS组）相比，缺氧组显著增强了牙髓腔内的血管生成，并促进了沿牙本质-牙髓界面排列的成牙本质样细胞的形成。此外，在大鼠原位牙髓修复模型中，注入缺氧预处理的hDPSCs/NF-SMS可完全填充牙髓腔，并再生出具有丰富血管和与天然牙髓相似组织结构的牙髓样组织。
血管化是许多重要组织再生的关键。然而，为干细胞创造合适的微环境以再生血管化组织结构具有挑战性。本手稿报道了一种新型星形嵌段共聚物，它自组装成独特的纳米纤维海绵微球，作为可注射支架可重现发育过程中的细胞-细胞和细胞-基质相互作用。通过临床相关的手术操作和缺氧处理，纳米纤维海绵微球用于输送干细胞，并成功再生出具有丰富血管和与天然牙髓相似复杂组织结构的牙髓。这种新型微球可能可用于再生许多其他血管化组织。
