Background <p>Facial rejuvenation involves addressing the breakdown of collagen and elastin that occurs with aging. Hyaluronic acid (HA)-based dermal fillers have become a key non-invasive treatment, known for their volumizing effects and potential regenerative benefits. This study characterizes the physicochemical and rheological properties of Hylan Gel Dermal Filler DX, a novel filler combining HA and dextranomer microspheres, and evaluates its capacity to enhance extracellular matrix regeneration.</p> Methods <p>Rheological analysis was conducted to determine viscoelastic properties, including storage modulus (G'), loss modulus (G''), and tan delta across frequencies (0.1–10 Hz). In vitro experiments with normal human dermal fibroblasts (NHDFs) and monocytes (J774A.1) assessed the effects of Hylan Gel Dermal Filler DX (HA + DX), Genefill Soft Fill (HA), HarmonyCa® (HA+CaHa), Radiesse® (CaHa), and Sculptra® (PLLA). Hydration and wound healing assays were also performed. Biomarker analysis focused on collagen types I, III, IV, VI, elastin, and cytokines (TGF-β1, IL-1β, IL-6, IL-10, TNFα).</p> Results <p>Rheologically, HA + DX displayed a balanced elastic and viscous profile, supporting its structural integrity and adaptability in dynamic facial areas. HA + DX demonstrated high stimulation of collagen types I, III, IV, VI, and elastin production, with enhanced fibroblast migration and wound healing at 72 hours compared to other fillers. HA + DX also modulated cytokines, increasing TGF-β1 and IL-10 while reducing TNFα and IL-1β, suggesting anti-inflammatory and regenerative properties.</p> Conclusions <p>HA + DX exhibited considerable benefits in collagen stimulation, wound healing, and cytokine modulation. Its favorable rheological characteristics and regenerative potential make it a promising option for facial rejuvenation and tissue regeneration.</p> No Level Assigned <p>This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="http://www.springer.com/00266">www.springer.com/00266</a></p>