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Maintaining periodontal and peri-implant soft tissues health is crucial for the long-term health of teeth and dental implants. New biomedical strategies aimed at avoiding connective tissue alterations and related diseases (e.g., periodontitis and peri-implantitis) are constantly evolving. Among these, collagen-based medical products have proven to be safe and effective. Accordingly, the aim of the present study was to evaluate the effects of Dental SKIN BioRegulation (Guna S.p.a., Milan, Italy), a new injectable medical device composed of type I collagen of porcine origin, on primary cultures of human gingival fibroblasts (hGF). To this end, hGF were cultured on collagen-coated (COL, 100 µg/2 mL) or uncoated plates (CTRL) before evaluating cell viability (24 h, 48 h, 72 h, and 7 d), wound healing properties (3 h, 6 h, 12 h, 24 h, and 48 h), and the activation of mechanotransduction markers, such as FAK, YAP, and TAZ (48 h). The results proved a significant increase in cell viability at 48 h (p < 0.05) and wound closure at 24 h (p < 0.001) of hGF grown on COL, with an increasing trend at all time-points. Furthermore, COL significantly induced the expression of FAK and YAP/TAZ (p < 0.05), thereby promoting the activation of mechanotransduction signaling pathways. Overall, these data suggest that COL, acting as a mechanical bio-scaffold, could represent a useful treatment for gingival rejuvenation and may possibly help in the resolution of oral pathologies. [ABSTRACT FROM AUTHOR]