The objective of this study is to investigate the effect of collagen matrix with polydeoxyribonucleotide (PDRN) at two concentrations on keratinized tissue (KT) regeneration for buccally positioned implants in canines. Four implants were placed in the edentulous mandible of five dogs simultaneously with KT removal. The implants were positioned buccally with respect to the ridge crest. After 2 months, KT augmentation was performed applying the following treatment modalities:(1) free gingival graft (FGG), (2) xenogeneic collagen matrix (XCM), (3) XCM loaded with 2 mg/mL PDRN (PDRN2), and (4) XCM loaded with 4 mg/mL PDRN (PDRN4). All animals were sacrificed 3 months later. Outcomes included clinical (KT height) and histomorphometric measurements (KT height/length, level of the mucosa, mucosal thickness, supracrestal soft tissue height). Clinical and histomorphometric KT formation at 3 months was greatest in groups with FGG (4.70 ± 1.00/3.94 ± 0.93 mm) and PDRN2 (4.85 ± 1.43/3.95 ± 0.87 mm). Group PDRN2 (1.87 ± 1.50 mm) showed a higher marginal mucosal level with respect to the implant platform compared to other groups (range: 0.57 ± 0.97-0.69 ± 1.14 mm). All groups presented a soft tissue thickness of < 2 mm on the buccal aspect of the implants. Based on the limitations of this pilot preclinical study, XCM with 2 mg/mL of PDRN demonstrated a potential for KT augmentation.