The Rheology of PEOT/PBT Block Copolymers in the Melt State and in the Thermally-Induced Sol/Gel Transition. Implications on the 3D-Printing Bio-Scaffold Process.

Poly(ethyleneoxideterephthalate)/poly(butyleneterephthalate) (PEOT/PBT) segmented block copolymers are widely used for the manufacturing of 3D-printed bio-scaffolds, due to a combination of several properties, such as cell viability, bio-compatibility, and bio-degradability. Furthermore, they are characterized by a relatively low viscosity at high temperatures, which is desired during the injection stages of the printing process. At the same time, the microphase separated morphology generated by the demixing of hard and soft segments at intermediate temperatures allows for a quick transition from a liquid-like to a solid-like behavior, thus favoring the shaping and the dimensional stability of the scaffold. In this work, for the first time, the rheology of a commercial PEOT/PBT material is studied over a wide range of temperatures encompassing both the melt state and the phase transition regime. Non-isothermal viscoelastic measurements under oscillatory shear flow allow for a quantitative determination of the material processability in the melt state. Additionally, isothermal experiments below the order⁻disorder temperature are used to determine the temperature dependence of the phase transition kinetics. The importance of the rheological characterization when designing the 3D-printing scaffold process is also discussed.

Synthetic Biodegradable Hydrogels with Excellent Mechanical Properties and Good Cell Adhesion Characteristics Obtained by the Combinatorial Synthesis of Photo-Cross-Linked Networks.

Major drawbacks of synthetic hydrogels are their poor mechanical properties and their limited ability to allow cell attachment and proliferation. By photo-cross-linking mixtures of dimethacrylate-functionalized oligomers (macromers) in a combinatorial manner in solution, synthetic hydrogels with high water uptake and the remarkable ability to promote cell adhesion and proliferation were prepared. A total of 255 different networks based on poly(trimethylene carbonate) (PTMC)-, poly(d,l-lactide) (PDLLA)-, poly(ε-caprolactone) (PCL)- and poly(ethylene glycol) (PEG) macromers were synthesized simultaneously and screened for their ability to allow the adhesion of human mesenchymal stem cells (hMSCs) in a high throughput-like manner. Of these networks, several hydrogels could be identified that were able to take up large amounts of water while at the same time allowed the adhesion of cells. By synthesizing these hydrogel networks anew and analyzing the cell adhesion and proliferation behavior of human mesenchymal stem cells to these synthetic hydrogels in more detail, it was confirmed that mixed-macromer hydrogel networks prepared from equal amounts of PTMC-dMA 4k, PDLLA-dMA 4k, PCL-dMA 4k, PEG-dMA 4k, and PEG-dMA 10k and hydrogel networks prepared from PTMC-dMA 4k, PDLLA 4k, PEG-dMA 4k, PTMC-dMA 10k and PEG-dMA 10k were highly hydrophilic (water uptake was respectively 181 ± 2 and 197 ± 18 wt % water) and allowed very good cell adhesion and proliferation. Furthermore, these networks were extremely resilient in the hydrated state, with tearing energies of respectively 0.64 ± 0.34 and 0.27 ± 0.04 kJ/m(2). This is much higher than other synthetic hydrogels described in literature and close to articular cartilage (1 kJ/m(2)).

Tough biodegradable mixed-macromer networks and hydrogels by photo-crosslinking in solution.

The preparation of polymeric networks that are both tough and biodegradable remains a challenge. Here we show a very straightforward method to produce tough biodegradable networks from low molecular weight macromers for applications such as tissue engineering. Photo-crosslinking combinatorial mixtures of methacrylate-functionalized poly(1,3-trimethylene carbonate) (PTMC), poly(d,l-lactide) (PDLLA), poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) oligomers in propylene carbonate (PC) allowed the preparation of network films with excellent tensile characteristics and resistance to tearing. This method enabled the production of both very tough mixed-macromer elastomers as well as mixed-macromer hydrogels. A mixed-macromer hydrogel prepared from 33wt.% PTMC, 33wt.% PCL and 33wt.% PEG had a very high tearing energy of 0.81kJ/m(2), which is comparable to tearing energies determined for articular cartilage.

A Combinatorial Photocrosslinking Method for the Preparation of Porous Structures with Widely Differing Properties.

A novel method for the simultaneous preparation of a large number of porous polymeric structures with highly differing physical properties is developed. Low molecular weight methacrylate end-functionalized polymers (macromers) are dissolved in ethylene carbonate, cooled to below the melting temperature of the solvent, and subsequently photocrosslinked. The crystallized and phase-separated ethylene carbonate is extracted with water, upon which a porous crosslinked polymer network is obtained. The method is applied to combinatorial mixtures of methacrylate end-functionalized polymers that are relevant in the biomedical field: poly(trimethylene carbonate-dimethacrylate), poly(D,L-lactide-dimethacrylate), and poly(ethylene glycol-dimethacrylate) dissolved in ethylene carbonate at concentrations of approximately 25 wt%. In this manner, 63 different porous polymeric structures with a very wide range of physical properties are prepared simultaneously. In the hydrated state the compressive moduli of the prepared structures range from 0.01 to 60 MPa, as water uptake ranges between 3 and 1500 wt%.

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.

Combinatorial synthesis of photo-crosslinked biodegradable networks.

PURPOSE: Photo-crosslinking is a technique that can accelerate the development of novel polymeric biomaterials. METHODS: Here we show the development of a combinatorial platform to synthesize numerous synthetic biodegradable and biocompatible networks by photo-crosslinking mixtures of macromers. RESULTS: Combinations of dimethacrylate-terminated macromers based on hydrophobic D,L-lactide (DLLA), trimethylene carbonate (TMC), epsilon-caprolactone (CL), and hydrophilic polyethylene glycol (PEG) were crosslinked into polymer networks with widely differing properties. The interaction of cells with the network surfaces was assessed by an in vitro cell seeding experiment in which cell proliferation was assessed using a DNA proliferation assay. CONCLUSIONS: In this way, a hydrophilic material was identified that unexpectedly supported the proliferation of cells very well.