In order to manipulate the complex behavior of cells in a 3-dimensional (3D) environment, it is important to provide the microenvironment that can accurately portray the complexity of highly ...anisotropic tissue structures. However, it is technically challenging to generate a complex microenvironment using conventional biomaterials that are mostly isotropic with limited bioactivity. In this study, the gelatin-hyaluronic acid hydrogel incorporated with aqueous-dispersible, short nanofibers capable of in situ alignment is developed to emulate the native heterogeneous extracellular matrix consisting of fibrous and non-fibrous components. The gelatin nanofibers containing magnetic nanoparticles, which could be aligned by external magnetic field, are dispersed and embedded in gelatin-hyaluronic acid hydrogel encapsulated with dermal fibroblasts. The aligned nanofibers via magnetic field could be safely integrated into the hydrogel, and the process could be repeated to generate larger 3D hydrogels with variable nanofiber alignments. The aligned nanofibers in the hydrogel can more effectively guide the anisotropic morphology (e.g., elongation) of dermal fibroblasts than random nanofibers, whereas myofibroblastic differentiation is more prominent in random nanofibers. At a given nanofiber configuration, the hydrogel composition having intermediate hyaluronic acid content induces myofibroblastic differentiation. These results indicate that modulating the degree of nanofiber alignment and the hyaluronic acid content of the hydrogel are crucial factors that critically influence the fibroblast phenotypes. The nanofiber-composite hydrogel capable of directional nanofiber alignment and tunable material composition can effectively induce a wide array of phenotypic plasticity in 3D cell culture.
•Multifunctional alginate is created via two different reaction pathways.•Cell adhesion molecules (CAM) is linked to carboxylic groups via amide coupling.•Methacrylate is conjugated to hydroxyl ...groups via nucleophilic addition.•CAM-methacrylic alginate is used as a crosslinker to develop hydrogels.•Mechanical and cell adhesive properties of hydrogels are controlled independently.
Alginate is an abundant natural polysaccharide widely utilized in various biomedical applications. Alginate also possesses numerous hydroxyl and carboxylate functional groups that allow chemical modifications to introduce different functionalities. However, it is difficult to apply various chemical reactions to alginate due to limited solubility in organic solvents. Herein, functional moieties for radical polymerization and cell adhesion were separately conjugated to hydroxyl and carboxylate groups of alginate, respectively, in order to independently control the crosslinking density and cell adhesive properties of hydrogels. Sodium counterions of alginate are first substituted with tetrabutylammonium ions to facilitate the dissolution in an organic solvent, followed by in situ conjugations of (1) cell adhesion molecules (CAM) via carbodiimide-mediated amide formation and (2) methacrylate via ring-opening nucleophilic reaction. The resulting CAM-linked methacrylic alginate was able to not only crosslink different monomers to form hydrogels with varying mechanical properties, but also induce stable cell adhesion to the hydrogels.
Hydrogels and nanofibers have been firmly established as go‐to materials for various biomedical applications. They have been mostly utilized separately, rarely together, because of their distinctive ...attributes and shortcomings. However, the potential benefits of integrating nanofibers with hydrogels to synergistically combine their functionalities while attenuating their drawbacks are increasingly recognized. Compared to other nanocomposite materials, incorporating nanofibers into hydrogel has the distinct advantage of emulating the hierarchical structure of natural extracellular environment needed for cell and tissue culture. The most important technological aspect of developing “nanofiber‐composite hydrogel” is generating nanofibers made of various polymers that are cross‐linked and short enough to maintain stable dispersion in hydrated environment. In this review, recent research efforts to develop nanofiber‐composite hydrogels are presented, with added emphasis on nanofiber processing techniques. Several notable examples of implementing nanofiber‐composite hydrogels for biomedical applications are also introduced.
In order to portray heterogeneous and hierarchical 3D tissue microenvironment more accurately in addition to enhancing the physicomechanical properties, there is a concerted research effort geared toward integrating nanofibers and hydrogels. In this review, recent technological advances in nanofiber‐composite hydrogels are introduced, with special emphasis on nanofiber processing that allows stable dispersion and integration in hydrogels.
Fibrosis is one of the most frequent occurrences during one's lifetime, identified by various physiological changes including, most notably, excessive deposition of extracellular matrix (ECM). ...Despite its physiological importance, it is still a significant challenge to conduct a systematic investigation of tissue fibrosis, mainly due to the lack of in vitro 3D tissue model that can accurately portray the characteristic features of fibrotic events. Herein, a hybrid hydrogel system incorporating dispersible nanofibers is developed to emulate highly collagenous deposits formed within a fibrotic tissue leading to altered mechanotopographical properties. Micrometer‐length, aqueous‐stable nanofibers consisting of crosslinked gelatin network embedded with graphene oxide (GO) or reduced graphene (rGO) are infused into hydrogel, resulting in controllable mechanotopographical properties while maintaining permeability sufficiently enough for various cellular activities. Ultimately, the ability to induce fibrotic behavior of fibroblasts cultured in these mechanotopography‐controlled, nanofiber‐laden hydrogels is investigated in detail.
