Photocrosslinkable materials have been frequently used for constructing soft and biomimetic hydrogels for tissue engineering. Although ultraviolet (UV) light is commonly used for photocrosslinking such materials, its use has been associated with several biosafety concerns such as DNA damage, accelerated aging of tissues, and cancer. Here we report an injectable visible light crosslinked gelatin-based hydrogel for myocardium regeneration. Mechanical characterization revealed that the compressive moduli of the engineered hydrogels could be tuned in the range of 5–56 kPa by changing the concentrations of the initiator, co-initiator and co-monomer in the precursor formulation. In addition, the average pore sizes (26–103 μm) and swelling ratios (7–13%) were also shown to be tunable by varying the hydrogel formulation. In vitro studies showed that visible light crosslinked GelMA hydrogels supported the growth and function of primary cardiomyocytes (CMs). In addition, the engineered materials were shown to be biocompatible in vivo, and could be successfully delivered to the heart after myocardial infarction in an animal model to promote tissue healing. The developed visible light crosslinked hydrogel could be used for the repair of various soft tissues such as the myocardium and for the treatment of cardiovascular diseases with enhanced therapeutic functionality.
Pancreatic ductal adenocarcinoma (PDAC) is usually detected late in the disease process. Clinical workup through imaging and tissue biopsies is often complex and expensive due to a paucity of reliable biomarkers. We used an advanced multiplexed plasmonic assay to analyze circulating tumor-derived extracellular vesicles (tEVs) in more than 100 clinical populations. Using EV-based protein marker profiling, we identified a signature of five markers (PDACEV signature) for PDAC detection. In our prospective cohort, the accuracy for the PDACEV signature was 84% [95% confidence interval (CI), 69 to 93%] but only 63 to 72% for single-marker screening. One of the best markers, GPC1 alone, had a sensitivity of 82% (CI, 60 to 95%) and a specificity of 52% (CI, 30 to 74%), whereas the PDACEV signature showed a sensitivity of 86% (CI, 65 to 97%) and a specificity of 81% (CI, 58 to 95%). The PDACEV signature of tEVs offered higher sensitivity, specificity, and accuracy than the existing serum marker (CA 19-9) or single–tEV marker analyses. This approach should improve the diagnosis of pancreatic cancer.
Background: Melanins are a group of biopigments in microorganisms that generate a wide range of colorants. Due to their multifunctionality, including ultraviolet protection, radical scavenging, and photothermal conversion, in addition to their intrinsic biocompatibility, natural melanins and synthetic melanin-like nanomaterials have been suggested as novel nano-bio platforms in biomedical applications. Main body: Recent approaches in the synthesis of melanin-like nanomaterials and their biomedical applications have briefly been reviewed. Melanin-like nanomaterials have been suggested as endogenous chromophores for photoacoustic imaging and radical scavengers for the treatment of inflammatory diseases. The photothermal conversion ability of these materials under near-infrared irradiation allows hyperthermia-mediated cancer treatments, and their intrinsic fluorescence can be an indicator in biosensing applications. Furthermore, catechol-rich melanin and melanin-like nanomaterials possess a versatile affinity for various functional organic and inorganic additives, allowing the design of multifunctional hybrid nanomaterials that expand their range of applications in bioimaging, therapy, theranostics, and biosensing. Conclusion: Melanin-like natural and synthetic nanomaterials have emerged; however, the under-elucidated chemical structures of these materials are still a major obstacle to the construction of novel nanomaterials through bottom-up approaches and tuning the material properties at the molecular level. Further advancements in melanin-based medical applications can be achieved with the incorporation of next-generation chemical and molecular analytical tools.