This study presents a novel method to enhance the biocompatibility of decellularized porcine aortic segments while preserving their mechanical properties and histological structure. Detergent-decellularized aortic segments were treated with modified globular chitosan (Novochizol™) at varying concentrations (0.5%, 1%, 2%, and 3%) by sonication and subsequently subjected to mechanical testing. To further improve cell infiltration, blind-ended laser channels were created within the decellularized segments. The modified grafts were then seeded with porcine vascular interstitial cells in vitro for 7 days or implanted into the thoracic aorta of minipigs for 30 days. Histological analysis was performed at each stage of the study. Impregnation with Novochizol™ significantly increased the specific strength (from 0.97 ± 0.19 MPa to 4.99 ± 2.43 MPa) and Young's modulus (from 0.73 ± 0.06 MPa to 14.66 ± 7.14 MPa) of the decellularized aortic segments. Histological examination confirmed the preservation of the connective tissue matrix's morphological structure. Optimal modification conditions were identified as a 30 min sonication in a 1% Novochizol™ solution at 25 °C. A 35 ms continuous laser treatment was sufficient to create a 1 mm deep blind-ended channel, thereby promoting the seeding of vascular interstitial cells within the acellular graft, as confirmed by implantation in minipigs.