para‐Quinone methides (p‐QMs) are naturally occurring molecules that have been finding increasing synthetic applications in the last few years. The presence of two electronically different exocyclic conjugate substituents in their structure, carbonyl and methylidene, leads to a pronounced reactivity owing to the polarization of the molecule. In this sense, those are prone to undergo the attack of nucleophiles in the terminal carbon exocyclic double bond, behaving as vinylogous electrophiles and generating 1,6‐addition products. In this context, in the last few years the development of catalytic approaches for 1,6‐nucleophilic addition reactions involving p‐QMs has attracted considerable attention. Considering the extensive applications that such molecules have found in the last decades in 1,6‐addition reactions, in this review we comprehensively discuss the historical development of this field, starting with early approaches on natural product synthesis, going through seminal non‐stereoselective processes and progressing to cutting‐edge asymmetric‐catalyzed approaches.

Photodynamic inactivation (PDI) is an efficient approach against a wide range of microorganisms and can be viewed as an alternative for the treatment of microbial infections. In this work we synthesized "first" and "second" generation photosensitizers (PSs), the tetra-cationic porphyrin and the new penta-cationic chlorin , respectively, and evaluated their efficiency against two antibiotic resistant bacterial strains, Staphylococcus aureus and Pseudomonas aeruginosa. The PS was obtained in very good yield by an easy synthesis method. The PDI studies were performed in parallel with 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin tetra-iodide (), a widely studied PS in PDI, and the obtained results were compared. Two different light ranges were used: white light (400-800 nm) and red light (530-800 nm) delivered at a fluence rate of 150 mW cm(-2). The results show that both strains, even though antibiotic resistant, were efficiently inactivated by the three PSs, chlorin being the most effective. For the Gram positive bacterium S. aureus a 7.0 log reduction was observed after 5-10 min of irradiation, at a concentration of 0.5 μM, whereas for the Gram negative P. aeruginosa, similar photoinactivation occurred at a higher PS concentration (10 μM) and after a longer irradiation period (30 min). The synthetic chlorin can be regarded as promising for the treatment of bacterial infections under red light, which penetrates deeper in living tissues. The results of this study open the possibility to prepare a new series of chlorin-type derivatives to efficiently photoinactivate Gram (+) and (-) antibiotic resistant bacteria. The efficient PDI with the chlorin indicates high potential for the use of a scaffold in the preparation of new generation PSs based on cationic chlorin derivatives.

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Leveraging 4D biofabrication for engineering biomimetic living constructs is rapidly emerging as a valuable strategy for recapitulating native tissue dynamics, via on‐demand stimuli, or in a naturally evolving mode. Carefully selecting smart materials with suitable responsiveness and cell‐supporting functionalities is crucial to take full operational advantage of this next‐generation technology. Recent endeavors combining naturally available polymers or hybrid smart materials improve the potential to manufacture volumetrically defined, cell‐rich constructs that may display stimuli–responsive properties, shape memory/shape morphing features, and/or dynamic motion in time. In this review, natural origin biomaterials and the stimuli that can be exploited for granting dynamic morphological features and functionalities post‐printing are highlighted. A broad overview of recent reports focusing on 4D‐bioprinted constructs for tissue engineering and regenerative medicine is also provided and critically discussed in light of current challenges, as well as foreseeable advances. It is envisioned that upon assurance of key regulatory demands, such technology will become translatable to numerous biomedical applications that require fabrication of constructs with dynamic functionality.

Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures < 25°C, iii) iron coordination of the hydroxypyridinone (HOPO) moieties at physiological pH, and iv) core liquefaction at 37°C. With the design of a proteolytically degradable shell, the possibility of encapsulating human adipose-derived mesenchymal stem cells (hASC) with and without the presence of polycaprolactone microparticles ( PCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need for PCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.

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Smart polymeric biomaterials have been the focus of many recent biomedical studies, especially those with adaptability to defects and potential to be implanted in the human body. Herein we report a versatile and straightforward method to convert non-thermoresponsive hydrogels into thermoresponsive systems with shape memory ability. As a proof of concept, a thermoresponsive polyurethane mesh was embedded within a methacrylated chitosan (CHTMA), gelatin (GELMA), laminarin (LAMMA) or hyaluronic acid (HAMA) hydrogel network, which afforded hydrogel composites with shape memory ability. With this system, we achieved good to excellent shape fixity ratios (50–90%) and excellent shape recovery ratios (∼100%, almost instantaneously) at body temperature (37 °C). Cytocompatibility tests demonstrated good viability either with cells on top or encapsulated during all shape memory processes. This straightforward approach opens a broad range of possibilities to convey shape memory properties to virtually any synthetic or natural-based hydrogel for several biological and nonbiological applications.

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