Incorporation of intact elastin scaffolds in tissue-engineered collagen-based vascular grafts
Incorporation of intact elastin scaffolds in tissue-engineered collagen-based vascular grafts
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DOI：
10.1089/ten.2004.10.1526
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发表时间：
2004-09-01
影响因子：
--
通讯作者：
Sambanis, A
中科院分区：
文献类型：
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作者：
Berglund, JD;Nerem, RM;Sambanis, A
尽管基于胶原蛋白的组织工程血管（TEBV）具有许多有趣的特性，并已被用于研究血管生物学的各个方面，但这些构建物太弱而不能作为旁路移植物植入体内研究。这项研究提出了一种方法，将有组织的，完整的弹性蛋白纳入胶原蛋白为基础的TEBV，以形成混合结构，更好地模拟动脉生理学和表现出改善的机械性能。用一系列高压灭菌和化学处理消化猪颈动脉以获得分离的弹性蛋白支架。通过免疫组织化学和氨基酸分析验证弹性蛋白纯度。将分离的支架与I型胶原和人真皮成纤维细胞（HDF）或大鼠平滑肌细胞（RASM）组合以形成弹性蛋白杂合TEBV。与不含外源性弹性蛋白支架的胶原对照构建体相比，杂交构建体表现出增加的拉伸强度（HDF中为11倍; RASM中为7.5倍）和线性刚度模量（HDF中为4倍; RASM中为1.8倍）。通过逐步应力松弛分析确定，TEBV的粘弹性也随着辅助弹性蛋白支架的添加而改善。胶原对照结构中的大部分变形阻力源于粘性流体样效应，而弹性蛋白混合结构表现出更理想的弹性固体机械行为。因此，弹性蛋白支架可以帮助重建天然动脉的弹性特性。未来的挑战包括刺激胶原蛋白基质的适当重组或合成，以提供植入所需的强度和粘弹特性。
Although collagen-based tissue-engineered blood vessels (TEBVs) have many interesting properties and have been utilized to study aspects of vascular biology, these constructs are too weak to be implanted as bypass grafts for in vivo investigations. This study presents a method to incorporate organized, intact elastin into collagen-based TEBVs to form hybrid constructs that better mimic arterial physiology and exhibit improved mechanical properties. Porcine carotids were digested with a series of autoclave and chemical treatments to elicit isolated elastin scaffolds. Elastin purity was verified via immunohistochemistry and amino acid analysis. Isolated scaffolds were combined with type I collagen and either human dermal fibroblasts (HDFs) or rat smooth muscle cells (RASMs) to form an elastin hybrid TEBV. Hybrid constructs exhibited increased tensile strengths (11-fold in HDFs; 7.5-fold in RASMs) and linear stiffness moduli (4-fold in HDFs; 1.8-fold in RASMs) compared with collagen control constructs with no exogenous elastin scaffold. Viscoelastic properties of the TEBVs also improved with the addition of an ancillary elastin scaffold as determined through stepwise stress relaxation analysis. Whereas the majority of resistance to deformation in collagen control constructs stemmed from viscous fluidlike effects, elastin hybrid constructs exhibited more ideal elastic solid mechanical behavior. Thus, elastin scaffolds can help recreate the elastic properties of native arteries. Future challenges include stimulating appropriate reorganization or synthesis of the collagen matrix to provide the necessary strength and viscoelastic properties for implantation.