A Multifunctional, Tough, Stretchable, and Transparent Curcumin Hydrogel with Potent Antimicrobial, Antioxidative, Anti-inflammatory, and Angiogenesis Capabilities for Diabetic Wound Healing.

The treatment of diabetic chronic wounds is still faced with great challenges, mainly due to wound infection, excessive inflammation, and peripheral vascular disease in the wound area. Therefore, it is of great importance to develop a novel multifunctional hydrogel with high efficiency to accelerate diabetic wound healing. Curcumin (Cur), a Chinese herbal, has shown great potential in enhancing the healing of diabetic chronic wounds because of its immunomodulatory and pro-angiogenic properties. However, its low aqueous solubility, poor bioavailability, and chemical instability have limited its clinical applications. To address these current bottlenecks, novel poly(vinyl alcohol) (PVA)-chitosan (CS)/sodium alginate (SA)-Cur (PCSA) hydrogels were prepared for the first time, and they demonstrated all of the above intriguing performances by the Michael addition reaction of CS and Cur. PCSA hydrogels show multiple dynamic bonds, which possess strong mechanical properties (tensile stress: ∼0.980 MPa; toughness: ∼258.45 kJ/m3; and compressive strength: ∼7.38 MPa at strain of 80%). These intriguing performances provided an optimal microenvironment for cell migration and proliferation and also promoted the growth of blood vessels, leading to early angiogenesis. Importantly, the experimental results demonstrated that PCSA hydrogels can effectively transform pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages without the need for additional ingredients in vitro. Benefiting from these characteristics, a full-thickness diabetic wound in a rat model demonstrated that PCSA hydrogels can effectively accelerate wound healing via ROS-scavenging, downregulation of IL-1ß, and upregulation of CD31 expression, resulting in angiogenesis and collagen deposition. This strategy not only provides a simple and safe Cur-based hydrogel for diabetic wound healing but also highlights the significant potential for the development of high-performance biomaterials for promoting diabetic wound healing using traditional Chinese medicine.

Rab37 Promotes Endothelial Differentiation and Accelerates ADSC-Mediated Diabetic Wound Healing through Regulating Secretion of Hsp90α and TIMP1.

Accumulating evidence indicates that adipose tissue-derived mesenchymal stem cells (ADSCs) are an effective treatment for diabetic refractory wounds. However, the application of ADSCs to diabetic wounds is still limited, indicating that we still lack sufficient knowledge regarding regulators/mediators of ADSCs during wound healing. Rab37, a member of RabGTPase, may function as regulator of vesicle trafficking, which is a crucial event for the secretion of cytokines by ADSCs. Our previous study indicated that Rab37 promotes the adiopogenic differentiation of ADSCs. In this study, we explored the role of Rab37 in ADSC-mediated diabetic wound healing. An in vivo study in db/db diabetic mice showed that Rab37-expressing ADSCs shortened the wound closure time, improved re-epithelialization and collagen deposition, and promoted angiogenesis during wound healing. An in vitro study showed that Rab37 promoted the proliferation, migration and endothelial differentiation of ADSCs. LC-MS/MS analysis identified Hsp90α and TIMP1 as up-regulated cytokines in conditioned media of Rab37-ADSCs. The up-regulation of Rab37 enhanced the secretion of Hsp90α and TIMP1 during endothelial differentiation and under high-glucose exposure. Interestingly, Rab37 promoted the expression of TIMP1, but not Hsp90α, during endothelial differentiation. PLA showed that Rab37 can directly bind to Hsp90α orTIMP1 in ADSCs. Moreover, Hsp90α and TIMP1 knockdown compromised the promoting effects of Rab37 on the proliferation, migration and endothelial differentiation of ADSCs. In conclusion, Rab37 promotes the proliferation, migration and endothelial differentiation of ADSCs and accelerates ADSC-mediated diabetic wound healing through regulating the secretion of Hsp90α and TIMP1.

Mussel foot protein inspired tough tissue-selective underwater adhesive hydrogel.

Mussel foot proteins (Mfps) show strong adhesion to underwater substrates, making mussels tightly cling to reefs to withstand the sea current. Therefore, Mfps-inspired tissue adhesives have aroused much research interest, but tough underwater biological tissue adhesion is still a great challenge. Herein, we report a tough and reversible wet tissue-selective adhesive hydrogel made of poly(acrylic acid-co-catechol) and chitosan (CS). It provides negatively charged -COO-, positively charged -NH3+, catechol group and hydrophobic alkyl chain, resemble amino acids, catechol and hydrophobic units in Mfps. Due to the covalent/electrostatic attraction/π-π/cationic-π/hydrogen bonding, in addition to the hydrophobic interaction from the long hydrophobic alkyl chain of the catechol derivative, the hydrogel has a high cohesion strength and toughness, i.e., tensile stress, fracture strain and fracture toughness of ∼0.57 MPa, 2510% and 6620 J m-2, respectively. As a tissue adhesive, its adhesion bonding to the porcine skin surface is so strong that its adhesion strength is almost equal to the tearing strength of the hydrogel. The 180-degree peeling adhesion energy of the hydrogel to blood-wetted porcine skin is notably ∼1010 J m-2. It can tightly and seamlessly adhere to the porcine small intestine, and has a bursting pressure of up to 520 mmHg. The hydrogel can be handily debonded from the porcine skin surface in the presence of aqueous solution at pH 8.0, and its adhesiveness is reversible for at least 20 cycles. It is supposed that the synergistic interactions of the adhesive catechol group, displacement of water on the wet skin surface by the positively charged -NH3+ groups of CS and the water-repelling potential of the hydrophobic unit of the catechol derivative, the protection of the catechol group from oxidation into a less adhesive quinone group, and the energy dissipation capacity of the mechanically tough hydrogel contribute to the strong and repeatable wet tissue adhesion.

