Mussel-Inspired Surface Immobilization of Heparin on Magnetic Nanoparticles for Enhanced Wound Repair via Sustained Release of a Growth Factor and M2 Macrophage Polarization.

Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (Fe3O4) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF). Herein, based on the Fe3O4 nanoparticle, we developed a fibroblast growth factor (bFGF)-loaded Fe3O4 nanoparticle using a simple mussel-inspired surface immobilization method. This nanoparticle, named as bFGF-HDC@Fe3O4, could stabilize bFGF in various conditions and exhibited sustained release of bFGF. In addition, an in vitro study discovered that bFGF-HDC@Fe3O4 could promote macrophage polarization toward an anti-inflammatory (pro-healing) M2 phenotype especially under eMF. Further, in vivo full-thickness wound animal models demonstrated that bFGF-HDC@Fe3O4 could significantly accelerate wound healing through M2 macrophage polarization and increased cell proliferation. Therefore, this approach of realizing sustained the release of the growth factor with magnetically macrophage regulating behavior through modification of Fe3O4 nanoparticles offers promising potential to tissue-regenerative applications.

Highly Water-Preserving Zwitterionic Betaine-Incorporated Collagen Sponges With Anti-oxidation and Anti-inflammation for Wound Regeneration.

A core problem in wound healing - with both fundamental and technological significance - concerns the rational design of bioactive and moist microenvironments. Here, we design a new class of zwitterionic betaine-incorporated collagen sponges (BET@COL) with integrated anti-oxidation and anti-inflammatory properties for promoting wound healing in a full-thickness wound model. The presence of zwitterionic betaine in a 3D network structure of collagen enables tightly bound and locked water molecules inside sponges via ionic solvation and confinement effect, while the integration of this amino acid also empowers the sponge with anti-oxidation and anti-inflammatory functions. In vitro results demonstrated that BET@COL collagen sponges strongly preserved water content up to 33.78 ± 0.78% at the 80th min at 37°C (only 0.44 ± 0.18% in control), and also exhibited high cell biocompatibility. Further, BET@COL collagen sponges with different betaine contents were applied to a full-thickness cutaneous wound model in mice, followed by a systematical evaluation and comparison of the effect of preserved water on wound healing efficiency in vivo. The optimal BET@COL collagen sponges were able to maintain high water content (e.g., moist microenvironment), suppress oxidative stress, improve anti-inflammation, all of which impose synergetic healing effects to promote wound closure, granulation formation, re-epithelization, collagen deposition and angiogenesis. This work demonstrates a new material as a promising candidate for wound dressing.

Silver crosslinked injectable bFGF-eluting supramolecular hydrogels speed up infected wound healing.

Topical wound dressings with various silver compositions that exhibit effective bacterial inhibition properties are often used to treat infected wounds. However, a silver dressing with no bioactive functionality will typically delay subsequent wound repair processes. Therefore, development of a simple wound dressing containing silver and loaded with a bioactive drug is a very attractive solution. Herein, we developed a silver crosslinked injectable chitosan-silver hydrogel as a silver immobilization matrix, loaded with basic fibroblast growth factor (bFGF) as its cargo (namely, bFGF@CS-Ag) for treatment of both acute and infected wounds. The in vivo results showed that bFGF@CS-Ag significantly enhanced infectious wound regeneration compared to that of acute wounds. Further investigation demonstrated that the improved wound repair by bFGF@CS-Ag was ascribed to the effectiveness of bacterial inhibition, the promotion of granulation formation, collagen deposition, neovascularization and re-epithelization, and to the reduction of the inflammatory response through promotion of M2 macrophage polarization. These results proved that the immobilization of silver in the hydrogel not only reduced the side effects of silver on the bioactivity of bFGF but also allowed elution of bFGF in a controlled release manner. Thus, this novel system has promising therapeutic potential for topical treatment of wounds.

Bioactive ECM Mimic Hyaluronic Acid Dressing via Sustained Releasing of bFGF for Enhancing Skin Wound Healing.

Successful dermal wound regeneration requires the coordination of repair cells and cellular signals with the extracellular matrix (ECM), which serves as an indispensable mechanical and biological supporter for cell functions and communications with varied cytokines during healing processes. Here, we developed an injectable bioactive wound dressing, methacrylated hyaluronic acid (Me-HA)-based hydrogel loading with basic fibroblast growth factor (bFGF), endowing the dressing with the pleiotropic bioactivity to mimic natural ECM. This bFGF@Me-HA dressing was applied to a mouse with full-thickness excisional wounds to investigate its positive roles in wound repair owing to the complementary functions of HA with sustained release of bioactive bFGF. Compared with the single Me-HA and bFGF group, bFGF@Me-HA hydrogel dressings significantly enhanced wound healing with accelerated re-epithelialization, granulation formation, collagen, deposition and skin appendage regeneration. Further investigations showed significantly promoted cell proliferation and vascularization in the bFGF@Me-HA group, which was mediated by the upregulation of transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) expressions. In conclusion, this bFGF@Me-HA hydrogel realized the optimization of simple ECM mimic dressing via introducing the bioactive effector, bFGF, and has the potential to be widely used as an effective bioactive ECM-based wound dressing in future wound care.