An injectable hydroxyapatite microsphere filler loaded with GHK-Cu tripeptide for anti-Inflammatory and antioxidant.
This study developed a novel injectable soft tissue filler by loading the GHK-Cu tripeptide (glycyl-L-histidyl-L-lysine copper complex) onto hydroxyapatite microspheres (HAPs), which were then combined with carboxymethyl cellulose, glycerol, and water to form a gel formulation called GHK-Cu@CMHA. The researchers report this is the first combination of HAPs and GHK-Cu designed to address implant-induced inflammation. The formulation demonstrated sustained GHK-Cu release over 7 days in laboratory testing, along with good flowability and injectability. Using a lipopolysaccharide (LPS)-induced inflammation model tested both in cell culture (in vitro) and in animals (in vivo), the study found that GHK-Cu@CMHA reduced levels of inflammatory cytokines and reactive oxygen species (ROS), while increasing superoxide dismutase (SOD) activity, suggesting antioxidant effects. Histological staining (H&E and Masson) indicated collagen deposition at treatment sites. Key limitations include the absence of human data, reliance on an LPS-induced inflammation model that may not fully replicate clinical filler complications, and no long-term safety or efficacy follow-up. These findings are preliminary and require further clinical validation before any conclusions about human benefit can be drawn.
Why this grade: The study combines in vitro cell-based assays and in vivo animal (LPS inflammation) models with no human participants, placing it firmly in the preclinical evidence category.
With the wide application of soft tissue fillers, implant material-induced inflammatory reactions have become a key factor affecting the therapeutic efficacy. This study developed an injectable filler with enhanced anti-inflammatory and antioxidant effects by adsorbing glycyl-L-histidyl-L-lysine copper complex (GHK-Cu) onto hydroxyapatite microspheres (HAPs), marking the first combination of HAPs and GHK-Cu to address inflammation caused by soft tissue fillers. GHK-Cu was successfully loaded onto HAPs by electrostatic adsorption. HAPs were then mixed with carboxymethyl cellulose (CMC), glycerol (GLY), and water to form GHK-Cu@CMHA gel. The study focus on the effective combination of HAPs as a carrier for sustained GHK-Cu delivery and the anti-inflammatory properties of GHK-Cu. GHK-Cu@CMHA exhibits sustained release properties for 7 days, which ensures prolonged therapeutic effects, minimizes peptide waste and reduces injection frequency, with good flowability and injectability. In the model of LPS-induced inflammation model in vivo and in vitro, GHK-Cu@CMHA gel reduced levels of inflammatory factors and Reactive oxygen species (ROS) levels decreased, while superoxide dismutase (SOD) activity was enhanced. In this process, H&E staining and Masson staining revealed significant collagen deposition. These findings further confirm that GHK-Cu@CMHA is a novel injectable soft tissue filler with good anti-inflammatory and antioxidant properties, which holds well potential for inflammation inhibition.
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