Injectable functionalized-gelatin derived from cold-adapted species balances between arthroscopic extrudability prerequisite, chondrocompatibility and biomechanical requirements for precise arthroscopic restoration

Background & Aim Traumatic events leading to focal lesions in articular cartilage are an important cause of joint functionality deterioration, leading to physical inactivity and osteoarthritis. Although restorative and regenerative strategies utilizing different scaffolds seeded with chondrocytes or progenitor cells have been tested with partial success. Their indication is limited for small lesions and their mechanical insufficiency of the fibrocartilage can result in their degeneration overtime, requiring patients to be re-operated within two years. Treatment modalities that favor the application of rapidly-crosslinking biopolymeric solutions to reconstruct cartilage lesions via an arthroscopic approach are highly desirable to reduce risk, surgery time and post-operative recovery times. The desired features of the alternative materials for lesion restoration should match the mechanical properties of cartilage, mimic its mechanical behavior and exhibit satisfactory chondro-inductive capacity. Methods, Results & Conclusion In this work, a new methacrylamide-functionalized gelatin extracted from a cold-adapted species was evaluated as the principal biopolymer for a photo-curable and injectable formulation for cartilage restoration. Unlike using mammalian gelatin, the cold-adapted nature allowed the formulation of highly concentrated biopolymeric solutions (>35 % W/V), while maintaining arthroscopic extrudability and avoiding sol-gel transition at room temperature. The dense and interconnected network of biopolymers after photo-crosslinking showed similar stiffness to human cartilage (∼ 1 MPa), whereas the chondrocyte-laden biopolymeric network was capable to induce formation of cartilage tissue in vitro, presenting similar values to human cartilage in glycosaminoglycan (GAG) (∼ 2 µg/mg), mRNA collagen(Col)2A/Col1A mRNA ratio (∼7) and similar distribution of GAG and Col staining across the scaffold. Finally, precise arthroscopic restoration of a cartilage lesion has been proven in a 3D simulation model. The developed Injectable functionalized-gelatin formulation respond to all the suitability criteria for using the regeneration of functional hyaline cartilage of patients through minimally invasive procedures.