Spatiotemporal control of vascularization and innervation is a desired hallmark in advanced tissue regeneration. For this purpose, we design a 3D model scaffold, based on elastin‐like recombinamer (ELR) hydrogels. This contains two interior and well‐defined areas, small cylinders, with differentiated bioactivities with respect to the bulk. Both are constructed on a protease sensitive ELR with a fast‐proteolyzed domain, but one bears a VEGF‐mimetic peptide (QK) and the other a laminin‐derived pentapeptide (IKVAV), to promote angiogenesis and neurogenesis, respectively. The outer bulk is based on a slow proteolytic sequence and RGD cell adhesion domains. In vitro studies show the effect of QK and IKVAV peptides on the promotion of endothelial cell and axon spreading, respectively. The subcutaneous implantation of the final 3D scaffold demonstrates the ability to spatiotemporally control angiogenesis and neurogenesis in vivo. Specifically, the inner small cylinder containing the QK peptide promotes fast endothelialization, whereas the one with IKVAV peptide promotes fast neurogenesis. Both, vascularization and innervation take place in advance of the bulk scaffold infiltration. This scaffold shows that it is possible to induce vascularization and innervation in predetermined areas of the scaffold well ahead to the bulk infiltration. That significantly increases the efficiency of the regenerative activity.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain the only alternative to producing these compounds on an industrial scale. Their supply can often be implemented with laboratory scale cultures for bacterial, fungal, or microalgal sources. However, a diverse approach, combining traditional methods with modern synthetic biology and biosynthesis strategies, must be considered for invertebrate MNPs, as they are usually naturally accumulated in only very small quantities. This review offers a comprehensive examination of various production strategies for MNPs, addressing the challenges related to supply, synthesis, and scalability. It also underscores recent biotechnological advancements that are likely to transform the current industrial-scale manufacturing methods for pharmaceuticals derived from marine sources.

Despite the remarkable progress in the generation of recombinant elastin-like (ELR) hydrogels, further improvements are still required to enhance and control their viscoelasticity, as well as limit the use of expensive chemical reagents, time-consuming processes and several purification steps. To alleviate this issue, the reactivity of carboxylic groups from glutamic (E) acid distributed along the hydrophilic block of an amphiphilic ELR (coded as E50I60) with amine groups has been studied through a one-pot amidation reaction in aqueous solutions, for the first time. By means of this approach, immediate conjugation of E50I60 with molecules containing amine groups has been performed with a high yield, as demonstrated by the 1H NMR and MALDI-TOF spectroscopies. This has resulted in the preparation of viscoelastic irreversible hydrogels through the "in-situ" cross-linking of E50I60 with another ELR (coded as VKV24) containing amine groups from lysines (K). The rheology analysis demonstrated that the gelation process takes place following a dual mechanism dependent on the ELR concentration: physical cross-linking of I60 block through the hydrophobic interactions, and covalent cross-linking of E50I60 with VKV24 through the amidation reaction. While the chemical network formed between the hydrophilic E50 block and VKV24 ELR preserves the elasticity of ELR hydrogels, the self-assembly of the I60 block through the hydrophobic interactions provides a tunable physical network. The presented investigation serves as a basis for generating ELR hydrogels with tunable viscoelastic properties promising for tissue regeneration, through an "in-situ", rapid, scalable, economically and feasible one-pot method.