Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs
Ana Catarina Sousa, Rui Alvites, Bruna Lopes, Patrícia Sousa, Alícia Moreira, André Coelho, Alexandra Rêma, Sara Biscaia, Rachel Cordeiro, Fátima Faria, Gabriela Fernandes da Silva, Irina Amorim, José D. Santos, Luís Atayde, Nuno Alves, Marco Domingos, Ana Colette Maurício
Abstract
Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment . This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering. • Bone tissue regeneration remains a significant challenge in clinical settings . • This study proposes a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. • Rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col) is produced. • In vitro results demonstrated that the hybrid scaffolds presented significantly higher cell viability. • In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration.