A bio-inspired hybrid nanosack for graft vascularization at the omentum.
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 hybrid nanosack 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 ePCL sheet with porous crater-like structures improved cell and blood vessel penetration through the hybrid nanosack. The hybrid nanosack also provided multi-stage fibroblast growth factor-2 (FGF-2) release kinetics for stimulating local angiogenesis. The hybrid nanosack was implanted into rat omentum for 14days and vascularization was analyzed by micro-CT and immunohistochemistry; the data clearly demonstrated 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.



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.
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Patrick T J
PT
Hwang
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Dong-Jin
DJ
Lim
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Timothy
T
Fee
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Grant C
GC
Alexander
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Ajay
A
Tambralli
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Adinarayana
A
Andukuri
Department of Surgery, University of Alabama at Birmingham, AL 35294, USA.
Liqun
L
Tian
Medstar Georgetown Transplant Institute, Medstar Georgetown University Hospital, Washington DC 20007, USA.
Wanxing
W
Cui
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA.
Joel
J
Berry
Department of Surgery, University of Alabama at Birmingham, AL 35294, USA.
Shawn R
SR
Gilbert
Department of Biomedical Engineering, University of Alabama at Birmingham, AL 35294, USA. Electronic address: hwjun@uab.edu.
Ho-Wook
HW
Jun
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D057139:Nanofibers / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009852:Omentum / Q000098:blood supply* / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011091:Polyesters / Q000494:pharmacology; D016062:Porosity; D051381:Rats; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography
D001672:Biocompatible Materials; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011091:Polyesters; D016222:Fibroblast Growth Factor 2; C016240:polycaprolactone
Crater-like structure; Electrospun; Hybrid nanosack; Omentum; Tissue engineering