The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury.

The use of bi-layer silk fibroin scaffolds and small intestinal submucosa matrices to support bladder tissue regeneration in a rat model of spinal cord injury.
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DOI:
10.1016/j.biomaterials.2014.05.044
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发表时间:
2014-08
期刊:
影响因子:
14
通讯作者:
Mauney, Joshua R.
Mauney, Joshua R.
中科院分区:
工程技术1区
文献类型:
--
作者:
Chung, Yeun Goo;Algarrahi, Khalid;Franck, Debra;Tu, Duong D.;Adam, Rosalyn M.;Kaplan, David L.;Estrada, Carlos R., Jr.;Mauney, Joshua R.

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神经源性膀胱重建肠膀胱成形术的不良副作用已经催生了替代移植物替代品的发展需求。研究双层丝素蛋白(SF)支架和小肠粘膜下层(SIS)基质在大鼠脊髓损伤(SCI)模型中支持膀胱组织再生和功能的能力。在SCI动物中用每种支架配置进行膀胱扩张,植入10周,并与非扩张对照组(正常和单独SCI)进行比较。在整个研究期间,仅接受SCI的动物显示出72%的存活率(13/18),而接受SIS和双层SF支架的SCI大鼠分别显示出83%(10/12)和75%(9/12)的存活率。组织学(Masson三色分析)和免疫组织化学(IHC)评价表明,两个植入物组均支持具有收缩蛋白表达[α-平滑肌肌动蛋白(α-SMA)和SM 22 α]的平滑肌层的从头形成以及表达细胞角蛋白(CK)和尿斑蛋白3A蛋白的多层尿路上皮的成熟。组织形态计量学分析显示,双层SF和SIS支架分别重建了单独SCI对照中存在的α-SMA+平滑肌束水平的64%和56%,而在所有实验组中检测到相似程度的CK+尿路刺激。平行评价显示,与SCI单独对照相比,所有再生组织中的血管面积和突触素+终扣程度相似。此外,还观察到植入两种基质配置后SCI动物中某些尿动力学参数的改善,例如峰值膀胱内压降低。本研究中提供的数据详细说明了脱细胞SIS和双层SF支架在神经原性膀胱模型中支持神经支配的血管化平滑肌和尿路上皮组织形成的能力。
Adverse side-effects associated with enterocystoplasty for neurogenic bladder reconstruction have spawned the need for the development of alternative graft substitutes. Bi-layer silk fibroin (SF) scaffolds and small intestinal submucosa (SIS) matrices were investigated for their ability to support bladder tissue regeneration and function in a rat model of spinal cord injury (SCI). Bladder augmentation was performed with each scaffold configuration in SCI animals for 10 wk of implantation and compared to non-augmented control groups (normal and SCI alone). Animals subjected to SCI alone exhibited a 72% survival rate (13/18) while SCI rats receiving SIS and bi-layer SF scaffolds displayed respective survival rates of 83% (10/12) and 75% (9/12) over the course of the study period. Histological (Masson’s trichrome analysis) and immunohistochemical (IHC) evaluations demonstrated both implant groups supported de novo formation of smooth muscle layers with contractile protein expression [α-smooth muscle actin (α-SMA) and SM22α] as well as maturation of multi-layer urothelia expressing cytokeratin (CK) and uroplakin 3A proteins. Histomorphometric analysis revealed bi-layer SF and SIS scaffolds respectively reconstituted 64% and 56% of the level of α-SMA+ smooth muscle bundles present in SCI-alone controls, while similar degrees of CK+ urothelium across all experimental groups were detected. Parallel evaluations showed similar degrees of vascular area and synaptophysin+ boutons in all regenerated tissues compared to SCI-alone controls. In addition, improvements in certain urodynamic parameters in SCI animals, such as decreased peak intravesical pressure, following implantation with both matrix configurations were also observed. The data presented in this study detail the ability of acellular SIS and bi-layer SF scaffolds to support formation of innervated, vascularized smooth muscle and urothelial tissues in a neurogenic bladder model.
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