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Traditional bulk hydrogels containing antibiotics or metal ions often fall short in effectively treating wound infections due to mechanical limitations, bacterial resistance, and potential cytotoxicity. To address these challenges, an extracellular matrix (ECM)‐inspired antibacterial fibrous hydrogel featuring an anisotropic topological structure is developed that closely mimics the natural ECM environment. A novel antibacterial agent, PHMB‐VAN‐Gd (PVG), is synthesized by reacting polyhexamethylene biguanide (PHMB) with O‐Vanillin (VAN) to form the Schiff base ligand PHMB‐VAN (PV), followed by coordination with gadolinium ions (Gd3⁺). Employing silk fibroin (SF) as the matrix, the PVG complex is incorporated into fibrous hydrogels through electrospinning, generating structures that replicate the fibrous architecture of the ECM. The resulting SF‐PVG fibrous hydrogels exhibited robust antibacterial activity, effectively inhibiting bacterial growth and biofilm formation. Furthermore, the aligned fiber orientation and substantial mechanical strength of these hydrogels facilitated cellular functions, promoting cell attachment and proliferation. This study underscores the significant potential of SF‐PVG hydrogels for wound infection treatment. [ABSTRACT FROM AUTHOR]

Control over the organization of cells at the microscale level within supporting biomaterials can push forward the construction of complex tissue architectures for tissue engineering applications and enable fundamental studies of how tissue structure relates to its function. While cells patterning on 2D substrates is a relatively established and available procedure, micropatterning cells in biomimetic 3D hydrogels has been more challenging, especially with micro-scale resolution, and currently relies on sophisticated tools and protocols. We present a robust and accessible 'peel-off' method to micropattern large arrays of individual cells or cell-clusters of precise sizes in biological 3D hydrogels, such as fibrin and collagen gels, with control over cell-cell separation distance and neighboring cells position. We further demonstrate partial control over cell position in the z -dimension by stacking two layers in varying distances between the layers. To demonstrate the potential of the micropatterning gel platform, we study the matrix-mediated mechanical interaction between array of cells that are accurately separated in defined distances. A collective process of intense cell-generated densified bands emerging in the gel between near neighbors was identified, along which cells preferentially migrate, a process relevant to tissue morphogenesis. The presented 3D gel micropatterning method can be used to reveal fundamental morphogenetic processes, and to reconstruct any tissue geometry with micrometer resolution in 3D biomimetic gel environments, leveraging the engineering of tissues in complex architectures., (Creative Commons Attribution license.)

Diabetes wounds take longer to heal due to extended inflammation, decreased angiogenesis, bacterial infection, and oxidative stress. These factors underscore the need for biocompatible and multifunctional dressings with appropriate physicochemical and swelling properties to accelerate wound healing. Herein, insulin (Ins)-loaded, and silver (Ag) coated mesoporous polydopamine (mPD) nanoparticles were synthesized (Ag@Ins-mPD). The nanoparticles were dispersed into polycaprolactone/methacrylated hyaluronate aldehyde dispersion, electrospun to form nanofibers, and then photochemically crosslinked to form a fibrous hydrogel. The nanoparticle, fibrous hydrogel, and nanoparticle-reinforced fibrous hydrogel were characterized for their morphological, mechanical, physicochemical, swelling, drug-release, antibacterial, antioxidant, and cytocompatibility properties. The diabetic wound reconstruction potential of nanoparticle-reinforced fibrous hydrogel was studied using BALB/c mice. The results indicated that Ins-mPD acted as a reductant to synthesize Ag nanoparticles on their surface, held antibacterial and antioxidant potential, and their mesoporous properties are crucial for insulin loading and sustained release. The nanoparticle-reinforced scaffolds were uniform in architecture, porous, mechanically stable, showed good swelling, and possessed superior antibacterial, and cell-responsive properties. Furthermore, the designed fibrous hydrogel scaffold demonstrated good angiogenic, anti-inflammatory, increased collagen deposition, and faster wound repair capabilities, therefore, it could be used as a potential candidate for diabetic wound treatment. [Display omitted] • Insulin-loaded and silver-coated mesoporous polydopamine nanoparticles were synthesized. • Methacrylated hyaluronate aldehyde-based nanofibers were photochemically crosslinked to fabricate fibrous hydrogel. • Nanoparticles-reinforced fibrous hydrogel demonstrated antibacterial, cytocompatibility, and ROS-scavenging properties. • Fibrous hydrogel modulated anti-inflammatory, angiogenesis, collagen deposition, and diabetic wound reconstruction. [ABSTRACT FROM AUTHOR]

Interpenetrating polymer networks (IPNs) have gained great attention for a number of biomedical applications due to their improved properties compared to individual components alone. In this study, we investigated the capacity of newly-developed naturally-derived IPNs as potential biomaterials for tissue engineering. These IPNs combine the biologic properties of a fibrous fibrin network polymerized at the nanoscale and the mechanical stability of polyethylene oxide (PEO). First, we assessed their cytotoxicity in vitro on L929 fibroblasts. We further evaluated their biocompatibility ex vivo with a chick embryo organotypic culture model. Subcutaneous implantations of the matrices were subsequently conducted on nude mice to investigate their biocompatibility in vivo. Our preliminary data highlighted that our biomaterials were non-cytotoxic (viability above 90%). The organotypic culture showed that the IPN matrices induced higher cell adhesion (across all the explanted organ tissues) and migration (skin, intestine) than the control groups, suggesting the advantages of using a biomimetic, yet mechanically-reinforced IPN-based matrix. We observed no major inflammatory response up to 12 weeks post implantation. All together, these data suggest that these fibrin-based IPNs are promising biomaterials for tissue engineering. [ABSTRACT FROM AUTHOR]

