Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-co-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity.

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects.

Three-dimensional imaging and analysis of pathological tissue samples with de novo generation of citrate-based fluorophores.

Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.

Guanidine cyclic diimides and their polymers.

We report the formation and degradation of a unique guanidine cyclic diimide (GCDI) structure and GCDI-based polymers. The GCDI structure is readily formed under mild conditions. The X-ray crystal structure showed that the delocalized π-orbitals in the guanidine plane are significantly disrupted in the GCDI structure. Unlike amine-based imides, the GCDI structure readily degrades into the initial guanidine in protic solvents at ambient temperatures. Furthermore, poly(GCDI)s, a new category of polymers with the GCDI backbones, can be synthesized from guanidines and dianhydrides. Similar to the monomeric GCDIs, poly(GCDI)s are degraded in protic solvents unlike polyimides with high chemical stability.

Scalable and Isotropic Expansion of Tissues with Simply Tunable Expansion Ratio.

Tissue expansion techniques physically expand swellable gel-embedded biological specimens to overcome the resolution limit of light microscopy. As the benefits of expansion come at the expense of signal concentration, imaging volume and time, and mechanical integrity of the sample, the optimal expansion ratio may widely differ depending on the experiment. However, existing expansion methods offer only fixed expansion ratios that cannot be easily adjusted to balance the gain and loss associated with expansion. Here, a hydrogel conversion-based expansion method is presented, that enables easy adjustment of the expansion ratio for individual needs, simply by changing the duration of a heating step. This method, termed ZOOM, isotropically expands samples up to eightfold in a single expansion process. ZOOM preserves biomolecules for post-processing labelings and supports multi-round expansion for the imaging of a single sample at multiple zoom factors. ZOOM can be flexibly and scalably applied to nanoscale imaging of diverse samples, ranging from cultured cells to thick tissues, as well as bacteria, exoskeletal Caenorhabditis elegans, and human brain samples.