Construction of tissue-engineered bladders using an artificial acellular nanocomposite scaffold loaded with stromal vascular fraction secretome
Construction of tissue-engineered bladders using an artificial acellular nanocomposite scaffold loaded with stromal vascular fraction secretome
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DOI：
10.1016/j.actbio.2023.05.041
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发表时间：
2023-07-25
影响因子：
9.7
通讯作者：
Jia，Ruipeng
中科院分区：
文献类型：
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作者：
Zhao，Feng;Yang，Tianli;Jia，Ruipeng
组织工程方法为重建膀胱组织提供了有前景的替代策略；然而，移植细胞的保留率低和可能的排斥风险限制了它们的治疗效果。由于缺乏合适的支架材料来支持各种细胞类型的需求，临床适用性进一步受到限制。在本研究中，我们开发了一种人工纳米支架系统，该系统由加载到沸石咪唑框架-8（ZIF-8）纳米颗粒上的基质血管部分（SVF）分泌组（Sec）组成，然后将其掺入膀胱无细胞基质中。这种人工脱细胞纳米复合支架（ANS）可以实现梯度降解并缓慢释放SVF-Sec以促进组织再生。此外，即使经过长期冷冻保存，这种完全脱细胞的膀胱纳米支架材料仍然保持其功效。在大鼠膀胱置换模型中，ANS 移植表现出强大的促血管生成能力，并诱导 M2 巨噬细胞极化，以促进组织再生和恢复膀胱功能。我们的研究证明了ANS的安全性和有效性，它可以发挥类似干细胞的作用，同时避免细胞疗法的缺点。此外，ANS可以替代基于细胞结合支架材料的膀胱再生模型，具有临床应用的潜力。意义声明本研究旨在开发一种负载基质血管成分（SVF）分泌组的梯度可降解人工无细胞纳米复合支架（ANS）用于康复膀胱。使用各种体外方法以及基于大鼠和斑马鱼的体内模型，对开发的 ANS 的有效性和安全性进行了评估。结果表明，即使在长期冷冻保存后，ANS 仍能实现梯度降解并缓慢释放 SVF 分泌组以促进组织再生。此外，ANS 移植表现出强大的促血管生成能力，并诱导 M2 巨噬细胞极化，以促进膀胱替代模型中的组织再生和恢复膀胱功能。我们的研究表明ANS可能取代基于细胞结合支架材料的膀胱再生模型，并具有潜在的临床应用
Tissue engineering approaches offer promising alternative strategies for reconstructing bladder tissue; however, the low retention of transplanted cells and the possible risk of rejection limit their therapeutic efficacy. Clinical applicability is further limited by the lack of suitable scaffold materials to support the needs of various cell types. In the present study, we developed an artificial nanoscaffold system consisting of stromal vascular fraction (SVF) secretome (Sec) loaded onto zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, which were then incorporated into bladder acellular matrix. This artificial acellular nanocomposite scaffold (ANS) can achieve gradient degradation and slowly release SVF-Sec to promote tissue regeneration. Furthermore, even after long-term cryopreservation, this completely acellular bladder nanoscaffold material still maintains its efficacy. In a rat bladder replacement model, ANS transplantation demonstrated potent proangiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function. Our study demonstrates the safety and efficacy of the ANS, which can play a stem cell-like role while avoiding the disadvantages of cell therapy. Furthermore, the ANS can replace the bladder regeneration model based on cell-binding scaffold materials and has the potential for clinical application.Statement of significanceThis study aimed to develop a gradient-degradable artificial acellular nanocomposite scaffold (ANS) loaded with stromal vascular fraction (SVF) secretome for rehabilitating bladders. Using various in vitro methods as well as rat- and zebrafish-based in vivo models, the developed ANS was assessed for efficacy and safety. Results indicated that the ANS achieved gradient degradation and slowly released the SVF secretome to promote tissue regeneration, even after long-term cryopreservation. Furthermore, ANS transplantation demonstrated a potent pro-angiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function in a bladder replacement model. Our study demonstrates that ANS may replace bladder regeneration models based on cell-binding scaffold materials and have potential clinical application