Exploiting the layer-by-layer nanoarchitectonics for the fabrication of polymer capsules: A toolbox to provide multifunctional properties to target complex pathologies

[EN] Polymer capsules fabricated via the layer-by-layer (LbL) approach have attracted a great deal of attention for biomedical applications thanks to their tunable architecture. Compared to alternative methods, in which the precise control over the final properties of the systems is usually limited, the intrinsic versatility of the LbL approach allows the functionalization of all the constituents of the polymeric capsules following relatively simple protocols. In fact, the final properties of the capsules can be adjusted from the inner cavity to the outer layer through the polymeric shell, resulting in therapeutic, diagnostic, or theranostic (i.e., combination of therapeutic and diagnostic) agents that can be adapted to the particular characteristics of the patient and face the challenges encountered in complex pathologies. The biomedical industry demands novel biomaterials capable of targeting several mechanisms and/or cellular pathways simultaneously while being tracked by minimally invasive techniques, thus highlighting the need to shift from monofunctional to multifunctional polymer capsules. In the present review, those strategies that permit the advanced functionalization of polymer capsules are accordingly introduced. Each of the constituents of the capsule (i.e., cavity, multilayer membrane and outer layer) is thoroughly analyzed and a final overview of the combination of all the strategies toward the fabrication of multifunctional capsules is presented. Special emphasis is given to the potential biomedical applications of these multifunctional capsules, including particular examples of the performed in vitro and in vivo validation studies. Finally, the challenges in the fabrication process and the future perspective for their safe translation into the clinic are summarized.The authors are thankful for funds from the Basque Government, Department of Education (IT-927-16 and PIBA_2021_1_0048)

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

[EN]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 degrees 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.The authors acknowledge financial support from the European Commission through SUSPOL-EJD 642671 project. M.C.A. thanks the University of Birmingham for funding