Development of Bioprinted Xenografts with Methacrylated Tilapia Collagen Functionalized with Proanthocyanidins for Applications in Gingival Regeneration

• Grant number: 25/08776-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2025
• End date: February 28, 2029
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Juliano Milanezi de Almeida
• Grantee: Ruan Henrique Delmonica Barra
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Gingival recessions represent a common clinical challenge, particularly in esthetic areas, and their standard treatment with connective tissue grafts is associated with limited donor tissue availability and morbidity at the palatal site. In this context, alternative biomaterials with regenerative properties and good tissue integration have been investigated. Type I collagen of marine origin (tilapia) demonstrates excellent biocompatibility, low immunogenic risk, and sustainability. Its chemical modification with methacrylic anhydride (ColMA) enables in situ photopolymerization, providing greater control over biomaterial stability after application. The association with proanthocyanidins (PAs)-natural flavonoids with antioxidant properties and the ability to induce collagen cross-linking-may enhance the enzymatic resistance of the matrix and stimulate tissue regeneration. Therefore, this project proposes the development of a ColMA-based biomaterial derived from tilapia skin and functionalized with PAs for use as a xenograft in mucogingival surgeries. Initially, collagen will be extracted and methacrylated to establish ColMA as the base biomaterial (Phase 1). Next, bioactive concentrations of proanthocyanidins will be determined, aiming for collagen modulation without cytotoxicity to gingival fibroblasts (Phase 2). The third phase will include the formulation and characterization of functionalized ColMA hydrogels, focusing on the effective release of the selected bioactive concentrations (Phase 3). Subsequently, an extrusion-based bioprinting technology will be established to produce porous grafts from the optimal formulations (Phase 4). Finally, the therapeutic potential of the most promising biomaterial will be evaluated in vivo in a Wistar rat model of gingival recession and cutaneous wounds, through histological, immunohistochemical, and macroscopic analyses (Phase 5). (AU)