Tailoring the degradation kinetics of poly(ester carbonate urethane)urea thermoplastic elastomers for tissue engineering scaffolds

Abstract

Biodegradable elastomeric scaffolds are of increasing interest for applications in soft tissue repair and regeneration, particularly in mechanically active settings. The rate at which such a scaffold should degrade for optimal outcomes, however, is not generally known and the ability to select from similar scaffolds that vary in degradation behavior to allow such optimization is limited. Our objective was to synthesize a family of biodegradable polyurethane elastomers where partial substitution of polyester segments with polycarbonate segments in the polymer backbone would lead to slower degradation behavior. Specifically, we synthesized poly(ester carbonate)urethane ureas (PECUUs) using a blended soft segment of poly(caprolactone) (PCL) and poly(1,6-hexamethylene carbonate) (PHC), a 1,4-diisocyanatobutane hard segment and chain extension with putrescine. Soft segment PCL/PHC molar ratios of 100/0, 75/25, 50/50, 25/75, and 0/100 were investigated. Polymer tensile strengths varied from 14 to 34 MPa with breaking strains of 660-875%, initial moduli of 8-24 MPa and 100% recovery after 10% strain. Increased PHC content was associated with softer, more distensible films. Scaffolds produced by salt leaching supported smooth muscle cell adhesion and growth in vitro. PECUU in aqueous buffer in vitro and subcutaneous implants in rats of PECUU scaffolds showed degradation slower than comparable poly(ester urethane)urea and faster than poly(carbonate urethane)urea. These slower degrading thermoplastic polyurethanes provide opportunities to investigate the role of relative degradation rates for mechanically supportive scaffolds in a variety of soft tissue repair and reconstructive procedures.

Figure 1

Synthetic scheme for poly(ester carbonate urethane)ureas.

Figure 2

FT-IR spectra of PEUU, PECUUs and PCUU.

Figure 3

Typical stress-strain curves for PEUU, PECUUs and PCUU films.

Figure 4

(A) Mass remaining and (B) residual inherent viscosity of PEUU, PECUUs and PCUU films after PBS immersion at 37°C over a period of 8 wks. Error bars are only shown for the last time points for clarity. * = reduced inherent viscosity relative to time = 0 (p<0.05).

Figure 5

(A) Metabolic index to show RSMC behavior at 2, 3 and 4 d after cell seeding on PEUU, PECUUs and PCUU films (TCPS as control). Fluorescently stained RSMCs on the surface of a representative PECUU 50/50 film at (B) 2 and (C) 4 d of culture. Other surfaces were comparable. Alpha-smooth muscle actin is stained red with rhodamine phoallidin and cell nuclei are stained blue with DRAQ5. Scale bar = 100 μm.

Figure 6

Electron micrographs of scaffold cross sections generated from (A) PEUU, (B) PECUU 75/25, (C) PECUU 50/50, (D) PECUU 25/75 and (E) PCUU using salt-leaching with salt particles ranging from 100 to 150 μm.

Figure 7

(A) Metabolic index for RSMCs within PEUU, PECUU and PCUU scaffolds after 1 and 7 d spinner flask culture. H&E stained cross-sections of a representative PECUU 50/50 scaffold after (B) 1 and (C) 7 d spinner flask culture. Other scaffolds appeared similar. Scale bar = 100 μm.

Figure 8

Macroscopic view of rat subcutaneous implant sites for (A) PEUU, (B) PECUU 50/50 and (C) PCUU scaffolds after 8 wk. H&E stained cross-sections of the implanted area at 8 wk for (D) PEUU, (E) PECUU 50/50 and (F) PCUU scaffolds demonstrating the variable resorption behavior between scaffold types. Scale bar (A-C) = 5 mm and scale bar (D-F) = 200 μm. Blue arrows indicate suture area which was utilized along the scaffold edge to affix at the time of implantation.