A hydrogel carrying Lycium barbarum glycopeptide was associated with faster and more organized wound repair in mice. The loaded gel showed the most sustained reduction in remaining wound area, while tissue samples showed an early shift in immune markers and later changes in collagen and other matrix-remodeling signals. The findings come from cell experiments, laboratory tests of the material and a mouse wound comparison.
The authors' premise was that keeping LbGp at the wound site in a hydrogel depot might improve retention and controlled release while supporting an early immune response and the later rebuilding of the extracellular matrix, or ECM. The formulation used LbGp at 10 mg/mL in the hydrogel precursor. For animal testing, it was made into cylindrical patches 5 mm across and 1 mm thick.
A material that responds to acidity
One of the material's defining features appeared in release tests. From day 1 through day 15, cumulative LbGp release was consistently higher at pH 5.0 than at pH 7.4. At the more acidic setting, the gel also showed swelling, a porous structure and greater disruption of its network. It behaved like a solid under the test conditions and recovered after mechanical stress.
Cell tests offered a second piece of the picture. RAW 264.7 macrophages and HaCaT keratinocytes showed predominantly viable staining and increasing viability readouts. In a scratch assay, which measures how quickly cells close a gap in a cell layer, HaCaT cultures exposed to the loaded gel showed greater closure than cells exposed to blank OSA/Gel at both 12 and 24 hours.
The mouse wound test
The animal comparison used five groups assigned by a random-number method: untreated wound control, free LbGp, Hydrosorb Gel, blank OSA/Gel and OSA/Gel@LbGp. Each group contained six mice. Across a 14-day comparison, the loaded gel showed the most sustained reduction in residual wound area and higher closure rates at multiple time points. Histology, the microscopic assessment of tissue structure, showed a smaller granulation-tissue gap as early as day 4 and the smallest gap by day 14, alongside more organized architecture.
That result coincided with a change in the early inflammatory niche. At day 4, wound tissue and LPS-stimulated macrophages exposed to OSA/Gel@LbGp had lower TNF-alpha and IL-1beta signals, while TGF-beta1 and ARG-1, markers associated in the study with reparative macrophage activity, were higher. The marker pattern is an association within the experiment, not proof that macrophage changes drove healing.
What changed in the tissue
The researchers then looked at gene activity in wound tissue to examine whether the later repair pattern involved the ECM. RNA sequencing at day 10 compared control and OSA/Gel@LbGp tissue using three biological replicates per group. It identified 2,097 upregulated genes and 980 downregulated genes in treated wounds, with enrichment in ECM-receptor interaction, cell-matrix adhesion, cytokine and signaling pathways, and matrix-remodeling processes. Mmp11 was highlighted as one remodeling-associated node.
By day 14, OSA/Gel@LbGp had the highest relative collagen content, higher MMP11 and VEGF signals, and lower MMP9 than untreated and blank-gel groups. MMP11 signals appeared near K14-positive epidermal areas and F4/80-positive macrophage-enriched areas. The analysis also found ECM-receptor interaction enrichment, more extensive collagen I signals and altered SMAD2/SMAD3 phosphorylation and SMAD7 expression. These observations accompanied ECM reconstruction, but the authors stated that they did not establish a linear causal cascade.
Why the result remains preliminary
Several limits make the findings preliminary. The wound model was acute and murine, so it cannot stand in for all clinically relevant wound settings. The acidic release comparison was performed in vitro, without showing how wound pH or local release changed in living animals. The bulk RNA-seq comparison did not fully separate the effects of the glycopeptide, the matrix and the delivery method. The study also used a total LbGp preparation rather than defined subfractions, leaving its composition and batch standardization unresolved. Long-term safety, dose-release-efficacy relationships and scar quality were not established.
Paper data and sources
Original title: pH-responsive hydrogel delivery of Lycium barbarum glycopeptide coordinates immune-matrix crosstalk to enhance wound healing
Authors: Lai S, Lei S, Zeng C et al.
Journal/Repository: Drug delivery
Status: Peer-reviewed
First online: 2026-10-19
DOI: Not available
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