Injectable Hydrogels Based on Hyaluronic Acid and Gelatin Combined with Salvianolic Acid B and Vascular Endothelial Growth Factor for Treatment of Traumatic Brain Injury in Mice.

Traumatic brain injury (TBI) leads to structural damage in the brain, and is one of the major causes of disability and death in the world. Herein, we developed a composite injectable hydrogel (HA/Gel) composed of hyaluronic acid (HA) and gelatin (Gel), loaded with vascular endothelial growth factor (VEGF) and salvianolic acid B (SAB) for treatment of TBI. The HA/Gel hydrogels were formed by the coupling of phenol-rich tyramine-modified HA (HA-TA) and tyramine-modified Gel (Gel-TA) catalyzed by horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). SEM results showed that HA/Gel hydrogel had a porous structure. Rheological test results showed that the hydrogel possessed appropriate rheological properties, and UV spectrophotometry results showed that the hydrogel exhibited excellent SAB release performance. The results of LIVE/DEAD staining, CCK-8 and Phalloidin/DAPI fluorescence staining showed that the HA/Gel hydrogel possessed good cell biocompatibility. Moreover, the hydrogels loaded with SAB and VEGF (HA/Gel/SAB/VEGF) could effectively promote the proliferation of bone marrow mesenchymal stem cells (BMSCs). In addition, the results of H&E staining, CD31 and α-SMA immunofluorescence staining showed that the HA/Gel/SAB/VEGF hydrogel possessed good in vivo biocompatibility and pro-angiogenic ability. Furthermore, immunohistochemical results showed that the injection of HA/Gel/SAB/VEGF hydrogel to the injury site could effectively reduce the volume of defective tissues in traumatic brain injured mice. Our results suggest that the injection of HA/Gel hydrogel loaded with SAB and VEGF might provide a new approach for therapeutic brain tissue repair after traumatic brain injury.

Fabrication of antibacterial poly (L-lactic acid)/tea polyphenol blend films via reactive blending using SG copolymer.

Poly (L-lactic acid) (PLLA) composite materials with both excellent antibacterial properties and mechanical properties are highly desirable for both food packaging and biomedical applications. However, a facile method to prepare transparent PLLA composite films with both excellent antibacterial and mechanical properties is still lacking. In this work, blend films based on PLLA, tea polyphenols (TP) and poly (styrene-co-glycidyl methacrylate) (SG) copolymers (PLLA/TP/SG) were prepared by melt blending using twin screw extruder. The blend films showed high transparency with a brownish color originated from tea polyphenols. Both SEM and DSC analyses confirmed that the blends are thermodynamically compatible. GPC and mechanical assessments demonstrated that the PLLA/TP binary blends exhibit reduced molecular weight and compromised mechanical properties, compared to neat PLLA. However, incorporating SG copolymer resulted in increased molecular weight and improved mechanical properties for the PLLA/TP/SG blends. The FT-IR spectra exhibited a shift to lower wavenumber for the absorption peak associated with the benzene ring on TPs after blending with PLLA and SG, indicating the occurrence of transesterification between PLLA and TP. Plate coating studies revealed that the PLLA/TP/SG blends with TP incorporation at 5 wt% exhibited a bacteriostatic rate of 99.99 % against Staphylococcus aureus and Escherichia coli. Overall, our study reveals that the PLLA/TP/SG blend films exhibit excellent antibacterial properties coupled with good mechanical properties, rendering them a promising candidate for antibacterial packaging materials.

Salvianolic-Acid-B-Loaded HA Self-Healing Hydrogel Promotes Diabetic Wound Healing through Promotion of Anti-Inflammation and Angiogenesis.

