An ECM-mimicking assembled gelatin/hyaluronic acid hydrogel with antibacterial and radical scavenging functions for accelerating open wound healing.

A multifunctional hydrogel dressing with hemostatic, antibacterial, and reactive oxygen species (ROS)-removing properties is highly desirable for the clinical treatment of open wounds. Although many wound dressings have been prepared, the modification of polymers is often involved in the preparation process, and the uncertainty of biological safety and stability of modified polymers hinders the clinical application of products. In this study, inspired by the composition and crosslinking pattern of extracellular matrix (ECM), a deeply ECM-mimicking multifunctional hydrogel dressing is created. Tannic acid (TA) and poly-ϵ-lysine (EPL) are added into a gelatin/hyaluronic acid (Gel/HA) matrix, and a stable hydrogel is formed due to the formation of the triple helix bundles of gelatin and hydrogen bonds between polymers. The introduction of TA and EPL endows the ECM-mimicking hydrogel with stable rheological properties, as well as antibacterial and hemostatic functions. The as-produced hydrogels have suitable swelling ratio, enzyme degradability, and good biocompatibility. In addition, it also shows a significant ability to eliminate ROS, which is confirmed by the elimination of 2,2-diphenyl-1-picrylhydrazyl free radical. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed ECM-mimicking Gel/HA hydrogels have a prominent effect on ECM formation and promotion of wound closure. Taken together, these findings suggest that the multifunctional hydrogels deeply mimicking the ECM are promising candidates for the clinical treatment of open wounds.

Polymorphic transient glycolipid assemblies with tunable lifespan and cargo release.

HYPOTHESIS: In living systems, dynamic processes like dissipative assembly, polymorph formation, and destabilization of hydrophobic domains play an indispensable role in the biochemical processes. Adaptation of biological self-assembly processes to an amphiphilic molecule leads to the fabrication of intelligent biomaterials with life-like behavior. EXPERIMENTS: An amphiphilic glycolipid molecule was engineered into various dissipative assemblies (vesicles and supramolecular nanotube-composed hydrogels) by using two activation steps, including heating-cooling and shear force in method-1 or boric acid/glycolipid complexation and shear force in method-2. The influence of number of activation steps on vesicle to nanotube phase transitions and activation method on the properties of hydrogels were investigated, where the morphological transformations and destabilization of hydrophobic domains resulted from a bilayer to a higher-order crystal structure. FINDINGS: Hydrophobic and hydrophilic cargos encapsulated in the dissipative assemblies (vesicles and injectable hydrogels) can be released in a controlled manner via changing the activation method. The reported adaptive materials engineered by dual activation steps are promising self-assembled systems for programmed release of loaded cargos at a tunable rate.

Bionic Poly(γ-Glutamic Acid) Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars.

Hypertrophic scarring (HS) remains a great challenge in wound dressing. Although various bionic extracellular matrix (ECM) biomaterials have been designed towards HS treatment, not all biomaterials can synergize biological functions and application functions in wound repair. Bionic scar-inhibiting scaffolds, loaded with biomolecules or drugs, become promising strategies for scarless skin regeneration. In this work, inspired by the physicochemical environment of ECM, a versatile fabrication of poly(γ-glutamic acid) based on electrospun photocrosslinkable hydrogel fibrous scaffolds incorporated with ginsenoside Rg3 (GS-Rg3) is developed for tissue repair and wound therapy. Decorated with adhesive peptide, bionic fibrous scaffolds can accelerate fibroblasts to sprout and grow, forming organized space-filling basement that gradually fills a depression before wound close up in the early stage. Additionally, by sustained release of GS-Rg3 in late stage, fibrous scaffolds promote scarless wound healing in vivo as evidenced by the promotion of cell communication and skin regeneration, as well as the subsequent decrease of angiogenesis and collagen accumulation. These ECM-inspired fibrous scaffolds, therefore, offer new perspectives on accelerated wound healing and tissue regeneration.

In situ photocrosslinked hyaluronic acid and poly (γ-glutamic acid) hydrogels as injectable drug carriers for load-bearing tissue application.

Due to the syringeability of precursor solution and convenience of open surgical treatment, injectable hydrogels have gained growing attention in drug delivery application. For load-bearing tissue, the excellent mechanical property is an important requirement for delivery vehicles to resist external stress and loads. Herein, we prepared mechanically robust injectable hydrogels (HA/γ-PGA hydrogels for short) using methacrylate-functionalized hyaluronic acid and poly (γ-glutamic acid) via photopolymerization. The HA/γ-PGA hydrogels showed outstanding anti-compression ability and could suffer a more than 80% strain. Meanwhile, after 5 cycles of compression, HA/γ-PGA hydrogels could still recover quickly against external stress, showing excellent shape recovery capability. Moreover, the mechanical properties could be modulated easily by changing the molar ratio of HA to γ-PGA. The drug release behavior was also evaluated and the drug-loaded HA/γ-PGA hydrogels showed a weak burst release and sustained release behavior. Additionally, HA/γ-PGA hydrogels also exhibited superior biocompatibility. Therefore, HA/γ-PGA hydrogels have great potential as injectable drug carriers for load-bearing tissue application.

Injectable hydrogels based on the hyaluronic acid and poly (γ-glutamic acid) for controlled protein delivery.

Injectable hydrogels have great potential in minimally invasive delivery. In this work, novel injectable hydrogels were prepared via self-crosslinking of aldehyde hyaluronic acid (HA-CHO) and hydrazide-modified poly (γ-glutamic acid) (γ-PGA-ADH) for proteins delivery. The HA/γ-PGA hydrogels could be formed in situ as fast as 9s with high swelling ratios. Rheological properties illustrated a wide processing range and good mechanical properties, which were reflected by broad linear viscoelastic region and higher threshold shear stress (σc) and storage modulus (G'). Meanwhile, the gelation time, swelling ratio, rheological properties, as well as the protein release behavior could be modulated conveniently. Bovine serum albumin (BSA) was designed as a model drug to study the release behavior. We found that the release mechanisms were either diffusion or Case-II relaxation depending on the different hydrogel components. The HA/γ-PGA hydrogels also showed good biocompatibility. Therefore, the HA/γ-PGA hydrogels have great potential as promising injectable biomaterials for controlled protein delivery.