Hai Liu

Precise intracellular delivery remains a critical barrier to the efficacy of therapeutic biomolecules. Coacervates, with their high loading capacity, have emerged as a transformative drug delivery platform that can facilitate the intracellular delivery of diverse therapeutic cargos but are limited by poor stability, nonspecific cellular internalization, and uncontrolled release. Herein, we report a simple and versatile surface-engineering strategy that improves the stability of coacervates and enables programmable cell targeting and precise intracellular delivery. Peptide coacervates (PCs) designed with programmable release were coated with polyphenol–peptide networks (PC@PPNs) to encapsulate diverse cargos, including fluorophores, toxic proteins, pro-apoptotic peptides, and plasmid DNA. The dual pH- and glutathione-responsive disassembly of PC@PPNs facilitates endosomal escape and enables controlled cytosolic release. Notably, the association of PC@PPNs with specific cells can be readily programmed by modulating the peptide sequence on PPNs. For example, incorporating HER2-targeting peptides increases the specific association of PC@PPNs with SKOV3 cells from 14% to 75%. The cell-specific targeting is further validated in vivo, as demonstrated by a pronounced size reduction in HER2-overexpressing tumors. This work establishes a rational framework for engineering functional coacervates, advancing their development as versatile and programmable platforms for intracellular delivery.

Severe skin injuries, particularly irregularly shaped deep burns, pose significant clinical challenges due to their complex topography, hypoxic microenvironment, and high susceptibility to infection, leading to prolonged healing processes. In this work, a proof‐of‐concept bioactive facial mask (BFM) is developed that integrates 3D bioprinted, patient‐specific dressing with living microalgae and active therapeutics to promote the regeneration of non‐uniform deep burn wounds. Specifically, multifunctional customized BFM is engineered by embedded bioprinting from alginate‐based bioinks containing oxygen‐generating microalgae, bioactive ions (i.e., SeO ₃ ²⁻ and Zn ²⁺ ), and cell‐proliferating collagen, ensuring its conformal adhesion to the wound region for precise delivery of oxygen and therapeutic agents. The BFM not only alleviated the hypoxia condition by continuous oxygen supply via microalgal photosynthesis, but also scavenged excess reactive oxygen species (ROS), thereby creating a balanced redox environment that promotes cell proliferation and migration. Moreover, BFM significantly accelerated the healing of burn wounds in rats, promoted skin regeneration, and reduced inflammatory responses, restoring 95.8 ± 3.4% of the whole skin structure within 14 days after second‐degree burns. This work offers a customized and versatile strategy for the fabrication of bioactive wound dressing, providing insights for developing living materials for advanced biomedicine.

Providing oxygen and preventing infection at wound sites are effective ways to heal diabetic chronic wounds. Inspired by natural lichens, a bioprinted biogenic hydrogel (BBH) containing microalgae and probiotics is developed for diabetic chronic wound therapeutics, which offers prolonged biogenetic oxygen supply by microalgae and infection inhibition by probiotics. The rational design of symbiotic BBH with customizable structure and microorganism composition enhances wound resilience against elevated glucose levels and hypoxia, leading to the increased migration ability of fibroblasts and the angiogenic potential of human umbilical vein endothelial cells. Notably, BBH‐treated diabetic wounds exhibit dense vascular distribution, reduced hypoxia levels and inflammatory responses, and enhanced epithelial differentiation and keratinization abilities. Consequently, the BBH achieves rapid tissue repairing within 3 d and restores approximately 90% of the whole skin structure within 12 d. This work presents an engineered platform for regulating biological microenvironment of diabetic wounds and provides insights for developing bioprinted hybrid microorganism systems.

This review provides a guideline for the rational design of metal–phenolic network (MPN) composites—which are fabricated from MPN and one or more functional components ( e.g. , drugs, proteins)—for various applications across diverse disciplines.

Photosynthetic microalgae produce valuable metabolites and are a source of sustainable food that supports life without compromising arable land. However, the light self‐shading, excessive water supply, and insufficient space utilization in microalgae farming have limited its potential in the inland areas most in need of regenerative food solutions. Herein, this work develops a 3D polysaccharide‐based hydrogel scaffold for vertically farming microalgae without needing liquid media. This liquid‐free strategy is compatible with diverse microalgal species and enables the design of living microalgal frameworks with customizable architectures that enhance light and water utilization. This approach significantly increases microalgae yield per unit water consumption, with an 8.8‐fold increase compared to traditional methods. Furthermore, the dehydrated hydrogels demonstrate a reduced size and weight (≈70% reduction), but readily recover their vitality upon rehydration. Importantly, valuable natural products can be produced in this system including proteins, carbohydrates, lipids, and carotenoids. This study streamlines microalgae regenerative farming for low‐carbon biomanufacturing by minimizing light self‐shading, relieving water supply, and reducing physical footprints, and democratizing access to efficient aquatic food production.

