Biofabrication of biomimetic bone micro tissue - multicellular, dynamic and three-dimensional systems

• Grant number: 25/02004-0
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2026
• End date: January 31, 2029
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Katiúcia Batista da Silva Paiva
• Grantee: Katiúcia Batista da Silva Paiva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Alexandre Malta Rossi ; Andre Linhares Rossi ; Giuseppe Palmisano ; Hélder Almeida Santos ; José Mauro Granjeiro ; MONICA DIUANA CALASANS MAIA

Abstract

Our research group has been working on the characterization of osteoblastic differentiation of human dental pulp stem cells (DPSCs or SHEDs) and on new technologies for three-dimensional cell culture, specifically, spheroid models and microfluidic systems. Another aspect is the development of new biomaterials for bone regeneration and their association with these stem cells for the fabrication of engineered bone grafts for bone regeneration. In this context, this project comes to increase the results obtained in our last Regular Research Grant 2020/11564-6, with our objectives being to improve the osteogenic differentiation of mixed spheroids of DPSCs/SHEDs + macrophages and/or endothelial cells through direct and dynamic co-culture analyses, to understand the mechanisms of induction of osteogenic differentiation between DPSCs/macrophages/endothelial cells, to develop a biomimetic microfluidic system for bone repair and biomimetic bone micro tissue through spheroids embedded in hybrid hydrogel with natural crosslinker (type I collagen + chitosan + hyaluronic acid + carbonated nanohydroxyapatite). Thus, it is divided into 3 subprojects: (1) characterization of the interaction of mixed spheroids of DPSCs/SHEDs + macrophages + HUVECs in a dynamic system and secretome analysis (proteomics and exosome isolation); (2) application of spheroids + macrophages + HUVECs in the development of a biomimetic in vitro bone repair device; (3) characterization of spheroids + hybrid hydrogel with natural crosslinker. Finally, there will be validation in a preclinical model (critical defect of nude mouse calvaria). From basic research, we intend to apply the knowledge to the creation of innovative and validated in vitro platforms for the study of osteoimmunology and new bone biomaterials, in addition to the development of advanced therapy products for bone tissue based on bone engineering. Associated with this project, there is a PIPE 1 project under analysis for the development of bioink for 3D bioprinting from the same hybrid hydrogel with natural crosslinker. (AU)