Neonatal and Adult Dermal Fibroblasts Remodel Hyaluronan Enriched Pericellular Matrix Differentially in Hyaluronic...

The goal of this study was to evaluate the impact of hyaluronic acid binding peptide (HABP) on pericellular matrix remodeling and to determine whether this effect differs between adult and neonatal fibroblasts. Neonatal wound healing is characterized by minimal scarring compared to adult healing, which typically results in fibrotic scar formation. Hyaluronic acid (HA) plays an important role in extracellular matrix organization and collagen remodeling during scarless healing. We hypothesized that HABP would promote endogenous HA retention around the pericellular matrix and influence collagen remodeling in fibroblasts.

Adult and neonatal human dermal fibroblasts were cultured in both two-dimensional and three-dimensional environments. HABP-tethered surfaces were used to promote HA retention around cells. Pericellular matrix formation and cell morphology were assessed in two-dimensional culture, while collagen contraction and collagen fibril morphology were evaluated in three-dimensional collagen gel systems.

Adult fibroblasts cultured on HABP surfaces appeared similar in shape to neonatal fibroblasts, suggesting that HABP could promote a more regenerative phenotype. Collagen contraction was steeper in peptide-tethered conditions than in control samples for both cell types. The presence of HABP increased contraction significantly in the presence of Hyaluronidase (HAdase). Collagen fibers exhibited altered width and organization in the presence of HABP and Scr-HABP compared with control samples.

These findings suggest that HABP enhances HA retention and alters collagen remodeling, supporting a pro-regenerative fibroblast remodeling response.