An Antifreezing/Antiheating Hydrogel Containing Catechol Derivative Urushiol for Strong Wet Adhesion to Various Substrates.

Tough adhesive hydrogels that can tightly bond to wet tissue/polymer/ceramic/metal surfaces have great potentials in various fields. However, conventional adhesive hydrogels usually show short-term and nonreversible adhesion ability, as the water component in a hydrogel readily transforms to vapor or ice in response to fluctuation of environment temperature, hindering their applications in extreme conditions such as in freezing Arctic and roasting Africa. For the first time, urushiol (UH), a natural catechol derivative with a long alkyl side chain, is used as a starting material to copolymerize with acrylamide for fabricating adhesive hydrogels, which contain hydrophobic/hydrophilic moieties, antifreezing agent, and adhesive catechol groups. The antifreezer/moisturizer glycerol/water binary solvent dispersed in the hydrogel endows it with antifreezing/antiheating property. The hydrophobic association and π-π interaction from UH moieties of the copolymer greatly improve its mechanical strength (tensile stress: ∼0.12 MPa with strain of ∼1100%, toughness: ∼72 kJ/m3, compression stress: ∼6.72 MPa at strain of 90%). The hydrogel can strongly adhere to various dry/wet biological/polymeric/ceramic/metallic substrates at temperatures ranging from -45 to 50 °C. Under ambient conditions, its adhesion force to porcine skin, glass, and tinplate may reach up to 160, 425, and 275 N/m, respectively. Even stored at -45 or 50 °C for 30 d, the hydrogel still maintains good flexibility and robust adhesion force. It also shows repeatable underwater adhesion to biological tissue, glass, ceramic, plastic, and rubber. This novel antifreezing/antiheating adhesive hydrogel may be applied in extremely cold or hot environments and in underwater conditions.

Tough polyacrylamide-tannic acid-kaolin adhesive hydrogels for quick hemostatic application.

Adhesive hydrogels for wet and dynamic tissues are important for biomedical applications in order to withstand cyclic loading such as in the case of hemorrhaging control on the curved skins and heart tissues. However, the fabrication of hydrogels with strong mechanical properties, high adhesion strength, and hemostatic efficiency remains a big challenge. Inspired by the great adhesive behavior of mussels and Arion subfuscus, novel adhesive and hemostatic polyacrylamide-tannic acid-kaolin (PAAm-TA-KA) hydrogels were reported in this work. The hydrogels displayed high strength and toughness due to their physical and chemical crosslinking structures. The abundant catechol groups on tannic acid endow the hydrogels with strong and durable adhesion strength of up to 500 kPa on porcine skin. When applied onto human skin, the hydrogels could be easily peeled off without leaving any remains and causing any damages. The kaolin nanoparticles incorporated in the PAAm-TA-KA hydrogels not only served as a physical crosslinking agent, but an activator of the blood clotting factor FXII for accelerating the formation of thrombus. The strong tissue adhesion and blood coagulant potential of the PAAm-TA-KA hydrogels imparted them high hemostatic efficiency. The free-standing, adhesive, tough, cytocompatible, and hemostatic hydrogels are highly promising for traumatic bleeding control materials.

One-step recovery of noble metal ions from oil/water emulsions by chitin nanofibrous membrane for further recycling utilization.

A multifunctional membrane, prepared by filtration of partial deacetylated chitin nanofibers, was reported to realize one-step green recovery of noble metal ions from surfactant-stabilized oil/water emulsions. The chitin nanofibrous membrane (CNFM) has nanoporous structure with superhydrophilic and underwater superoleophobic surface and could effectively separate oil/water emulsion. Combining with the chelation ability/reduction of amino groups of chitin, CNFM could simultaneously extract noble metal ions from oily wastewater. Furthermore, the noble metal ions adsorbed on the CNFM could be in situ reduced into metal nanoparticles (NPs) by amino groups on chitin without adding extra reducing agents, to yield NPs-loaded CNFM. Surprisingly, the recovered NPs-loaded CNFM maintained excellent catalytic activities and even displayed peroxidase mimic behavior, showing high potentials in biosensing, green catalysis and related fields. Hence, this work provides a simple and sustainable way to realize directly recovery of noble metal ions from oil/water emulsion.