Pathogenic PRPF8 variants cause severe retinal degeneration, but their biomechanical correlates in the retinal pigment epithelium (RPE) remain poorly characterized. We developed and applied a reconfigured double resonant piezoelectric cytometry (DRPC) platform for label-free mechanophenotyping of patient-derived induced pluripotent stem cell-derived RPE monolayers (iPSC-RPE, iRPE). The DRPC platform enabled real-time estimation of traction-associated surface lateral stress, storage modulus, loss modulus, and loss tangent during monolayer adhesion and maturation. Compared with control iRPE, the patient-derived line carrying the PRPF8 c.5792 C > T variant showed impaired barrier function, downregulation of selected cytoskeletal and contractility-associated genes, a descriptively delayed transition from negative protrusive to positive contractile surface stress, less stable maintenance of positive contractile loading, and different group-mean elastic and dissipative trajectories. These mechanical patterns co-occurred with qualitative differences in F-actin and vinculin organization and reduced integrin α5β1 fluorescence intensity. These findings identify exploratory, variant-associated differences in dynamic mechanical response patterns in the studied patient-derived iRPE line (PRPF8 c.5792 C > T) and support DRPC as a complementary label-free approach for monolayer-scale mechanophenotyping in inherited retinal disease models.
Myocardial infarction (MI) produces coupled structural and biological injury that evolves across overlapping and spatially heterogeneous pathological contexts. Existing reviews have commonly summarized hydrogel material classes, therapeutic cargos, delivery routes, or individual mechanisms, but less attention has been given to translating post-MI pathology into measurable engineering criteria, explicit evidence boundaries, and structured translational requirements. This conceptual narrative review addresses this gap using a pathology-informed engineering framework supported by targeted literature searches in PubMed and the Web of Science Core Collection. The review links pathological and delivery-related challenges to hydrogel design requirements, measurable material properties, therapeutic strategies, and validation endpoints. It organizes the hydrogel design space using orthogonal descriptors of material origin, network behavior, functional attributes, and architecture; compares injectable, patch-based, cellular, extracellular-vesicle, protein, drug, and nucleic-acid delivery strategies; and defines engineering criteria for mechanics, viscoelasticity, injectability, adhesion, degradation, release, electrical function, responsiveness, and biological validation. Mechanistic plausibility, small-animal efficacy, large-animal evidence, first-in-human safety/feasibility, and demonstrated clinical benefit are treated as distinct evidence levels. Advanced multifunctional systems are evaluated through benefit–trade-off–validation relationships, while clinical translation is considered through manufacturing, CMC, device compatibility, safety, clinically meaningful endpoints, and sequential product-development gates. Future cardiac hydrogel development should be context-aware rather than assigned to fixed post-MI stages, quantitatively characterized using method-appropriate measurements, and advanced according to evidence appropriate to the intended use and development phase. Emphasis on minimum sufficient functionality, reproducible evaluation, clinically realistic delivery, manufacturing feasibility, and safety may improve comparison across platforms and help prioritize candidates for further translational development.
Branched C5-dicarboxylates (C5-DCAs), such as itaconate, are high-value platform chemicals with diverse applications in the synthesis of bio-based polymers. In addition to their industrial relevance, itaconate has attracted attention as a key immunomodulatory metabolite. In this study, we demonstrated that Cupriavidus necator can grow on itaconate as its sole carbon source and identified key genes involved in its degradation through targeted deletions. These include multiple functional homologs of itaconate CoA-transferase, itaconyl-CoA hydratase, and (S)-citramalyl-CoA lyase, which collectively mediate itaconate catabolism. We also identified ItcR1, a LysR-type transcriptional regulator, as a key mediator of itaconate-responsive gene expression. Transcriptomic analysis revealed broader transcriptional responses to itaconate, methylsuccinate, and mesaconate, suggesting an expanded role of C5-DCA metabolism. Finally, by expressing a heterologous cis-aconitate decarboxylase, we achieved the autotrophic production of a C5-DCA mixture of methylsuccinate, citramalate, mesaconate, and itaconate from CO2 and hydrogen. These findings provide new insight into branched C5-DCA metabolism in C. necator and advance its development as a chassis for the sustainable production of these industrially relevant compounds from inorganic feedstocks.
Electrical stimulation (ES) is an established therapeutic strategy for nerve injury that regulates neural cell behavior and promotes tissue regeneration. Furthermore, the bio-scaffolds that are sensitive to external stimuli not only influence cell behavior through their inherent properties, but also act as a medium to receive external signals and regulate cell activity. Therefore, using scaffold materials with good electroactivity combined with exogenous ES is a potentially beneficial approach for repairing spinal cord injuries (SCI). In this research, we developed a multifunctional conductive biomimetic scaffold suitable for combined electrical stimulation therapy. Firstly, a biomimetic scaffold material (GelMA) was prepared by combining patterned nanofiber with hydrogel. Then, the stromal cell-derived factor 1 labeled with 3,4-dihydroxyphenylalanine (DOPA) (SDF-1), donepezil (DPL) and two-dimensional titanium carbide-magnesium oxide composite material (MXene-MgO) were loaded onto the surface of the scaffold. MXene-MgO, DOPA modified SDF-1 and DPL endow the scaffold material with excellent electrical conductivity, anti-inflammatory and antibacterial properties, long-term stem cell recruitment function, and the ability to prevent glial scar formation during spinal cord tissue regeneration. Cell and animal experiments showed that under ES, the MXene-MgO/SDF-1/DPL scaffold can effectively enhance the activity of neural stem cells (NSCs), promote the recovery of motor function in rats, and increase the regeneration rate of new neurons. We suggest that this multi-functional bionic scaffold can provide a new treatment strategy for spinal cord injuries, and at the same time expand the application scope of auxiliary therapies such as ES.
Natural polysaccharides are versatile building blocks for regenerative biomaterials because of their structural diversity, generally favorable biocompatibility and biodegradability, chemical tunability, and capacity for biologically relevant interactions. Advances in biotechnology and materials engineering have expanded their role from primarily structural matrices to multifunctional platforms that can influence cellular, immune, and biochemical processes during tissue repair. This review presents an integrated biological engineering framework linking polysaccharide source and molecular architecture with extraction and purification, chemical functionalization, crosslinking, advanced fabrication, biological recognition, and translational performance. Particular emphasis is placed on structure–function relationships, stereospecific glycan–receptor interactions, immune-instructive biomaterials, protein-mediated cell–material interactions, microbiome-responsive systems, and emerging artificial intelligence-assisted approaches for biomaterial design. The importance of material purity is also critically considered, particularly the potential for residual endotoxin contamination to confound interpretation of immunomodulatory responses and compromise reproducibility. Representative applications in skin, musculoskeletal, cardiovascular, neural, and other regenerative systems illustrate how material composition, scaffold architecture, biofunctionalization, and manufacturing strategy collectively influence biological performance. Finally, challenges associated with scalable manufacturing, batch-to-batch reproducibility, sterilization, storage stability, quality control, regulatory translation, and clinical implementation are examined. By integrating molecular design, biological mechanisms, fabrication, and translational requirements, this review provides engineering principles for the development of adaptive polysaccharide biomaterials and identifies priorities for advancing reproducible and clinically translatable regenerative technologies.
