Directed vascularization in bone regeneration requires bone marrow reconstitution

Mehl, Julia; Thiele, Tobias; Ellinghaus, Agnes; Gerhardt, Holger; Duda, Georg N.

Directed vascularization in bone regeneration requires bone marrow reconstitution

Tools

Preview	PDF (Publisher's Version) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader 4MB
	MS Word (Supplementary Data) 4MB

Item Type:	Article
Title:	Directed vascularization in bone regeneration requires bone marrow reconstitution
Creators Name:	Mehl, Julia, Thiele, Tobias, Ellinghaus, Agnes, Gerhardt, Holger and Duda, Georg N.
Abstract:	Bone has the unique ability to regenerate without scarring, yet the cellular dynamics and directional organization underlying this process, and how they are linked to marrow reconstitution, remain incompletely understood. To investigate these mechanisms, we developed a novel double osteotomy model in mice, involving transplantation of a 2-mm bone graft between genetically distinct fluorescent reporter lines (yellow fluorescent protein and red fluorescent protein). This approach enabled precise tracking of cellular migration and vascularization over 3, 7, and 14 d post-transplantation. Our findings revealed directed migration of host-derived proximal bone marrow cells into the graft, starting at day 3 and leading to complete host cell infiltration by day 14. CD146-positive blood vessels, mainly originating from the proximal host marrow, invaded the graft coinciding with graft marrow remodeling. Marrow disintegration within the graft occurred prior to vascular and cellular invasion, with subsequent reconstitution progressing from the proximal side. Flushing the graft marrow cavity prior to transplantation resulted in more extensive marrow niche formation by day 14 suggesting that marrow reconstitution can proceed more rapidly without the need for prior remodeling. This study introduces a new model to dissect the spatial and temporal coordination of cellular migration and vessel invasion during bone regeneration. Our results uncover the directional nature of healing and underscore the critical role of marrow reconstitution in guiding regenerative processes—insights that may inform surgical and biomaterial strategies to enhance bone repair.
Keywords:	Bone Healing, Bone Graft Transplantation, Bone Marrow Reconstitution, Directed Healing, Directed Vascularization, Animals, Mice
Source:	JBMR Plus
ISSN:	2473-4039
Publisher:	Oxford University Press / American Society for Bone and Mineral Research
Volume:	9
Number:	12
Page Range:	ziaf162
Date:	December 2025
Official Publication:	https://doi.org/10.1093/jbmrpl/ziaf162
PubMed:	View item in PubMed

Repository Staff Only: item control page

Download Statistics

Downloads

Downloads per month over past year