Inflammatory dysfunction and angiogenesis inhibition are two main factors leading to the delayed healing of diabetic wounds. Hydrogels with anti-inflammatory and angiogenesis-promoting effects have been considered as promising wound care materials. Herein, a salvianolic acid B (SAB)-loaded hyaluronic acid (HA) self-healing hydrogel (HA/SAB) with anti-inflammatory and pro-angiogenesis capacities for diabetic wound healing is reported. The HA hydrogel was prepared via the covalent cross-linking of aldehyde groups in oxidized HA (OHA) and hydrazide groups in adipic dihydrazide (ADH)-modified HA (HA-ADH) with the formation of reversible acylhydrazone bonds. The obtained HA hydrogel exhibited multiple favorable properties such as porous structures, excellent self-healing properties, a sustainable release capacity of SAB, as well as excellent cytocompatibility. In addition, the effects of the SAB-loaded HA self-healing hydrogel were investigated via a full-thickness skin defect model using diabetic rats. The HA/SAB hydrogel showed enhanced skin regeneration effects with accelerated wound closure, shorter remaining dermal space length, thicker granulation tissue formation, and more collagen deposition. Furthermore, reduced inflammatory response and enhanced vascularization were found with HA/SAB2.5 hydrogel-treated wounds, indicating that the hydrogel promotes diabetic wound healing through the promotion of anti-inflammation and angiogenesis. Our results suggest that the fabricated SAB-loaded HA self-healing hydrogel is promising as a wound dressing for the treatment of diabetic wounds.

Percolation Network Formation in Nylon 6/Montmorillonite Nanocomposites: A Critical Structural Insight and the Impact on Solidification Process and Mechanical Behavior.

The incorporation of montmorillonite (MMT) into Nylon 6 can endow advantages like improved mechanical strength and thermal stability, making Nylon 6/MMT a possible ideal alternative for Nylon 66. However, the relationship between the microstructure and physical properties of nylon 6/MMT nanocomposites is unclear so far due to the complicated system, including the highly asymmetric geometry of the exfoliated MMT layer and the complicated interaction between MMT layers and entangled nylon 6 chains. Herein, we focus on two processes, namely the impact of MMT on the solidification procedure during molding and the toughness-brittleness transition during the tensile stretch, in order to elucidate the structure-property relationship of nylon 6/MMT composites. We firstly studied the solidification process of nylon 6/MMT with bending height experiments. The results showed that the solidification process occurs prior to the crystallization of nylon 6, indicating that a physical crosslinked network rather than a crystalline structure is the reason for the solidification process. Furthermore, the solidification speed has a step change at around 2 wt% MMT content, indicating that the MMT percolation network is related to the transition. We further studied the influence of MMT inclusion on the mechanical properties, and found the tensile strain at break showed a similar step change at around 2 wt% MMT content, which further confirms the existence of an MMT percolation network above 2 wt% MMT content. It was generally believed that the main effect of MMT on nylon 6 is the nanofiller enforcement; we found that the percolation effect of the highly asymmetric 2-D nanofiller plays a central role in influencing the mechanical properties and solidification behavior during molding.

Opposing Phase-Segregation and Hydrogen-Bonding Forces in Supramolecular Polymers.

Phase segregation between different macromolecules and specific weak interactions are the basis of molecular organization in many biological systems, which are held together by attractive hydrogen bonds (H-bonds) and dissociated by phase segregation. We report significant changes in the association behavior of covalent H-bonds by the phase of attached polymer chains. Depending on the aggregation state, we observed either intact H-bonds despite segregation of the phases, or macrophase separation with a larger amount of H-bonding dissociation.

Unveiling the molecular mechanism of self-healing in a telechelic, supramolecular polymer network.

Reversible polymeric networks can show self-healing properties due to their ability to reassemble after application of stress and fracture, but typically the relation between equilibrium molecular dynamics and self-healing kinetics has been difficult to disentangle. Here we present a well-characterized, self-assembled bulk network based on supramolecular assemblies, that allows a clear distinction between chain dynamics and network relaxation. Small angle x-ray scattering and rheological measurements provide evidence for a structurally well-defined, dense network of interconnected aggregates giving mechanical strength to the material. Different from a covalent network, the dynamic character of the supramolecular bonds enables macroscopic flow on a longer time scale and the establishment of an equilibrium structure. A combination of linear and nonlinear rheological measurements clearly identifies the terminal relaxation process as being responsible for the process of self-healing.