Divergent effects of premineralization and prevascularization on osteogenesis and vascular integration in humanized tissue engineered bone constructs

Sugandha Bhatia ¹, Luke Hipwood ², Briony Claxton ³

¹School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, 4102, Australia; Max Planck Queensland Centre on the Materials Science for Extracellular Matrices, QUT, Brisbane, QLD, 4059, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4059, Australia; Translational Research Institute (TRI), Brisbane, QLD, 4102, Australia.
²School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, 4102, Australia; Max Planck Queensland Centre on the Materials Science for Extracellular Matrices, QUT, Brisbane, QLD, 4059, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4059, Australia.
³School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, 4102, Australia; Translational Research Institute (TRI), Brisbane, QLD, 4102, Australia.
⁴Max Planck Queensland Centre on the Materials Science for Extracellular Matrices, QUT, Brisbane, QLD, 4059, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4059, Australia.
⁵Translational Research Institute (TRI), Brisbane, QLD, 4102, Australia.
⁶Division of Animal Genetics, Laboratory Animal Research Centre, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Genome Engineering, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁷School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, 4102, Australia; Max Planck Queensland Centre on the Materials Science for Extracellular Matrices, QUT, Brisbane, QLD, 4059, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4059, Australia; Translational Research Institute (TRI), Brisbane, QLD, 4102, Australia; ARC Training Centre for Cell and Tissue Engineering Technologies, QUT, Brisbane, QLD, 4000, Australia. Electronic address: jacqui.mcgovern@qut.edu.au.

⁰School of Biomedical Sciences, Faculty of Health, QUT, Brisbane, QLD, 4102, Australia; Max Planck Queensland Centre on the Materials Science for Extracellular Matrices, QUT, Brisbane, QLD, 4059, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4059, Australia; Translational Research Institute (TRI), Brisbane, QLD, 4102, Australia.

Acta Biomaterialia +

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June 13, 2025

View abstract on PubMed

Summary

Pre-mineralization enhances bone formation in engineered bone constructs, while pre-vascularization promotes blood vessel integration. Combining these techniques in humanized tissue-engineered bone constructs (hTEBCs) offers insights for regenerative therapies.

Area Of Science

Biomaterials Science
Tissue Engineering
Regenerative Medicine
Vascular Biology
Osteogenesis Research

Background

Osteogenesis and vascularization are critical, interconnected processes in bone formation.
Humanized tissue-engineered bone constructs (hTEBCs) aim to mimic the bone microenvironment.
Prevascularization of hTEBCs may enhance vascular integration and osteogenic capacity.

Purpose Of The Study

To investigate the effects of pre-mineralization and pre-vascularization on bone and vasculature development in an ectopic hTEBC model.
To evaluate a scaffold-hydrogel composite approach for creating functional hTEBCs.
To understand the distinct contributions of pre-mineralization and pre-vascularization in bone tissue engineering.

Main Methods

Human osteoblast cells (hOBs) were cultured with or without a mineralization boost (OM+) in osteogenic conditions.
Photocrosslinkable fish gelatin hydrogels were used to promote vascular network formation in vitro.
Constructs were implanted subcutaneously into immunocompromised rats, creating four experimental groups (OM, OM+, OM/Vas, OM+/Vas).

Main Results

Pre-mineralization (OM+) accelerated osteoinduction and enhanced osteogenic differentiation in vivo, forming woven bone.
Pre-vascularization (OM/Vas, OM+/Vas) reduced bone volume but promoted human endothelial network development and host vasculature anastomosis.
Distinct contributions of pre-mineralization for bone formation and pre-vascularization for vascular integration were highlighted.

Conclusions

Pre-mineralization is crucial for robust bone formation in hTEBCs.
Pre-vascularization is essential for enhancing vascular integration within engineered bone.
This study provides insights for advancing the physiological relevance of hTEBC models and designing biomaterials for regenerative therapies.

Keywords:

Bone Humanized bone model Mineralization Osteogenesis Rat model Tissue humanisation Vasculature