Eggshell membrane-incorporated cell friendly tough hydrogels with ultra-adhesive property.

Adhesive and tough hydrogels have received increased attention for their potential biomedical applications. However, traditional hydrogels have limited utility in tissue engineering because they tend to exhibit low biocompatibility, low adhesiveness, and poor mechanical properties. Herein, the use of the eggshell membrane (ESM) for developing tough, cell-friendly, and ultra-adhesive hydrogels is described. The ESM enhances the performance of the hydrogel network in three ways. First, its covalent cross-linking with the polyacrylamide and alginate chains strengthens the hydrogel network. Second, it provides functional groups, such as amine and carboxyl moieties, which are well known for enhancing the surface adhesion of biomaterials, thereby increasing the adhesiveness of the hydrogel. Third, it is a bioactive agent and improves cell adhesion and proliferation on the constructed scaffold. In conclusion, this study proposes the unique design of ESM-incorporated hydrogels with high toughness, cell-friendly, and ultra-adhesive properties for various biomedical engineering applications.

One-step surface modification strategy with composition-tunable microgels: From bactericidal surface to cell-friendly surface.

As modifiers for biomaterial surfaces, soft colloidal particles not only have good film-forming properties, but can also contribute to the function of the biomaterial via their chemical and biological properties. This general approach has proven effective for surface modification, but little is known about methods to control the properties of the colloidal particles to regulate film formation and biological function. In this work, we prepared poly (N-isopropylacrylamide) microgels (ZQP) containing both a zwitterionic component (Z) to provide anti-fouling functionality, and a quaternary ammonium salt (Q) to give bactericidal functionality. Fine-tuning of the Z and Q contents allowed the preparation of microgels over a range of particle size, size distribution, charge, and film-forming capability. The films showed anti-adhesion and contact-killing properties versus Escherichia coli (E. Coli), depending on the chemical composition. They also showed excellent cytocompatibility relative to L929 cells. A variety of microgel-coated substrates (silicon wafer, PDMS, PU, PVC) showed long-term anti-bacterial activity and resistance to chemical and mechanical treatments. It is concluded that this approach allows the preparation of effective bactericidal, cytocompatible surfaces. The properties can be fine-tuned by regulation of the microgel composition, and the method is applicable universally, i.e., independent of substrate.

Soft Polymer-Based Technique for Cellular Force Sensing.

Soft polymers have emerged as a vital type of material adopted in biomedical engineering to perform various biomechanical characterisations such as sensing cellular forces. Distinct advantages of these materials used in cellular force sensing include maintaining normal functions of cells, resembling in vivo mechanical characteristics, and adapting to the customised functionality demanded in individual applications. A wide range of techniques has been developed with various designs and fabrication processes for the desired soft polymeric structures, as well as measurement methodologies in sensing cellular forces. This review highlights the merits and demerits of these soft polymer-based techniques for measuring cellular contraction force with emphasis on their quantitativeness and cell-friendliness. Moreover, how the viscoelastic properties of soft polymers influence the force measurement is addressed. More importantly, the future trends and advancements of soft polymer-based techniques, such as new designs and fabrication processes for cellular force sensing, are also addressed in this review.

Fabrication of 2D and 3D Cell Cluster Arrays Using a Cell-Friendly Photoresist.

Cells in 3D behave differently than cells in 2D. We develop a new method for the fabrication of 2D and 3D cell cluster arrays on an identical substrate using a cell-friendly photoresist, which enables comparative study between cells in 2D and 3D cell clusters. The fabricated cell cluster arrays maintain their structure up to 3 days with good viability. Using this method, 2D and 3D cancer cell clusters with comparable sizes are fabricated, and natural killer (NK) cell cytotoxicity assays are performed to assess how dimensionality of cancer cell clusters influence their susceptibility to immune cell-mediated killing.

Effects of Processing Parameters of 3D Bioprinting on the Cellular Activity of Bioinks.

In this review, few established cell printing techniques along with their parameters that affect the cell viability during bioprinting are considered. 3D bioprinting is developed on the principle of additive manufacturing using biomaterial inks and bioinks. Different bioprinting methods impose few challenges on cell printing such as shear stress, mechanical impact, heat, laser radiation, etc., which eventually lead to cell death. These factors also cause alteration of cells phenotype, recoverable or irrecoverable damages to the cells. Such challenges are not addressed in detail in the literature and scientific reports. Hence, this review presents a detailed discussion of several cellular bioprinting methods and their process-related impacts on cell viability, followed by probable mitigation techniques. Most of the printable bioinks encompass cells within hydrogel as scaffold material to avoid the direct exposure of the harsh printing environment on cells. However, the advantages of printing with scaffold-free cellular aggregates over cell-laden hydrogels have emerged very recently. Henceforth, optimal and favorable crosslinking mechanisms providing structural rigidity to the cell-laden printed constructs with ideal cell differentiation and proliferation, are discussed for improved understanding of cell printing methods for the future of organ printing and transplantation.

Nanosphere-based one-step strategy for efficient and nondestructive detection of circulating tumor cells.

Detecting viable circulating tumor cells (CTCs) without disruption to their functions for in vitro culture and functional study could unravel the biology of metastasis and promote the development of personalized anti-tumor therapies. However, existing CTC detection approaches commonly include CTC isolation and subsequent destructive identification, which damages CTC viability and functions and generates substantial CTC loss. To address the challenge of efficiently detecting viable CTCs for functional study, we develop a nanosphere-based cell-friendly one-step strategy. Immunonanospheres with prominent magnetic/fluorescence properties and extraordinary stability in complex matrices enable simultaneous efficient magnetic capture and specific fluorescence labeling of tumor cells directly in whole blood. The collected cells with fluorescent tags can be reliably identified, free of the tedious and destructive manipulations from conventional CTC identification. Hence, as few as 5 tumor cells in ca. 1mL of whole blood can be efficiently detected via only 20min incubation, and this strategy also shows good reproducibility with the relative standard deviation (RSD) of 8.7%. Moreover, due to the time-saving and gentle processing and the minimum disruption of immunonanospheres to cells, 93.8±0.1% of detected tumor cells retain cell viability and proliferation ability with negligible changes of cell functions, capacitating functional study on cell migration, invasion and glucose uptake. Additionally, this strategy exhibits successful CTC detection in 10/10 peripheral blood samples of cancer patients. Therefore, this nanosphere-based cell-friendly one-step strategy enables viable CTC detection and further functional analyses, which will help to unravel tumor metastasis and guide treatment selection.

Dynamic Micropatterning of Cells on Nanostructured Surfaces Using a Cell-friendly Photoresist.

Cellular dynamics under complex topographical microenvironments are important for many biological processes in development and diseases, but systematic investigation has been limited due to the lack of technology. Herein, we developed a new dynamic cell patterning method based on a cell-friendly photoresist polymer that allows in situ control of cell dynamics on nanostructured surfaces. Using this method, we quantitatively compared the spreading dynamics of cells on nanostructured surfaces to those on flat surfaces. Furthermore, we investigated how cells behaved when they simultaneously encountered two topographically distinct surfaces during spreading. This method will allow many exciting opportunities in the fundamental study of cellular dynamics.