Reinforcing Hydrogel by Nonsolvent-Quenching-Facilitated In Situ Nanofibrosis.

Nanofibrous hydrogels are pervasive in load-bearing soft tissues, which are believed to be key to their extraordinary mechanical properties. Enlighted by this phenomenon, a novel reinforcing strategy for polymeric hydrogels is proposed, where polymer segments in the hydrogels are induced to form nanofibers in situ by bolstering their controllable aggregation at the nanoscale level. Poly(vinyl alcohol) hydrogels are chosen to demonstrate the virtue of this strategy. A nonsolvent-quenching step is introduced into the conventional solvent-exchange hydrogel preparation approach, which readily promotes the formation of nanofibrous hydrogels in the following solvent-tempering process. The resultant nanofibrous hydrogels demonstrate significantly improved mechanical properties and swelling resistance, compared to the conventional solvent-exchange hydrogels with identical compositions. This work validates the hypothesis that bundling polymer chains to form nanofibers can lead to nanofibrous hydrogels with remarkably enhanced mechanical performances, which may open a new horizon for single-component hydrogel reinforcement.

Fabrication of moldable chitosan gels via thermally induced phase separation in aqueous alcohol solutions.

Wide application of chitosan in modern technologies is limited by the lack of reliable and low-cost techniques to prepare size-tuned constructs with a complex surface morphology, improved optical and mechanical properties. We report a new simple method for preparation of transparent thermoreversible chitosan alcogels from chitosan/H2O/ethanol ternary systems. This method, termed "low temperature thermally induced phase separation under non-freezing conditions" (LT-TIPS-NF), fine tunes gelation by adjusting only temperature (from 5 to -25 °C) and varying the initial content of chitosan (from 0.5 to 2.0 wt%) and ethanol (from 28.5 to 47.5 vol%). Transparent non-swelling final constructs of complex shape are prepared by fixing the pre-formed alcogels with a base solution. The size of the gel constructs is limited only by the dimensions of the mold and the cooling chamber. The LT-TIPS-NF is applicable both in injection molding and 3D printing techniques. The in vitro and in vivo experiments show the absence of prominent cytotoxicity and well-defined cell adhesion on the obtained hydrogels. Thus, this facile and scalable technique provides the multifunctional chitosan gel preparation with easily controlled properties exploiting inexpensive, renewable, and environmentally friendly source polysaccharide. These materials have prospects for a variety of uses, especially for biomedical applications.

Highly Adhesive, Stretchable and Breathable Gelatin Methacryloyl-based Nanofibrous Hydrogels for Wound Dressings.

Adhesive and stretchable nanofibrous hydrogels have attracted extensive attraction in wound dressings, especially for joint wound treatment. However, adhesive hydrogels tend to display poor stretchable behavior. It is still a significant challenge to integrate excellent adhesiveness and stretchability in a nanofibrous hydrogel. Herein, a highly adhesive, stretchable, and breathable nanofibrous hydrogel was developed via an in situ hybrid cross-linking strategy of electrospun nanofibers comprising dopamine (DA) and gelatin methacryloyl (GelMA). Benefiting from the balance of cohesion and adhesion based on photocross-linking of methacryloyl (MA) groups in GelMA and the chemical/physical reaction between GelMA and DA, the nanofibrous hydrogels exhibited tunable adhesive and mechanical properties through varying MA substitution degrees of GelMA. The optimized GelMA60-DA exhibited 2.0 times larger tensile strength (2.4 MPa) with an elongation of about 200%, 2.3 times greater adhesive strength (9.1 kPa) on porcine skin, and 3.1 times higher water vapor transmission rate (10.9 kg m-2 d-1) compared with gelatin nanofibrous hydrogels. In parallel, the GelMA60-DA nanofibrous hydrogels could facilitate cell growth and accelerate wound healing. This work presented a type of breathable nanofibrous hydrogels with excellent adhesive and stretchable capacities, showing great promise as wound dressings.

Stretchable, tough and elastic nanofibrous hydrogels with dermis-mimicking network structure.

Nanofiber-structured hydrogels with robust mechanical properties are promising candidates for the development of multifunctional materials in advanced fields. However, creating such materials that combine the virtues of high elongation, robust strength, and good elasticity remains an enormous challenge. Here, we demonstrate a nature-inspired methodology to fabricate dermis-mimicking network structured electrospun nanofibrous hydrogels with robust mechanical properties by combining the advantages of sustainable plant-based zein and elastic waterborne polyurethane (WPU). The reversible hydrogen bonding and strong covalent bonding between zein and WPU molecules are constructed in the double-network (DN) structured nanofibrous hydrogels (NFHs) with tunable stretchability and strength. The resulting NFHs exhibit the integrated characteristics of a stretch of 683%, a fracture strength of 6.5 MPa, a toughness of 20.7 MJ m-3, and complete recovery from large deformation. This nature-inspired structural design strategy may pave the way for designing mechanically robust nanofibrous hydrogels in structurally adaptive and scalable form.