A 3D cell culture platform emulating fibrotic tissue microenvironment is developed by incorporating micrometer‐length nanofibers with controllable mechanotopography into hydrogels. This “localized” crosslinking with nanofibers allows the control of mechanotopographical properties of hydrogels to promote myofibroblast differentiation via enhanced mechanosensing while maintaining spatial availability to induce sufficient cellular activities, overcoming the limitation of conventional hydrogel system with limited permeability.
Multiscale polymer engineering, involving chemical modification to control their triboelectric polarities as well as physicomechanical modification to maximize charge transfer and structural ...durability, is paramount to developing a high‐performance triboelectric nanogenerator (TENG). This report introduces a highly efficient and comprehensive strategy to engineer high‐performance TENG based on multifunctional polysuccinimide (PSI). With the ability of PSI to undergo facile nucleophilic addition with amines, sodium sulfate and quaternary ammonium chlorides having opposite charged groups are conjugated to PSI in varying densities. The resulting Sulfo‐PSI and TMAC‐PSI, respectively, processed into nanofibrous films, demonstrate highly enhanced and variable triboelectric properties based on the charge type and density. To further enhance the mechanical toughness and biocompatibility necessary for wearable applications, these PSI nanofibers are processed into alginate aerogel (AG). The sustained triboelectric performance of this nanofiber‐AG TENG as a wearable energy harvester and biosensor is examined and validated in detail.
A nanofiber‐infused aerogel is developed as a new material platform for triboelectric nanogenerators. Functional polysuccinimide‐based nanofibers with tunable triboelectric polarity and mechanically conformal and durable aerogel are synergistically combined for optimal triboelectric performance and wearability.
Culturing autologous cells with therapeutic potential derived from a patient within a bioactive scaffold to induce functioning tissue formation is considered the ideal methodology towards realizing ...patient-specific regenerative medicine. Hydrogels are often employed as the scaffold material for this purpose mainly for their tunable mechanical and diffusional properties as well as presenting cell-responsive moieties. Herein, a two-fold strategy was employed to control the physicomechanical properties and microarchitecture of hydrogels to maximize the efficacy of engineered hepatic tissues. First, a hydrophilic polymeric crosslinker with a tunable degree of reactive functional groups was employed to control the mechanical properties in a wide range while minimizing the change in diffusional properties. Second, photolithography technique was utilized to introduce microchannels into hydrogels to overcome the critical diffusional limit of bulk hydrogels. Encapsulating hepatic progenitor cells derived via direct reprogramming of tissue-harvested fibroblasts, the application of this strategy to control the mechanics, diffusion, and architecture of hydrogels in a combinatorial manner could allow the optimization of their hepatic functions. The regenerative capacity of this engineered hepatic tissue was further demonstrated using an in vivo acute liver injury model.
Magnetoelectric Paper
In article number 2311154 by Myoung Hoon Song, Chaenyung Cha, Jiyun Kim, and co‐workers, a flexible, biodegradable, and wireless bioelectronic paper is developed showing ...significant scalability, design flexibility, and rapid customizability through simple paper crafting techniques such as origami and kirigami.
Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost‐effective ...personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead‐free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high‐selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron‐like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.
A flexible, biodegradable bioelectronic paper featuring homogeneously distributed wireless stimulation functionality is presented. This paper synergistically combines lead‐free magnetoelectric nanoparticles for external magnetic field‐induced electrical stimulation and flexible, biodegradable nanofibers for high‐selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. Scalability, design flexibility, and rapid customizability are demonstrated through simple paper crafting techniques such as origami and kirigami.
Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. ...Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.
This study introduces a practical approach utilizing microfluidic trap and mixer modules fabricated with polydimethylsiloxane (PDMS) microfluidic devices. These modules were employed to capture and ...fluorescently label various randomly shaped microplastics (MPs) like polyethylene (PE), polypropylene (PP), and polystyrene (PS). Within the MPs trap module, grooves were incorporated into a straight-lined channel using SU-8 photolithography. This design induced turbulence effectively trapping and gathering the MPs within aqueous phases at 15 groove spaces, which achieved a trapping efficiency of up to 69% for PS MPs sized at a flow rate of 2 mL/min. Additionally, a mixer module featuring two flow inlets was designed to create a serpentine microfluidic channel, whose design significantly reduced sample and reagent (Nile Red) consumption during MP fluorescence staining at 80 °C. Furthermore, 2 nm gold nanoparticles (Au NPs), conjugated with a PS binding peptide (PSBP), were examined as an alternative fluorescent agent at room temperature. Photoluminescence (PL) and Fourier transform infrared (FT-IR) showcased efficiency of mixer module in labeling 30 mL MP solutions within a short time of 15 min. Moreover, a combined platform integrating trap and mixer devices was devised, incorporating a disposable heating pad and filter paper unit, which offers a simplified and compact MPs staining tool including spherical PE nanoplastics (200 nm–99 μm). This study aims to propose a preliminary concept for a lab-on-a-chip, facilitating the simultaneous collection and fluorescent labeling, which can be instrumentally implemented in future MPs monitoring.
