Spatio-temporal regulation of angiogenic sprouting patterns in regenerative processes

• Applicant: Dr. Julia Mehl
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567025345

Vascular remodeling and extracellular matrix (ECM) reorganization are fundamental to tissue regeneration, with bone healing serving as an exceptional model to study these processes due to its unique capacity for scar-free repair. Understanding the dynamics between ECM and angiogenesis is critical for advancing our understanding of regenerative processes. This project, to be conducted at the Tissue Microfabrication Lab at Boston University and the Harvard Wyss Institute, aims to develop a biomimetic in vitro platform to study the reciprocal crosstalk between vascular and ECM dynamics. The project is structured into three complementary work packages. Work Package 1 will establish vascular networks at different maturation stages using a microfluidic platform combined with engineered fibroblasts allowing to modulate VEGF and ANGPT1 expression. This approach enables precise control of vascular development, effectively replicating the varying gradients of vascular maturity observed during the early stages of bone healing. Work package 2 will investigate how ECM composition influences vascular development and remodeling. This will be achieved by using a CRISPR activation system to engineer fibroblasts capable of producing distinct ECM profiles, allowing precise and controlled studies of the impact of specific ECM compositions on vascular development and network formation. Work Package 3 will integrate chondrocytes into pre-vascularized scaffolds to model the transition to chondrogenesis, a critical step in scar-free bone healing. By examining how chondrocytes drive ECM remodeling and influence vascular remodeling, this work package will replicate key in vivo processes, offering valuable insights into the complex interplay between ECM dynamics, vascular remodeling, and chondrogenesis. This project leverages advanced microfluidic and synthetic biology tools to unravel the dynamic interactions between vasculature, ECM, and chondrocytes. The insights gained may guide the development of advanced regenerative strategies for bone healing and broader applications in angiogenesis-related diseases such as arthritis and cancer.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Christopher Chen