Microstructured Photo-Crosslinked Poly(Trimethylene Carbonate) for Use in Soft Lithography Applications: A Biodegradable Alternative for Poly(Dimethylsiloxane).

Photo-crosslinkable poly(trimethylene carbonate) (PTMC) macromers were used to fabricate microstructured surfaces. Microstructured PTMC surfaces were obtained by hot embossing the macromer against structured silicon masters and subsequent photo-crosslinking, resulting in network formation. The microstructures of the master could be precisely replicated, limiting the shrinkage. Microstructured PTMC was investigated for use in two different applications: as stamping material to transfer a model protein to another surface and as structured substrate for cell culture. Using the flexible and elastic materials as stamps, bovine serum albumin labelled with fluorescein isothiocyanate was patterned on glass surfaces. In cell culture experiments, the behavior of human mesenchymal stem cells on nonstructured and microstructured PTMC surfaces was investigated. The cells strongly adhered to the PTMC surfaces and proliferated well. Compared to poly(dimethylsiloxane) (PDMS), which is commonly used in soft lithography, the PTMC networks offer significant advantages. They show better compatibility with cells, are biodegradable, and have much better mechanical properties. Both materials are transparent, flexible, and elastic at room temperature, but the tear resistance of PTMC networks is much higher than that of PDMS. Thus, PTMC might be an alternative material to PDMS in the fields of biology, medicine, and tissue engineering, in which microfabricated devices are increasingly being applied.

Preparation of a designed poly(trimethylene carbonate) microvascular network by stereolithography.

Designed flexible and elastic network structures are prepared by stereolithography using a photo-crosslinkable resin based on a poly(trimethylene carbonate) (PTMC) macromer with a molecular weight of 3150 g/mol. Physical properties and the compatibility with human umbilical vein endothelial cells (HUVECs) are evaluated. The hydrophobic networks are found to be flexible and elastic, with an E modulus of 7.9 ± 0.1 MPa, a tensile strength of 3.5 ± 0.1 MPa and an elongation at break of 76.7 ± 0.7%. HUVECs attach and proliferate well on the surfaces of the built structures. A three-dimensional microvascular network is designed to serve as a perfusable scaffold for tissue engineering. In the design, 5 generations of open channels each branch into 4 smaller channels yielding a microvascular region with a high density of capillaries. The overall cross-sectional area through which medium or blood can be perfused remains constant. These structures would ensure efficient nourishment of cells in a large volume of tissue. Built by stereolithography using the PTMC resin, the smallest channels of these structures have square cross-sectional areas, with inner widths of approximately 224 µm and wall thicknesses of approximately 152 µm. The channels are open, allowing water to perfuse the scaffold at 0.279 ± 0.006 mL/s at 80 mmHg and 0.335 ± 0.009 mL/s at 120 mmHg.

Flexible and elastic scaffolds for cartilage tissue engineering prepared by stereolithography using poly(trimethylene carbonate)-based resins.

The aim of this study is to investigate the applicability of flexible and elastic poly(trimethylene carbonate) (PTMC) structures prepared by stereolithography as scaffolds for cartilage tissue engineering. A three-armed methacrylated PTMC macromer with a molecular weight of 3100 g mol(-1) is used to build designed scaffolds with a pore diameter of 350 ± 12 µm and a porosity of 54.0 ± 2.2%. Upon seeding of bovine chondrocytes in the scaffolds, the cells adhere and spread on the PTMC surface. After culturing for 6 weeks, also cells with a round morphology are present, indicative of the differentiated chondrocyte phenotype. Sulphated glycosaminoglycans and fibrillar collagens are deposited by the cells. During culturing for 6 weeks, the compression moduli of the constructs increases 50% to approximately 100 kPa.

Preparation of flexible and elastic poly(trimethylene carbonate) structures by stereolithography.

3D porous and non-porous structures are designed and prepared by stereolithography using resins based on PTMC macromers. Tough, flexible network films prepared in this manner show E moduli of ≈3.8 MPa and high elongations at break >900%; tensile strengths are ≈4.2 MPa. These values increase with increasing PTMC macromer molecular weight. To reach suitable viscosities for processing, up to 45 wt% propylene carbonate is added as non-reactive diluent. The solid specimens have compression moduli of 3.1-4.2 MPa, similar to the values determined in tensile testing. The built porous structures show porosities of 53-66% and average pore sizes of 309-407 µm. The compression moduli of the porous structures are significantly lower than those of the solid structures.

Designing porosity and topography of poly(1,3-trimethylene carbonate) scaffolds.

Using phase separation micromolding (PSmicroM) we developed porous micro-patterned sheets from amorphous poly(1,3-trimethylene carbonate) (PTMC). The use of these PTMC sheets can be advantageous in tissue engineering applications requiring highly flexible constructs. Addition of poly(ethylene oxide) (PEO) in various amounts to PTMC casting solutions provides PTMC sheets with tailored porosity and pore sizes in the range 2-20 microm. The pore-forming effect of PEO during the phase separation process is evaluated and glucose transport measurements show that the pores are highly interconnected. Additionally, tailoring the micro-pattern design yields PTMC sheets with various surface topographies. Cell culturing experiments with C2C12 pre-myoblasts revealed that cell attachment and proliferation on these sheets is relatively high and that the micro-pattern topography induces a clearly defined cell organization.