Development of pre-vascularized soft callus organoid-based constructs through micro- to Macro- vessel integration: enhancing implant survival and bone forming potential
Description: Critical-size bone defects pose a significant clinical challenge due to high non-union risk and grafts failure rate. Vascularization deficits are often seen in postmenopausal osteoporosis (PMOP), where it is a major cause of apoptosis in engineered bone grafts, thus limiting clinical effectiveness. Our hypothesis is that pre-vascularization enhances callus organoid-based constructs (COCs) survival and bone regeneration capacity by enabling rapid host-graft vascular anastomosis. In addition, larger scale implants can be engineered addressing a major limitation in the field. The study employs a developmental engineering approach. Callus organoids, pre-differentiated from human periosteum derived cells (hPDCs), will be encapsulated within a hydrogel containing endothelial cells to obtain COCs. With a microfluidic vessel-on-chip device, micro-to-Macro pre-vascularized COCs will be developed. Finally, The osteogenic capacity of those COCs will be screened subcutaneously, followed by orthotopic implantation to evaluate the therapeutic potential in both healthy and PMOP mice. This work provides a mechanistic framework for pre-vascularized COCs, with translational potential through Flanders’ REGMEDXB consortium and KU Leuven’s automated COs production platform (EU H2020 “Jointpromise”, grant number: 874837)
Funder: Fonds Wetenschappelijk Onderzoek
Funding type: grant
Funder scheme: FWO Strategic Basic Research Grant
Start date: 2025-11-01
End date: 2029-10-31
Investigators: Sijia Leng, Ioannis Papantoniou
Institution: FWO
Funded outputs count: 1
Funder award ID: 1SA4B26N
OpenAlex ID: G3007495076