Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment.

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.

CaP-based anti-inflammatory HIF-1α siRNA-encapsulating nanoparticle for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a common inflammatory disease and its treatment is largely limited by drug ineffectiveness or severe side effects. In RA progression, multiple signalling pathways, such as hypoxia-inducible factor (HIF)-1α, nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) pathways, act synergistically to maintain the inflammatory response. To downregulate HIF-1α, NF-κB, and MAPK expression, we proposed HIF-1α siRNA-loaded calcium phosphate nanoparticles encapsulated in apolipoprotein E3-reconstituted high-density lipoprotein (HIF-CaP-rHDL) for RA therapy. Here, we evaluated the potential of CaP-rHDL nanoparticles in RA therapy using a murine macrophage line (RAW 264.7) and a collagen-induced arthritis (CIA) mouse model. The CaP-rHDL nanoparticles showed significant anti-inflammatory effects along with HIF-1α knockdown and NF-κB and MAPK signalling pathway inhibition in lipopolysaccharide-activated macrophages. Moreover, they inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. In CIA mice, their intravenous administration resulted in high accumulation at the arthritic joint sites, and HIF-CaP-rHDL effectively suppressed inflammatory cytokine secretion and relieved bone erosion, cartilage damage, and osteoclastogenesis. Thus, HIF-CaP-rHDL demonstrated great potential in RA precision therapy by inhibiting multiple inflammatory signalling pathways.