Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization

Abstract

Biodegradable synthetic matrices that resemble the size scale, architecture and mechanical properties of the native extracellular matrix can be fabricated through electrospinning. Tubular conduits may also be fabricated with properties appropriate for vascular tissue engineering. Achieving large cell infiltrate within the electrospun matrix in vitro remains time consuming and challenging. This difficulty was overcome by electrospraying smooth muscle cells concurrently with electrospinning of a biodegradable, elastomeric poly(ester urethane)urea (PEUU) small diameter conduit. Constructs were cultured statically or in spinner flasks. Hematoxylin and eosin (H&E) staining demonstrated qualitatively uniform SMC integration radially and circumferentially within the conduit after initial static culture. In comparison with static culture, samples cultured in spinner flasks indicated 2.4 times more viable cells present from MTT and significantly larger numbers of SMCs spread within the electrospun fiber networks by H&E image analysis. Conduits were strong and flexible with mechanical behaviors that mimicked those of native arteries, including static compliance of 1.6 ± 0.5 × 10 −3 mmHg −1 , dynamic compliance of 8.7 ± 1.8 × 10 −4 mmHg −1 , burst strengths of 1750 ± 220 mmHg, and suture retention. This method to rapidly and efficiently integrate cells into a strong, compliant biodegradable tubular matrix represents a significant achievement as a tissue engineering approach for blood vessel replacement.

The Use of Natural Polymers in Tissue Engineering: A Focus on Electrospun Extracellular Matrix Analogues

“…Some of the collection schemes currently used include a single ground, rotating single ground, dual bar, dual ring, single horizontal ring, electrospinning in vitro onto cells [15,17], electrospinning cells simultaneously with polymer (microintegration) [18], or using a rotating electrode airgap collection method [19]. The microintegration process developed by Stankus et al [18] used the principle of electrospraying, a historical precursor to electrospinning, to disperse small charged droplets of cell suspension onto a target simultaneously collecting electrospun fibers. This process had no adverse effect on the cells, and proved to be a viable method for creating a cellularized structure primed for regeneration.…”

Tissue Engineering for Tissue and Organ Regeneration

“…(Stankus, 2007) By concurrent electrospraying and electrospinning of vascular smooth muscle cells and PEUU, respectively, a tubular conduit containing the cells was formed with uniform cellular distribution in a radial and circumferential manner. Further testing revealed the ability of the material to remain sutured, while maintaining compliancy that was similar to native arteries.…”

Electrospray Production of Nanoparticles for Drug/Nucleic Acid Delivery

“…Combined with electrospinning, electrospray was used to fabricate smooth muscle cell integrated blood vessel constructs. (Stankusa et al 2007) In the area of drug/nucleic acid delivery, many biological materials, such as DNA, proteins, and lipids have been electrosprayed without changing their biological activity (Pareta et al 2005;Jayasinghe et al 2005;Davies et al 2005;Wu et al 2009aWu et al , 2009bWu et al , 2010Wu et al , 2011. Proteins, such as bovine serum albumin, have been encapsulated in biodegradable polymeric microcapsules (Pareta and Edirisinghe, 2006;Xie & Wang, 2006), and small molecule drugs, such as taxol and griseofulvin, have been encapsulated in polymeric microparticles for systemic or oral delivery.…”