Absorbable Thioether Grafted Hyaluronic Acid Nanofibrous Hydrogel for Synergistic Modulation of Inflammation Microenvironment to Accelerate Chronic Diabetic Wound Healing.

Current standard of care dressings are unsatisfactorily inefficacious for the treatment of chronic wounds. Chronic inflammation is the primary cause of the long-term incurable nature of chronic wounds. Herein, an absorbable nanofibrous hydrogel is developed for synergistic modulation of the inflammation microenvironment to accelerate chronic diabetic wound healing. The electrospun thioether grafted hyaluronic acid nanofibers (FHHA-S/Fe) are able to form a nanofibrous hydrogel in situ on the wound bed. This hydrogel degrades and is absorbed gradually within 3 days. The grafted thioethers on HHA can scavenge the reactive oxygen species quickly in the early inflammation phase to relieve the inflammation reactions. Additionally, the HHA itself is able to promote the transformation of the gathered M1 macrophages to the M2 phenotype, thus synergistically accelerating the wound healing phase transition from inflammation to proliferation and remodeling. On the chronic diabetic wound model, the average remaining wound area after FHHA-S/Fe treatment is much smaller than both that of FHHA/Fe without grafted thioethers and the control group, especially in the early wound healing stage. Therefore, this facile dressing strategy with intrinsic dual modulation mechanisms of the wound inflammation microenvironment may act as an effective and safe treatment strategy for chronic wound management.

Preparation of fibrin gel scaffolds containing MWCNT/PU nanofibers for neural tissue engineering.

Compared to the peripheral nervous system, in the central nervous system (CNS) disorders, neurons are less able to regenerate and reconstruct the neural tissue. Tissue engineering is considered as a promising approach for neural regeneration and restoring neurologic function after CNS injuries. Nanofibrous hydrogels have been recently used as three-dimensional (3D) scaffolds for tissue engineering applications. In this kind of composites, hydrogels are incorporated with fibers to enhance their poor mechanical properties. Furthermore, introducing meshes within hydrogels can result in composites associated with advantages of both components. In the present study, we have prepared 3D nanofibrous hydrogel scaffolds based on fibrin/polyurethane/multiwall carbon nanotube (fibrin/PU/MWCNT), for application as composite scaffolds for neural tissue engineering. The fabricated fibrin/PU/MWCNT hydrogel scaffolds were characterized and their ability to support cell attachment and viability was assessed in comparison with fibrin hydrogel. Scanning electron microscopy (SEM) analysis was performed to examine the microstructural features of scaffolds. The rate of biodegradation and rheological properties of scaffolds were also investigated. After isolation of human endometrial stem cells (hEnSCs), they were cultured into the scaffolds, then their attachment and viability were assessed through SEM analysis, MTT assay and DAPI staining. Based on the results, the viability and proliferation of hEnSCs in the fibrin/PU/MWCNT hydrogels were higher than those in fibrin hydrogels. Therefore, our novel fabricated fibrin/PU/MWCNT hydrogel is able to support cell proliferation and can be used as a scaffold to provide an appropriate microenvironment for enhancing cell viability. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 802-814, 2019.

Tunicate-mimetic nanofibrous hydrogel adhesive with improved wet adhesion.

The main impediment to medical application of biomaterial-based adhesives is their poor wet adhesion strength due to hydration-induced softening and dissolution. To solve this problem, we mimicked the wound healing process found in tunicates, which use a nanofiber structure and pyrogallol group to heal any damage on its tunic under sea water. We fabricated a tunicate-mimetic hydrogel adhesive based on a chitin nanofiber/gallic acid (a pyrogallol acid) composite. The pyrogallol group-mediated cross-linking and the nanofibrous structures improved the dissolution resistance and cohesion strength of the hydrogel compared to the amorphous polymeric hydrogels in wet condition. The tunicate-mimetic adhesives showed higher adhesion strength between fully hydrated skin tissues than did fibrin glue and mussel-mimetic adhesives. The tunicate mimetic hydrogels were produced at low cost from recyclable and abundant raw materials. This tunicate-mimetic adhesive system is an example of how natural materials can be engineered for biomedical applications.