Abstract

In this study, it was demonstrated that ice-templating via freeze drying with custom-made moulds, in combination with air brushing, allows for the fabrication of poly(glycerol sebacate urethane) (PGSU) scaffolds with hierarchical multilayer microstructures to replicate various native soft tissues. The PGSU scaffolds were either monolayered but exhibited an anisotropic microstructure, or bilayered and trilayered, with each layer showing different microstructures. By using freeze drying with custom-made moulds, the ice crystals of the solvent were grown unidirectionally, and after freeze-drying, the scaffolds had an anisotropic microstructure, mimicking tissues such as tendon and skeletal muscle. The anisotropic PGSU scaffolds were also examined for their tensile strength, and a range of mechanical properties were obtained by altering the reactants’ molar ratio and polymer concentration. This is of importance, since soft tissues exhibit different mechanical properties depending on their native location and functionality. By combining freeze drying with airbrushing, scaffolds were fabricated with a thin, non-porous layer on top of the porous layers to allow three-dimensional cell co-culture for tissues such as skin and oral mucosa. These results show that fabrication techniques can be combined to produce PGSU scaffolds with tailored hierarchical microstructures and mechanical properties for multiple tissue engineering applications.

Highlights

  • Tissue engineering (TE) scaffolds temporarily provide the cells with a three-dimensional (3D) structure until the cells produce their own extracellular matrix (ECM) to replace the scaffold

  • The poly(glycerol sebacate urethane) (PGSU)-parallel scaffold showed no significant difference in pore size between the top, cross- and bottom sections, and its pore sizes ranged from 67.8 ± 20.0 μm to 78.8 ± 24.2 μm

  • Combining freeze drying with custom-made ice-templating moulds with or without airbrushing, scaffolds can be produced with complex, hierarchical, multilayer structures with different pore structures, pore sizes and porosities

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Summary

Introduction

Tissue engineering (TE) scaffolds temporarily provide the cells with a three-dimensional (3D) structure until the cells produce their own extracellular matrix (ECM) to replace the scaffold. Scaffolds should mimic the native 3D ECM structure to guide cell growth in a specific direction and be produced in a reproducible and inexpensive manner. The scaffold microstructure is characterised by its porosity, pore size, pore shape, interconnectivity and orientation. Each of these parameters influences the physical properties (e.g., mechanical properties and degradation rate) and biological properties (e.g., cell proliferation, cell differentiation, collagen production and angiogenesis), and control the growth of the new tissue [2]. By controlling the ice crystal growth during the freezing of the solution, the microstructure of the scaffold can be designed and manufactured to mimic the ECM of native tissues, a process called ice-templating ( known as modified thermal induced phase separation)

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