Microarrays are powerful experimental tools for high-throughput screening of cellular behavior in multivariate microenvironments. Here, we present a new, facile and rapid screening method for probing cellular behavior in 3D tissue microenvironments. This method utilizes a photoclickable peptide microarray platform developed using electrospun fibrous poly(ethylene glycol) hydrogels and microarray contact printing. We investigated the utility of this platform with five different peptide motifs and ten cell types including stem, terminally differentiated, cancer or immune cells that were from either primary origin or cell lines and from different species. We validated the capabilities of this platform to screen arrays consisting of multiple peptide motifs and concentrations for selectivity to cellular adhesion and morphology. Moreover, this platform is amenable to controlled spatial presentation of peptides. We show that by leveraging the differential attachment affinities for two cell types to two different peptides, this platform can also be used to investigate cell-cell interactions through miniature co-culture peptide arrays. Our fibrous peptide microarray platform enables high-throughput screening of 3D tissue microenvironments in a facile and rapid manner to investigate cell-matrix interactions and cell-cell signaling and to identify optimal tissue microenvironments for cell-based therapies. [ABSTRACT FROM AUTHOR]

Use of organic templates for controlling the growth of inorganic crystals is one of the research topics in biomimetic field. In particular, oriented growth of hydroxyapatite (HAp) in organic fibrous matrix is provided a new view angle to study biomineralization of bone and its potential biomedical applications. The crystallization of HAp in fibrous hydrogels could mimic such biomineralization. In this paper, we report HAp nanorod crystal synthesized successfully by a biomimetic method using calcium chloride and ammonium dihydrogen phosphate as reagents in the presence of silk fibroin/sodium alginate (SF/SA) fibrous hydrogels. The effects of influence factors such as mineral times, pH, and temperature on controlling HAp nanorod crystals are discussed. The elongated HAp nanorods with rectangular column are grown with the increase of mineral times in biomimetic process. By changing pH, HAp nanorod crystals are obtained at alkaline condition in fibrous hydrogels. Moreover, compared to other temperatures, rod-shaped HAp crystals were formed at 20 °C. The results imply this to be an effective method for preparing HAp crystals with controllable morphology for bone repair application. [ABSTRACT FROM AUTHOR]

The biocompatible fibrous hydrogels were formed using physically cross-linked biopolymers. Gelation of silk fibroin (SF, from Bombyx mori silk) aqueous solution was effected by self-assembly and used to entrap blended sodium alginate (SA) without chemical cross-linking. SA was formed into SF/SA fibrous hydrogels with different mixing ratios, forming homogeneous nanofiber networks morphology. Measurements by XRD and FTIR indicated that silk I and silk II structure existed in the fibrous hydrogels and that the secondary structure of fibroin was transformed to β-sheet from random coil during this sol-gel transition process. The compressive stress of SF/SA fibrous hydrogels decreased slightly with increasing of SA content. At the same time, fibrous hydrogels degraded quickly after incubating in protease XIV solution than in PBS solution at 37 °C. For cultivating 12 days, human mesenchymal stem cells proliferated in SF/SA fibrous hydrogels. These fibrous hydrogels may be useful for biomedical applications due to biocompatibility and the widespread utility of hydrogel systems. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Soft tissue engineering has been seeking ways to mimic the natural extracellular microenvironment that allows cells to migrate and proliferate to regenerate new tissue. Therefore, the reconstruction of soft tissue requires a scaffold possessing the extracellular matrix (ECM)-mimicking fibrous structure and elastic property, which affect the cell functions and tissue regeneration. Herein, an effective method for fabricating nanofibrous hydrogel for soft tissue engineering is demonstrated using gelatin–hydroxyphenylpropionic acid (Gel–HPA) by electrospinning and enzymatic crosslinking. Gel–HPA fibrous hydrogel was prepared by crosslinking the electrospun fibers in ethanol-water solution with an optimized concentration of horseradish peroxidase (HRP) and H2O2. The prepared fibrous hydrogel held the soft and elastic mechanical property of hydrogels and the three-dimensional (3D) fibrous structure of electrospun fibers. It was proven that the hydrogel scaffolds were biocompatible, improving the cellular adhesion, spreading, and proliferation. Moreover, the fibrous hydrogel showed rapid biodegradability and promoted angiogenesis in vivo. Overall, this study represents a novel biomimetic approach to generate Gel–HPA fibrous hydrogel scaffolds which have excellent potential in soft tissue regeneration applications. [ABSTRACT FROM AUTHOR]

Abstract: In order to establish a novel artificial muscle model, an ionized fibrous hydrogel assembly (FHM) was prepared by means of surface-grafting acrylonitrile onto cellulose fiber and consequent hydrolysis. The structure and character of FHM was investigated. The FHM shows excellent chemomechanical character. This feature is closely interrelated to its molecular, morphological structure and texture. [Copyright &y& Elsevier]