Photo-crosslinkable hydrogel incorporated with bone matrix particles for advancements in dentin tissue engineering

Author(s)

da Silva, Isabela Sanches Pompeo ; Bordini, Ester Alves Ferreira ; Bronze-Uhle, Erika Soares ; de Stuani, Vitor ; Costa, Matheus Castro ; de Carvalho, Leticia Alves Martins ; Cassiano, Fernanda Balestrero ; de Azevedo Silva, Lucas Jose ; Borges, Ana Flavia Sanches ; Soares, Diana Gabriela

• Document type: Journal article
• Source: Journal of Biomedical Materials Research Part A; v. N/A, p. 16-pg., 2024-07-17.

Abstract

The objective of this study was to create injectable photo-crosslinkable biomaterials, using gelatin methacryloyl (GelMA) hydrogel, combined with a decellularized bone matrix (BMdc) and a deproteinized (BMdp) bovine bone matrix. These were intended to serve as bioactive scaffolds for dentin regeneration. The parameters for GelMA hydrogel fabrication were initially selected, followed by the incorporation of BMdc and BMdp at a 1% (w/v) ratio. Nano-hydroxyapatite (nHA) was also included as a control. A physicochemical characterization was conducted, with FTIR analysis indicating that the mineral phase was complexed with GelMA, and BMdc was chemically bonded to the amide groups of gelatin. The porous structure was preserved post-BMdc incorporation, with bone particles incorporated alongside the pores. Conversely, the mineral phase was situated inside the pore opening, affecting the degree of porosity. The mineral phase did not modify the degradability of GelMA, even under conditions of type I collagenase-mediated enzymatic challenge, allowing hydrogel injection and increased mechanical strength. Subsequently, human dental pulp cells (HDPCs) were seeded onto the hydrogels. The cells remained viable and proliferative, irrespective of the GelMA composition. All mineral phases resulted in a significant increase in alkaline phosphatase activity and mineralized matrix deposition. However, GelMA-BMdc exhibited higher cell expression values, significantly surpassing those of all other formulations. In conclusion, our results showed that GelMA-BMdc produced a porous and stable hydrogel, capable of enhancing odontoblastic differentiation and mineral deposition when in contact with HDPCs, thereby showing potential for dentin regeneration. Representative scheme of hydrogels fabrication. (Upper left) GelMA formulation. (Lower left) BMdc and BMdp fabrication process. (Right) Representation of GelMA-BMdc and GelMA-BMdp hydrogels. image (AU)

• FAPESP's process: 16/15674-5 - Association of tissue engineering techniques for mineralized tissue regeneration under degenerative inflammatory stimulus: analysis on 3D-culture perfusion bioreactor and animal inflammatory models
• Grantee: Diana Gabriela Soares dos Passos
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/09498-8 - Evaluation of bioprinted hydrogels containing decellularized bovine bone matrix applied for dentin regeneration
• Grantee: Isabela Sanches Pompeo da Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 22/05888-9 - Development of strategies for Regenerative Dentistry based on three-dimentional printing technologies
• Grantee: Diana Gabriela Soares dos Passos
• Support Opportunities: Regular Research Grants