Fabrication of New Hybrid Scaffolds for in vivo Perivascular Application to Treat Limb Ischemia

Michele Carrabba*, Eva Jover Garcia, Marco Fagnano, Anita C Thomas, Elisa Avolio, Thomas D L Richardson, Ben Carter, Giovanni Vozzi, Adam W Perriman, Paolo R Madeddu

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)
66 Downloads (Pure)

Abstract

Cell therapies are emerging as a new therapeutic frontier for the treatment of ischemic disease. However, femoral occlusions can be challenging environments for effective therapeutic cell delivery. In this study, cell-engineered hybrid scaffolds are implanted around the occluded femoral artery and the therapeutic benefit through the formation of new collateral arteries is investigated. First, it is reported the fabrication of different hybrid “hard-soft” 3D channel-shaped scaffolds comprising either poly(ε-caprolactone) (PCL) or polylactic-co-glycolic acid (PLGA) and electro-spun of gelatin (GL) nanofibers. Both PCL-GL and PLGA-GL scaffolds show anisotropic characteristics in mechanical tests and PLGA displays a greater rigidity and faster degradability in wet conditions. The resulting constructs are engineered using human adventitial pericytes (APCs) and both exhibit excellent biocompatibility. The 3D environment also induces expressional changes in APCs, conferring a more pronounced proangiogenic secretory profile. Bioprinting of alginate-pluronic gel (AG/PL), containing APCs and endothelial cells, completes the hybrid scaffold providing accurate spatial organization of the delivered cells. The scaffolds implantation around the mice occluded femoral artery shows that bioengineered PLGA hybrid scaffold outperforms the PCL counterpart accelerating limb blood flow recovery through the formation arterioles with diameters >50 μm, demonstrating the therapeutic potential in stimulating reparative angiogenesis.
Original languageEnglish
Article number598890
Number of pages17
JournalFrontiers in Cardiovascular Medicine
Volume7
DOIs
Publication statusPublished - 19 Nov 2020

Keywords

  • tissue engineering
  • angiogenesis
  • adventitial pericytes
  • hybrid scaffold
  • biomaterials
  • bioprinting
  • electrospinning

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