Influence of Polymeric Microparticle Size and Loading Concentration on 3D Printing Accuracy and Degradation Behavior of Composite Scaffolds.

Successful employment of 3D printing for delivery of therapeutic biomolecules requires protection of their bioactivity on exposure to potentially inactivating conditions. Although intermediary encapsulation of the biomolecules in polymeric particulate delivery vehicles is a promising strategy for this objective, the inclusion of such particles in 3D printing formulations may critically impact the accuracy or precision of 3D printed scaffolds relative to their intended designed architectures, as well as the degradation behavior of both the scaffolds and the included particles. The present work aimed to elucidate the effect of poly(d,l-lactic-co-glycolic acid) particle size and loading concentration on material accuracy, machine precision, and degradation of 3D printed poly(ɛ-caprolactone)-based scaffolds. Using a main effects analysis, the sizes and loading concentrations of particle delivery vehicles investigated were found to have neither a beneficial nor disadvantageous influence on the metrics of printing quality such as material accuracy and machine precision. Meanwhile, particle loading concentration was determined to influence degradation rate, whereas printing temperature affected the trends in composite weight-average molecular weight. Neither of the two particle-related parameters (concentration nor diameter) was found to exhibit a significant effect on intra-fiber nor inter-fiber porosity. These findings evidence the capacity for controlled loading of particulate delivery vehicles in 3D printed scaffolds while preserving construct accuracy and precision, and with predictable dictation of composite degradation behavior for potential controlled release of encapsulated biomolecules.

Tuning Structural Organization via Molecular Design and Hierarchical Assembly to Develop Supramolecular Thermoresponsive Hydrogels.

The cellular microenvironment is composed of a dynamic hierarchical fibrillar architecture providing a variety of physical and bioactive signals to the surrounding cells. This dynamicity, although common in biology, is a challenge to control in synthetic matrices. Here, responsive synthetic supramolecular monomers were designed that are able to assemble into hierarchical fibrous structures, combining supramolecular fiber formation via hydrogen bonding interactions, with a temperature-responsive hydrophobic collapse, resulting in cross-linking and hydrogel formation. Therefore, amphiphilic molecules were synthesized, composed of a hydrogen bonding ureido-pyrimidinone (UPy) unit, a hydrophobic alkyl spacer, and a hydrophilic oligo(ethylene glycol) tail. The temperature responsive behavior was introduced by functionalizing these supramolecular amphiphiles with a relatively short poly(N-isopropylacrylamide) (PNIPAM) chain (M n ∼ 2.5 or 5.5 kg/mol). To precisely control the assembly of these monomers, the length of the alkyl spacer between the UPy moiety and PNIPAM was varied in length. A robust sol-gel transition, with the dodecyl UPy-PNIPAM molecule, was obtained, with a network elasticity enhancing over 2000 times upon heating above room temperature. The UPy-PNIPAM compounds with shorter alkyl spacers were already hydrogels at room temperature. The sol-gel transition of the dodecyl UPy-PNIPAM hydrogelator could be tuned by the incorporation of different UPy-functionalized monomers. Furthermore, we demonstrated the suitability of this system for microfluidic cell encapsulation through a convenient temperature sol-gel transition. Our results indicate that this novel thermoresponsive supramolecular system offers a modular platform to study and guide single-cell behavior.