Engineering functional microvessels in synthetic polyurethane random-pore scaffolds by harnessing perfusion flow.

Recently reported biomaterial-based approaches toward prevascularizing tissue constructs rely on biologically or structurally complex scaffolds that are complicated to manufacture and sterilize, and challenging to customize for clinical applications. In the current work, a prevascularization method for soft tissue engineering that uses a non-patterned and non-biological scaffold is proposed. Human fibroblasts and HUVECs were seeded on an ionomeric polyurethane-based hydrogel and cultured for 14 days under medium perfusion. A flow rate of 0.05 mL/min resulted in a greater lumen density in the constructs relative to 0.005 and 0.5 mL/min, indicating the critical importance of flow magnitude in establishing microvessels. Constructs generated at 0.05 mL/min perfusion flow were implanted in a mouse subcutaneous model and intravital imaging was used to characterize host blood perfusion through the construct after 2 weeks. Engineered microvessels were functional (i.e. perfused with host blood and non-leaky) and neovascularization of the construct by host vessels was enhanced relative to non-prevascularized constructs. We report on the first strategy toward engineering functional microvessels in a tissue construct using non-bioactive, non-patterned synthetic polyurethane materials.

Electrospun polyurethane nanofiber scaffolds with ciprofloxacin oligomer versus free ciprofloxacin: Effect on drug release and cell attachment.

An electrospun degradable polycarbonate urethane (PCNU) nanofiber scaffold loaded with antibiotic was investigated in terms of antibacterial efficacy and cell compatibility for potential use in gingival tissue engineering. Antimicrobial oligomer (AO), a compound which consists of two molecules of ciprofloxacin (CF) covalently bound via hydrolysable linkages to triethylene glycol (TEG), was incorporated via a one-step blend electrospinning process using a single solvent system at 7 and 15% w/w equivalent CF with respect to the PCNU. The oligomeric form of the drug was used to overcome the challenge of drug aggregation and burst release when antibiotics are incorporated as free drug. Electrospinning parameters were optimized to obtain scaffolds with similar alignment and fiber diameter to non-drug loaded fibers. AO that diffused from the fibers was hydrolysed to release CF slowly and in a linear manner over the duration of the study, whereas scaffolds with CF at the same concentration but in free form showed a burst release within 1h with no further release throughout the study duration. Human gingival fibroblast (HGF) adhesion and spreading was dependent on the concentration and form the CF was loaded (AO vs. free CF), which was attributed in part to differences in scaffold surface chemistry. Surface segregation of AO was quantified using surface-resolved X-ray photoelectron spectroscopy (XPS). These findings are encouraging and support further investigation for the use of AO as a means of attenuating the rapid release of drug loaded into nanofibers. The study also demonstrates through quantitative measures that drug additives have the potential to surface-locate without phase separating from the fibers, leading to fast dissolution and differential fibroblast cell attachment.