Triggerable Degradation of Polyurethanes for Tissue Engineering Applications

Abstract

Tissue engineered and bioactive scaffolds with different degradation rates are required for the regeneration of diverse tissues/organs. To optimize tissue regeneration in different tissues, it is desirable that the degradation rate of scaffolds can be manipulated to comply with various stages of tissue regeneration. Unfortunately, the degradation of most degradable polymers relies solely on passive controlled degradation mechanisms. To overcome this challenge, we report a new family of reduction-sensitive biodegradable elastomeric polyurethanes containing various amounts of disulfide bonds (PU-SS), in which degradation can be initiated and accelerated with the supplement of a biological product: antioxidant-glutathione (GSH). The polyurethanes can be processed into films and electrospun fibrous scaffolds. Synthesized materials exhibited robust mechanical properties and high elasticity. Accelerated degradation of the materials was observed in the presence of GSH, and the rate of such degradation depends on the amount of disulfide present in the polymer backbone. The polymers and their degradation products exhibited no apparent cell toxicity while the electrospun scaffolds supported fibroblast growth in vitro. The in vivo subcutaneous implantation model showed that the polymers prompt minimal inflammatory responses, and as anticipated, the polymer with the higher disulfide bond amount had faster degradation in vivo. This new family of polyurethanes offers tremendous potential for directed scaffold degradation to promote maximal tissue regeneration.

Keywords: biodegradation; polyurethane; reduction-sensitive; scaffolds; tissue engineering; triggerable.

Figure 1.

Schematic synthesis of biodegradable polyurethane containing disulfide bonds (PU-SS).

Figure 2.

FT-IR spectra of PU-SS polymers.

Figure 3.

Cyclic stretch of PU-SS films at 30% and 300% deformation.

Figure 4.

Polymer film degradation. (A) Mass remaining of PU-SS films in PBS and 10 mM GSH at 37 °C. (B) Inherent viscosity, (C) Tensile strength and (D) initial modulus changes of polymer films with degradation in GSH. *represented significant different groups (p<0.05).

Figure 5.

Cytotoxicity of polymer degradation products and cell growth on polymer films. (A) Metabolic index of 3T3 fibroblasts cultured with medium mixed with PU-SS degradation products at 0.1 mg/mL. DMEM culture medium was a control. (B) Metabolic index of 3T3 fibroblast seeded on PU-SS films (TCPS as a control) at days 1, 3 and 5. *represented significant different groups (p<0.05).

Figure 6.

Electrospun fibrous morphology of PU-SS scaffolds. (A) PU-BDO, (B) PU-0.5SS, (C) PU-1SS, (D) PU-1.5SS, and (E) PU-1.8SS.

Figure 7.

Cyclic stretch of PU-SS fibrous scaffolds at 30% deformation.

Figure 8.

Scaffold degradation. (A) Mass remaining of fibrous scaffolds in GSH and PBS at 37°C. (B) Scaffold controllable degradation. Scaffolds were immersed in PBS for 14 d and then in 10 mM GSH for another 14 d. (C) PU-BDO, (D) PU-0.5SS, (E) PU-1SS, (F) PU-1.5SS and (G) PU-1.8SS scaffold morphology after 14 d immersion in 10 mM GSH solution. *represented significant different groups (p<0.05).

Figure 9.

Cell growth on scaffolds. (A) Metabolic index to show the 3T3 fibroblast viability on the scaffold (TCPS as a control). SEM micrographs of 3T3 fibroblasts on the surface of PU-1SS scaffold at (B) 1 d, (C) 3 d, and (D) 5 d. *represented significant different groups (p<0.05).

Figure 10.

Histological evaluation of explanted scaffolds in a mouse subcutaneous model. (A) H&E staining were carried out on the scaffolds implanted in mice for 1 and 2 months. Red arrows indicate location of inflammatory cells at the tissue:implant interfaces. (B) Explanted scaffold thicknesses were measured after 1 and 2 month implantation. *: p<0.05, PU-1.8SS compared with other groups at 1 month and 2 month.