Periodontitis, a complex inflammatory disease initiated by bacterial infections, presents a significant challenge in public health. The increased levels of reactive oxygen species and the subsequent exaggerated immune response associated with periodontitis often lead to alveolar bone resorption and tooth loss. Herein, we develop multifunctional metal-phenolic composites (i.e., Au@MPN-BMP2) to address the complex nature of periodontitis, where gold nanoparticles (AuNPs) are coated by metal-phenolic networks (MPNs) and bone morphogenetic protein 2 (BMP2). In this design, MPNs exhibit remarkable antibacterial and antioxidant properties, and AuNPs and BMP2 promote osteogenic differentiation of bone marrow mesenchymal stem cells under inflammatory conditions. In a rat model of periodontitis, treatment with Au@MPN-BMP2 leads to notable therapeutic outcomes, including mitigated oxidative stress, reduced progression of inflammation, and the significant prevention of inflammatory bone loss. These results highlight the multifunctionality of Au@MPN-BMP2 nanoparticles as a promising therapeutic approach for periodontitis, addressing both microbial causative factors and an overactivated immune response. We envision that the rational design of metal-phenolic composites will provide versatile nanoplatforms for tissue regeneration and potential clinical applications.

Synthetic cell exoskeletons created from abiotic materials have attracted interest in materials science and biotechnology, as they can regulate cell behavior and create new functionalities. Here, a facile strategy is reported to mimic microalgal sporulation with on‐demand germination and locomotion via responsive metal–phenolic networks (MPNs). Specifically, MPNs with tunable thickness and composition are deposited on the surface of microalgae cells via one‐step coordination, without any loss of cell viability or intrinsic cell photosynthetic properties. The MPN coating keeps the cells in a dormant state, but can be disassembled on‐demand in response to environmental pH or chemical stimulus, thereby reviving the microalgae within 1 min. Moreover, the artificial sporulation of microalgae resulted in resistance to environmental stresses (e.g., metal ions and antibiotics) akin to the function of natural sporulation. This strategy can regulate the life cycle of complex cells, providing a synthetic strategy for designing hybrid microorganisms.

Polymeric spherulites are typically formed by melt crystallization: spherulitic growth in solution is rare and requires complex polymers and dilute solutions. Here, we report the mild and unique formation of luminescent spherulites at room temperature via the simple molecule benzene-1,4-dithiol (BDT). Specifically, BDT polymerized into oligomers (PBDT) via disulfide bonds and assembled into uniform supramolecular nanoparticles in aqueous buffer; these nanoparticles were then dissolved back into PBDT in a good solvent (i.e., dimethylformamide) and underwent chain elongation to form spherulites (rPBDT) in 10 min. The spherulite geometry was modulated by changing the PBDT concentration and reaction time. Due to the step-growth polymerization and reorganization of PBDT, these spherulites not only exhibited robust structure but also showed broad clusterization-triggered emission. The biocompatibility and efficient cellular uptake of the spherulites further underscore their value as traceable drug carriers. This system provides a new pathway for designing versatile superstructures with value for hierarchical assembly of small molecules into a complicated biological system.

Protocells have garnered considerable attention from cell biologists, materials scientists, and synthetic biologists. Phase-separating coacervate microdroplets have emerged as a promising cytomimetic model because they can internalize and concentrate components from dilute surrounding environments. However, the membrane-free nature of such coacervates leads to coalescence into a bulk phase, a phenomenon that is not representative of the cells they are designed to mimic. Herein, we develop a membranized peptide coacervate (PC) with oppositely charged oligopeptides as the molecularly crowded cytosol and a metal-phenolic network (MPN) coating as the membrane. The hybrid protocell efficiently internalizes various bioactive macromolecules (e.g., bovine serum albumin and immunoglobulin G) (>90%) while also resisting radicals due to the semipermeable cytoprotective membrane. Notably, the resultant PC@MPNs are capable of anabolic cascade reactions and remain in discrete protocellular populations without coalescence. Finally, we demonstrate that the MPN protocell membrane can be postfunctionalized with various functional molecules (e.g., folic acid and fluorescence dye) to more closely resemble actual cells with complex membranes, such as recognition molecules, which allows for drug delivery. This membrane-bound cytosolic protocell structure paves the way for innovative synthetic cells with structural and functional complexity.