Benedikt Gantert, Emine Karakaya, Florian Hofmann, Tomasz Jungst, Lorenz Meinel, Anja K Bosserhoff, Rainer Detsch, Tessa Lühmann
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引用次数: 0
Abstract
Biofabrication and three-dimensional (3D) bioprinting enable precise spatial arrangement of cells within biomaterial scaffolds. We developed an alginate-based and Förster resonance energy transfer (FRET)-responsive "turn-on" reporter ink platform to enable real-time monitoring of matrix metalloproteinase (MMP) activity. Three distinct MMP-cleavable turn-on peptide reporters were synthesized and characterized for their cell-specific cleavage profiles using recombinant MMPs, cell-derived media, and different cell cultures (NIH3T3, HEK293, and MelHo). All turn-on reporters were covalently and site-specifically incorporated into alginate dialdehyde (ADA) to yield an MMP reporter ink. The ADA reporter ink with an MMP 13 turn-on reporter was responsive to all tested cell types over time within the cast bulk constructs. The ADA reporter ink material blended with gelatin had comparable print resolution and structural fidelity as observed for ADA. The extrusion-based bioprinted MelHo cell grids, measuring 2 × 2 cm2 and containing 1 × 106 cells/mL, exhibited MMP activity responses comparable to those of the casted reporter ink system, with a 3-fold increase observed at 24 h. This study introduces a versatile, FRET-based alginate bioink platform for the real-time monitoring of MMP activities, expanding the toolkit to understand cellular performance in bioprinted 3D constructs.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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