Development of a multifunctional lncMALAT1-activated collagen-nanohydroxyapatatite scaffold to enhance the repair of large critical sized bone defects.

• Grant number: 24/23670-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: June 20, 2025
• End date: June 19, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Amanda Fantini de Camargo Andrade
• Supervisor: Fergal O'Brien
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Royal College Of Surgeons In Ireland, Ireland
• Associated to the scholarship: 22/14409-7 - Bone regeneration: Biomimetic nanocarriers from cell membranes to delivery lncRNA, BP.DR

Abstract

Repairing large or non-healing bone defects is challenging and often expensive. Biomimetic materials, such as collagen-nanohydroxyapatite (Coll-nHA) scaffolds, effectively promote bone repair and osteogenesis. To address larger critical-sized defects, advanced materials are necessary to enhance the interplay between angiogenesis and osteogenesis. Long non-coding RNAs, particularly lncMALAT1, are crucial in promoting these processes, presenting innovative therapeutic potential. The main objective of this study is to develop a lncMALAT1-activated Coll-nHA scaffold to enhance osteogenesis and angiogenesis for repairing larger, complex bone defects. This involves manufacturing Coll-nHA scaffolds with nHA nanoparticles for localized, controlled delivery of plasmid DNA encoding lncMALAT1 into mesenchymal stem cells (MSCs). Scaffolds will be manufactured, characterized, and optimized using protocols from the Tissue Engineering Research Group (TERG) at the Royal College of Surgeons in Ireland (RCSI). The initial assessment will focus on the effective delivery of lncMALAT1 to MSCs using Coll-nHA scaffolds. Subsequent in vitro analyses will focus on the scaffolds' ability to promote osteogenic and angiogenic processes, assessing classical markers like alkaline phosphatase (ALP), Vascular Endothelial Growth Factor (VEGF), and Hypoxia-Inducible Factor 1-alpha (HIF-1¿). This study combines biomaterial development with gene therapy to create "off-the-shelf" therapies for improved treatment of bone defects and clinical outcomes. The project is a collaboration between UNESP (Brazil) and RCSI (Ireland), funded by FAPESP, aimed at fostering future research partnerships