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Vascular Guidance: Microstructural Scaffold Patterning for Inductive Neovascularization

机译:血管指导:诱导新血管形成的微结构支架图案。

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Current tissue engineering techniques are limited by inadequate vascularisation and perfusion of cell-scaffold constructs. Microstructural patterning through biomimetic vascular channels within a polymer scaffold might induce neovascularization, allowing fabrication of large engineered constructs. The network of vascular channels within a frontal-parietal defect in a patient, originating from the anterior branch of the middle meningeal artery, was modeled using computer-aided design (CAD) techniques and subsequently incorporated into polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffolds and implanted into a rat model, with an arteriovenous bundle inserted at the proximal extent of the vascular network. After 3 weeks, scaffolds were elevated as a prefabricated composite tissue-polymer flap and transferred using microsurgical technique. Histological examination of explanted scaffolds revealed vascular ingrowth along patterned channels, with abundant capillary and connective tissue formation throughout experimental scaffolds, while control scaffolds showed only granulation tissue. All prefabricated constructs transferred as free flaps survived and were viable. We term this concept “vascular guidance,” whereby neovascularization is guided through customized channels in a scaffold. Our technique might potentially allow fabrication of much larger tissue-engineered constructs than current technologies allow, as well as allowing tailored construct fabrication with a patient-specific vessel network based on CT scan data and CAD technology.
机译:当前的组织工程技术由于血管支架的不足和细胞支架构建物的灌注而受到限制。通过聚合物支架内的仿生血管通道进行的微结构构图可能诱导新血管形成,从而允许制造大型工程构建体。使用计算机辅助设计(CAD)技术对源自脑膜中动脉前支的患者额叶顶缺损内的血管通道网络进行建模,然后将其并入采用熔融沉积法制备的聚己内酯(PCL)支架中建模(FDM)。将骨髓来源的间充质干细胞(MSC)播种到支架上,并植入大鼠模型,在血管网络的近端插入动静脉束。 3周后,将支架升高为预制的复合组织-聚合物瓣,并使用显微外科技术转移。移植支架的组织学检查显示,血管沿有规律的通道向内生长,在整个实验支架中均具有丰富的毛细血管和结缔组织形成,而对照支架仅显示肉芽组织。以游离皮瓣转移的所有预制结构均存活且可行。我们将这个概念称为“血管引导”,即通过支架中的定制通道引导新血管形成。我们的技术可能潜在地允许制造比当前技术所允许的更大的组织工程构造,并且允许使用基于CT扫描数据和CAD技术的患者特定血管网络来量身定制构造。

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