International Journal of Nanomedicine
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2022
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IF 7.033
Chentao Shen,Jian Liu,Qiyi Lu,Guihua Wang,Zhenxing Wang,Lu Liu
Purpose Successful intestinal tissue engineering requires specialized biocompatible scaffolds and a vibrant vascularization microenvironment. A pre-vascularized chamber can provide both in vivo, but there is little report on using it to improve intestinal regeneration. Besides, researchers have found that gelatin is highly biocompatible and graphene oxide (GO) can be used to improve mechanical properties. Thus, applying a pre-vascularized chamber fabricated gelatin and GO into intestinal tissue engineering is worth a try.Materials and Methods In this study, an investigation into the physicochemical and mechanical properties as well as biocompatibility of the electrospun graphene oxide-gelatin (GO-Gel) scaffolds were conducted in vitro. Meanwhile, a pre-vascularized GO-Gel (V-GO-Gel) chamber model was built by implanting the scaffold around the mesenteric vessels in rat. After vascularization process, the chamber was used to repair the perforation and then assessed by histology and immunofluorescence analyses.Results These porous scaffolds were mechanical improved with GO incorporated into gelatin. Further, the cell adherence, viability and morphology on the scaffolds were maintained. The V-GO-Gel chamber model was successfully built and effective enhanced the repair of the intestinal wall than the other group without recurrence or complications.Conclusion The V-GO-Gel chamber shows promising therapeutic potential in the repair of intestinal wall defects.
研究领域:
组织工程
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生物医学工程
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材料科学
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外科研究
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2021
·Vol. 12
·期 1
·1-16
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IF 6.832
Zhang Xinxin,Jiang Xiaorui,Jiang Shan,Cai Xiyu,Yu Shengji,Pei Guoxian
Background Tissue-engineered bone grafts (TEBGs) that undergo vascularization and neurotization evolve into functioning bone tissue. Previously, we verified that implanting sensory nerve tracts into TEBGs promoted osteogenesis. However, the precise mechanisms and interaction between seed cells were not explored. In this study, we hypothesized that neurotization may influence the osteogenesis of TEBGs through vascularization. Methods We cultured rat Schwann cells (SCs), aortic endothelial cells (AECs), and bone marrow-derived mesenchymal stem cells (BM-MSCs) and then obtained BM-MSC-derived induced endothelial cells (IECs) and induced osteoblasts (IOBs). IECs and AECs were cultured in an SC-conditioned medium (SC-CM) to assess proliferation, migration, capillary-like tube formation, and angiogenesis, and the vascular endothelial growth factor (VEGF) levels in the supernatants were detected. We established an indirect coculture model to detect the expression of nestin and VEGF receptors in IECs and tissue inhibitor of metalloproteinase (TIMP)-2 in SCs. Then, SCs, IECs, and IOBs were labeled and loaded into a β-tricalcium phosphate scaffold to induce prevascularization, and the scaffold was implanted into a 6-mm-long defect of rat femurs. Three groups were set up according to the loaded cells: I, SCs, and IECs (coculture for 3 days) plus IOBs; II, IECs (culture for 3 days) plus IOBs; III, IOBs. Nestin and TIMP-2 expression and osteogenesis of TEBGs were evaluated at 12 weeks post-implantation through histological and radiological assessments. Results We found that SC-CM promoted IEC proliferation, migration, capillary-like tube formation, and angiogenesis, but no similar effects were observed for AECs. IECs expressed nestin extensively, while AECs barely expressed nestin, and SC-CM promoted the VEGF secretion of IECs. In the coculture model, SCs promoted nestin and VEGF receptor expression in IECs, and IECs inhibited TIMP-2 expression in SCs. The promotion of prevascularized TEBGs by SCs and IECs in group I augmented new bone formation at 6 and 12 weeks. Nestin expression was higher in group I than in the other groups, while TIMP-2 expression was lower at 12 weeks. Conclusions This study demonstrated that SCs can promote TEBG osteogenesis via IECs and further revealed the related specific characteristics of IECs, providing preliminary cytological evidence for neurotization of TEBGs.
研究领域:
组织工程
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再生医学
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细胞生物学
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骨再生
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血管化
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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
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组织工程
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再生医学
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牙科科学
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细胞生物学
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DOI
PubMed
高影响因子
Bioactive Materials
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2023
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IF 18.9
Haofei Li,Yulian Shang,Qi Feng,Yang Liu,Junlin Chen,Hua Dong
Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.
研究领域:
生物医学工程
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组织工程
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糖尿病研究
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细胞治疗
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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）