Cell-adhesive double network self-healing hydrogel capable of cell and drug encapsulation: New platform to construct biomimetic environment with bottom-up approach.

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.

Integration of a fiber-based cell culture and biosensing system for monitoring of multiple protein markers secreted from stem cells.

We propose a new platform that can integrate three-dimensional cell culture scaffold and a surface-enhanced Raman spectroscopy (SERS)-based biosensor by stacking them to form a multilayer system, which would allow monitoring of the protein markers secreted from cultured stem cells without periodic cell and/or media collection. The cell culture scaffold supported the proliferation and osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). The SERS capture substrate detected protein markers in combination with SERS tag made with Au-Ag alloy nanoboxes. Incorporating the different Raman reporters into the SERS tag allowed easy identification of target proteins for multiplex assays. The resultant SERS-based immunoassay could detect the pg/mL levels of protein markers without crosstalk and interference. When one ADSC culture scaffold and multiple SERS capture substrates were integrated and incubated in differentiation culture media, our system was sufficiently sensitive to monitor time-dependent secretion of three different osteogenic protein markers from ADSCs during their osteogenic differentiation. Since the sensor and cell culture scaffold can be manipulated independently, various cell and biomarker combinations are possible to obtain relevant information regarding the actual state of the different types of cells.