CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Wenjing Jin,Haiyan Wu,Jue Shi,Zihe Hu,Yanyan Zhou,Zhuo Chen,Changyu Shao,Ruikang Tang,Zhijian Xie
Dentin regeneration is a huge challenge because of its complicated structure and the shortage of odontoblasts. Unlike in vitro remineralization of dentin through supersaturation of calcium phosphate, the materials of mineralized collagen scaffolds could recruit the human dental pulp stem cells (hDPSCs) and induce their differentiation in vivo and achieve dentin repair. Inspired by the biomineralization of dentin, herein, mineralized collagen fibrils with various mineralization degrees and mechanical properties were prepared through biomolecule hyaluronic acid (HA) modification, and first time find the mechanical properties have a positive correlation with mineralization degree. When 1.2 mg/mL HA was used to modification, the mineralized HA-modified collagen scaffolds (HA-MCS) with similar modulus and stiffness to that of natural dentin could be obtained. Furthermore, testing ALP activity and alizarin red S staining experiments confirmed the HA-MCS with a biomimetic mechanical microenvironment could enhance the proliferation and differentiation of hDPSCs. Additionally, in vivo experiments performed on the beagle model further proved this point that HA-MCS with a biomimetic mechanical microenvironment could promote dentin regeneration. These results not only elucidate that the modulation of mechanical properties of biomaterials could enhance the proliferation and differentiation of stem cells, but also provide a strategy for hard tissue regeneration.
研究领域:
生物材料
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组织工程
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干细胞生物学
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牙科材料
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再生医学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2024
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IF 8.7
Zhuo Xie,Peimeng Zhan,Xinfang Zhang,Shuheng Huang,Xuetao Shi,Zhengmei Lin,Xianling Gao
Regenerative endodontic therapy is a promising approach to restore the vitality of necrotic teeth, however, pulp regeneration in mature permanent teeth remains a substantial challenge due to insufficient developmental signals. The dentin is embryologically and histologically similar to the pulp, which contains a cocktail of pulp-specific structural proteins and growth factors, thus we proposed an optimizing strategy to obtain dentin matrix extracted proteins (DMEP) and engineered a DMEP functionalized double network hydrogel, whose physicochemical property was tunable by adjusting polymer concentrations to synchronize with regenerated tissues. In vitro models showed that the biomimetic hydrogel with sustained release of DMEP provided a beneficial microenvironment for the encapsulation, propagation and migration of human dental pulp stem cells (hDPSCs). The odontogenic and angiogenic differentiation of hDPSCs were enhanced as well. To elicit the mechanism hidden in the microenvironment to guide cell fate, RNA sequencing was performed and 109 differential expression of genes were identified, the majority of which enriched in cell metabolism, cell differentiation and intercellular communications. The involvement of ERK, p38 and JNK MAPK signaling pathways in the process was confirmed. Of note, in vivo models showed that the injectable and in situ photo-crosslinkable hydrogel was user-friendly for root canal systems and was capable of inducing the regeneration of highly organized and vascularized pulp-like tissues in root segments that subcutaneously implanted into nude mice. Taken together, this study reported a facile and efficient way to fabricate a cell delivery hydrogel with pulp-specific developmental cues, which exhibited promising application and translation potential in future regenerative endodontic fields.
研究领域:
再生医学
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生物材料
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干细胞生物学
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组织工程
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牙科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2022
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IF 10.633
Xi Liang,Li Xie,Qingyuan Zhang,Ge Wang,Siyuan Zhang,Mingyan Jiang,Ruitao Zhang,Ting Yang,Xingyu Hu,Ziyang Yang,Weidong Tian
Combined injectable cell-laden microspheres and angiogenesis approaches are promising for functional vascularized endodontic regeneration. However, advanced microsphere designs and production techniques that benefit practical applications are rarely developed. Herein, gelatin methacryloyl (GelMA)-alginate core-shell microcapsules were fabricated to co-encapsulate human dental pulp stem cells (hDPSCs) and human umbilical vein endothelial cells (HUVECs) based on a coaxial electrostatic microdroplet technique. This technique enables high-throughput production, convenient collection, and minimal material waste. The average diameter of core-shell microcapsules was ∼359 µm, and that of GelMA cores was ∼278 µm. There were higher proliferation rates for hDPSCs and HUVECs co-encapsulated in the GelMA cores than for hDPSCs or HUVECs monoculture group. HUVECs assembled to form 3D capillary-like networks in co-culture microcapsules. Moreover, HUVECs promoted the osteo/odontogenic differentiation of hDPSCs in microcapsules. After 14 days of cultivation, prevascularized microtissues formed in microcapsules that contained abundant deposited extracellular matrix (ECM); no microcapsule aggregation occurred. In vivo studies confirmed that better microvessel formation and pulp-like tissue regeneration occurred in the co-culture group than in hDPSCs group. Thus, an effective platform for prevascularization microtissue preparation was proposed and showed great promise in endodontic regeneration and tissue engineering applications. Statement of significance Cell-laden microspheres combined with the proangiogenesis approach are promising in endodontic regeneration. We proposed GelMA-alginate core-shell microcapsules generated via the coaxial electrostatic microdroplet (CEM) method, which utilizes a double-lumen needle to allow for core-shell structures to form. The microcapsules were used for co-culturing hDPSCs and HUVECs to harvest large amounts of prevascularized microtissues, which further showed improved vascularization and pulp-like tissue regeneration in vivo . This CEM method and the microcapsule system have advantages of high-throughput generation, convenient collection, and avoid aggregation during long-term culturing. We proposed a high-effective platform for mass production of prevascularized microtissues, which exhibit great promise in the clinical transformation of endodontic regeneration and other applications in regenerative medicine.
研究领域:
生物材料
·
组织工程
·
再生医学
·
牙科科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）