A Single Amino Acid Able to Promote High-Temperature Ring-Opening Polymerization by Dual Activation.

Amino acids are indispensable compounds in the body, performing several biological processes that enable proper functioning. In this work, it is demonstrated that a single amino acid, taurine, is also able to promote the ring-opening polymerization (ROP) of several cyclic monomers under industrially relevant conditions. It is shown that the unique zwitterionic structure of taurine, where the negatively charged sulfonic acid group and the protonated amine group are separated by two methylene groups, not only provides high thermal stability but also leads to a dual activation mechanism, which is corroborated by quantum mechanical calculations. This unique mechanism allows for the synthesis of polylactide of up to 50 kDa in bulk at 180 °C with good end-group fidelity using a highly abundant catalyst. Furthermore, cytotoxicity tests confirm that PLLA synthesized with taurine is non-toxic. Moreover, it is demonstrated that the presence of taurine does not have any detrimental effect on the thermal stability of polylactide, and therefore polymers can be used directly without any post-polymerization purification. It is believed that the demonstration that a simple structure composed of a single amino acid can promote polymerization can bring a paradigm shift in the preparation of polymers.

Self-assembled three-dimensional hydrogels based on graphene derivatives and cerium oxide nanoparticles: scaffolds for co-culture of oligodendrocytes and neurons derived from neural stem cells.

Stem cell-based therapies have shown promising results for the regeneration of the nervous system. However, the survival and integration of the stem cells in the neural circuitry is suboptimal and might compromise the therapeutic outcomes of this approach. The development of functional scaffolds capable of actively interacting with stem cells may overcome the current limitations of stem cell-based therapies. In this study, three-dimensional hydrogels based on graphene derivatives and cerium oxide (CeO2) nanoparticles are presented as prospective supports allowing neural stem cell adhesion, migration and differentiation. The morphological, mechanical and electrical properties of the resulting hydrogels can be finely tuned by controlling several parameters of the self-assembly of graphene oxide sheets, namely the amount of incorporated reducing agent (ascorbic acid) and CeO2 nanoparticles. The intrinsic properties of the hydrogels, as well as the presence of CeO2 nanoparticles, clearly influence the cell fate. Thus, stiffer adhesion substrates promote differentiation to glial cell lineages, while softer substrates enhance mature neuronal differentiation. Remarkably, CeO2 nanoparticle-containing hydrogels support the differentiation of neural stem cells to neuronal, astroglial and oligodendroglial lineage cells, promoting the in vitro generation of nerve tissue grafts that might be employed in neuroregenerative cell therapies.

Crystallization-Induced Gelling as a Method to 4D Print Low-Water-Content Non-isocyanate Polyurethane Hydrogels.

The use of three-dimensional (3D) printable hydrogels for biomedical applications has attracted considerable attention as a consequence of the ability to precisely define the morphology of the printed object, allowing patients' needs to be targeted. However, the majority of hydrogels do not possess suitable mechanical properties to fulfill an adequate rheological profile for printability, and hence, 3D printing of cross-linked networks is challenging and normally requires postprinting modifications to obtain the desired scaffolds. In this work, we took advantage of the crystallization process of poly(ethylene glycol) to print non-isocyanate poly(hydroxyurethane) hydrogels with tunable mechanical properties. As a consequence of the crystallization process, the hydrogel modulus can be tuned up to 3 orders of magnitude upon heating up to 40 °C, offering an interesting strategy to directly 3D-print hydrogels without the need of postprinting cross-linking. Moreover, the absence of any toxicity makes these materials ideal candidates for biomedical applications.

Smart Layer-by-Layer Polymeric Microreactors: pH-Triggered Drug Release and Attenuation of Cellular Oxidative Stress as Prospective Combination Therapy.

Polymer capsules fabricated via the layer-by-layer (LbL) approach have emerged as promising biomedical systems for the release of a wide variety of therapeutic agents, owing to their tunable and controllable structure and the possibility to include several functionalities in the polymeric membrane during the fabrication process. However, the limitation of the capsules with a single functionality to overcome the challenges involved in the treatment of complex pathologies denotes the need to develop multifunctional capsules capable of targeting several mediators and/or mechanisms. Oxidative stress is caused by the accumulation of reactive oxygen species [e.g., hydrogen peroxide (H2O2), hydroxyl radicals (•OH), and superoxide anion radicals (•O2-)] in the cellular microenvironment and is a key modulator in the pathology of a broad range of inflammatory diseases. The disease microenvironment is also characterized by the presence of proinflammatory cytokines, increased levels of matrix metalloproteinases, and acidic pH, all of which could be exploited to trigger the release of therapeutic agents. In the present work, multifunctional capsules were fabricated via the LbL approach. Capsules were loaded with an antioxidant enzyme (catalase) and functionalized with a model drug (doxorubicin), which was conjugated to an amine-containing dendritic polyglycerol through a pH-responsive linker. These capsules efficiently scavenge H2O2 from solution, protecting cells from oxidative stress, and release the model drug in acidic microenvironments. Accordingly, in this work, a polymeric microplatform is presented as an unexplored combinatorial approach applicable for multiple targets of inflammatory diseases, in order to perform controlled spatiotemporal enzymatic reactions and drug release in response to biologically relevant stimuli.