A bio-inspired hybrid nanosack for graft vascularization at the omentum

用于网膜移植血管化的仿生混合纳米袋

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作者:Patrick T J Hwang, Dong-Jin Lim, Timothy Fee, Grant C Alexander, Ajay Tambralli, Adinarayana Andukuri, Liqun Tian, Wanxing Cui, Joel Berry, Shawn R Gilbert, Ho-Wook Jun

Significance

For three-dimensional tissue engineering scaffolds, the major challenges of hydrogels are poor mechanical integrity and difficulty in handling during implantation. In contrast, electrospun scaffolds provide tunable mechanical properties and high porosity; but, are limited in cell encapsulation. To overcome these limitations, we developed a "hybrid nanosack" by combination of a peptide amphiphile (PA) nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures. This design synergistically possessed the characteristics of both approaches. In this study, the hybrid nanosack was applied to enhance local angiogenesis in the omentum, which is required of tissue engineering scaffolds for graft survival. The hybrid nanosack was implanted into rat omentum for 14days and vascularization was analyzed by micro-CT and immunohistochemistry. We demonstrate that both FGF-2 delivery and porous crater-like structures work synergistically to enhance blood vessel formation within the hybrid nanosack. Therefore, the hybrid nanosack will provide a new strategy for engineering scaffolds to achieve graft survival in the omentum by stimulating local vascularization, thus overcoming the limitations of current strategies.

Statement of significance

For three-dimensional tissue engineering scaffolds, the major challenges of hydrogels are poor mechanical integrity and difficulty in handling during implantation. In contrast, electrospun scaffolds provide tunable mechanical properties and high porosity; but, are limited in cell encapsulation. To overcome these limitations, we developed a "hybrid nanosack" by combination of a peptide amphiphile (PA) nanomatrix gel and an electrospun poly (ε-caprolactone) (ePCL) nanofiber sheet with porous crater-like structures. This design synergistically possessed the characteristics of both approaches. In this study, the hybrid nanosack was applied to enhance local angiogenesis in the omentum, which is required of tissue engineering scaffolds for graft survival. The hybrid nanosack was implanted into rat omentum for 14days and vascularization was analyzed by micro-CT and immunohistochemistry. We demonstrate that both FGF-2 delivery and porous crater-like structures work synergistically to enhance blood vessel formation within the hybrid nanosack. Therefore, the hybrid nanosack will provide a new strategy for engineering scaffolds to achieve graft survival in the omentum by stimulating local vascularization, thus overcoming the limitations of current strategies.

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