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JOURNAL OF PERIODONTOLOGY · 2023 · IF 4.3

Stem-cell based soft tissue substitutes:engineering of cross-linked polylysine-hyaluronic acid microspheres ladened with gingival mesenchymal stem cells for collagen tissue regeneration and angiogenesis

Jing Ni,Mengdi Li,Chaolun Li,Zhe Zhong,Hongwei Xi,Yiqun Wu

Background : The aim of this study was to construct crosslinked polylysine-hyaluronic acid microspheres (pl-HAM) ladened with gingival mesenchymal stem cells (GMSCs) and explore its biologic behavior in soft tissue regeneration. Methods : The effects of the crosslinked pl-HAM on the biocompatibility and the recruitment of L-929 cells and GMSCs were detected in vitro. Moreover, the regeneration of subcutaneous collagen tissue, angiogenesis and the endogenous stem cells recruitment were investigated in vivo. We also detected the cell developing capability of pl-HAMs. Results : The crosslinked pl-HAMs appeared to be completely spherical-shaped particles and had good biocompatibility. L-929 cells and GMSCs grew around the pl-HAMs and increased gradually. Cell migration experiments showed that pl-HAMs combined with GMSCs could promote the migration of vascular endothelial cells significantly. Meanwhile, the GFP-GMSCs in the pl-HAM group still remain in the soft tissue regeneration area 2 weeks after surgery. The results of in vivo studies showed that denser collagen deposition and more angiogenesis-related indicator CD31 expression in the pl-HAMs+ GMSCs + GeL group compared to the pl-HAMs + GeL group. Immunofluorescence showed that CD44, CD90, CD73 co-staining positive cells surrounded the microspheres in both pl-HAMs + GeL group and pl-HAM + GMSCs + GeL group. Conclusions : The crosslinked pl-HAM ladened with GMSCs system could provide a suitable microenvironment for collagen tissue regeneration, angiogenesis and endogenous stem cells recruitment, which may be an alternative to autogenous soft tissue grafts for minimally invasive treatments for periodontal soft tissue defects in the future. This article is protected by copyright. All rights reserved

CAS / MDL: 3945-69-5 9004-61-9
研究领域: 组织工程 · 再生医学 · 牙科科学 · 生物材料
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Polyphenol-based coacervate droplets as building blocks for protocells and prototissues

Qi Xie,Wei Chen,Zijian Huang,Yuan Gao,Haoyu Zhang,Zhanhao Zhou,Samira Batur,Chuansheng Fu,Jiao Zhang,Conglian Yang,Junjun Liu,Li Kong,Zhiping Zhang

Despite the nascent stage of research into protocells and prototissues, their substantial potential has increasingly positioned them as a focal point in recent years. The bottom-up reconstruction of life systems is gradually garnering widespread attention. In this study, a type of protocells and corresponding prototissues based on polyphenol coacervate droplets were developed via hydrogen bond interactions. The droplets exhibited properties reminiscent of cytoplasm, enriching a wide range of substances. Upon further modification with lipid bilayers, the protocells not only achieved a structural resemblance to natural cells, but also effectively maintained the stability. Prototissues formed by the orderly aggregation of protocells can not only encapsulate living cells, but also maintain the structural integrity and function of both artificial and living cells. At the macroscopic level, the prototissues were injectable, customizable in shape, bioadhesive, and capable of long-term retention in vivo. Moreover, the prototissues showed no obvious inflammatory responses. Polyphenol-based protocells and tissues with unique characteristics may offer new insights for research and applications in organoids, transplantation, and medical devices.

研究领域: 合成生物学 · 生物物理学 · 材料科学 · 生物工程 · 细胞生物学 · 组织工程
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Nature Communications · 2022 ·Vol. 13 ·期 1 ·1-11 · IF 17.694

High-throughput production of functional prototissues capable of producing NO for vasodilation

Zhang Xiangxiang,Li Chao,Liu Fukai,Mu Wei,Ren Yongshuo,Yang Boyu,Han Xiaojun

Bottom-up synthesis of prototissues helps us to understand the internal cellular communications in the natural tissues and their functions, as well as to improve or repair the damaged tissues. The existed prototissues are rarely used to improve the function of living tissues. We demonstrate a methodology to produce spatially programmable prototissues based on the magneto-Archimedes effect in a high-throughput manner. More than 2000 prototissues are produced once within 2 h. Two-component and three-component spatial coded prototissues are fabricated by varying the addition giant unilamellar vesicles order/number, and the magnetic field distributions. Two-step and three-step signal communications in the prototissues are realized using cascade enzyme reactions. More importantly, the two-component prototissues capable of producing nitric oxide cause vasodilation of rat blood vessels in the presence of glucose and hydroxyurea. The tension force decreases 2.59 g, meanwhile the blood vessel relaxation is of 31.2%. Our works pave the path to fabricate complicated programmable prototissues, and hold great potential in the biomedical field.

研究领域: 生物医学工程 · 组织工程 · 分子生物学
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Acta Biomaterialia · 2023 · IF 9.7

Aligned lovastatin-loaded electrospun nanofibers regulate collagen organization and reduce scar formation

Zuhan Chen,Lingfei Xiao,Chaoyu Hu,Zixia Shen,Encheng Zhou,Shichen Zhang,Yanfeng Wang

Excessive scar formation caused by cutaneous injury leads to pruritus, pain, contracture, dyskinesia, and unpleasant appearance. Functional wound dressings are designed to accelerate wound healing and reduce scar formation. In this study, we fabricated aligned or random polycaprolactone/silk fibroin electrospun nanofiber membranes with or without lovastatin loading, and then evaluated their scar-inhibitory effects on wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity , and biocompatibility. Furthermore, nanofibers’ perpendicular placement to the tension direction of the wound most effectively reduced scar formation (the scar area decreased by 66.9%) and promoted skin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated collagen organization in the early stage of wound healing. Moreover, lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and lovastatin synergistically inhibited mechanical transduction and fibrosis progression, further reducing scar formation. In summary, our study may provide an effective scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients' wounds, and the addition of lovastatin can further inhibit scar formation. Statement of significance In vivo, cells and collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate scar formation. Electrospun nanofibers’ perpendicular placement to the tension direction of the wound most effectively reduces scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and lovastatin could inhibit mechanical transduction and fibrosis progression synergistically, further reducing scar formation. This study proves that combining topographical cues of wound dressing and drugs would be a promising therapy for clinical scar management.

CAS / MDL: 920-66-1
研究领域: 生物医学工程 · 伤口愈合 · 组织工程 · 药剂学
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