Multimodality imaging reveals angiogenic evolution in vivo during calvarial bone defect healing

Area of Science:

• Regenerative Medicine
• Biomedical Imaging
• Skeletal Biology

Background:

• Calvarial bone defect healing involves complex interactions between blood vessel growth (angiogenesis) and bone formation (osteogenesis).
• Previous studies primarily focused on structural changes, lacking dynamic functional insights into vascular remodeling and its impact on bone regeneration.

Purpose of the Study:

• To develop and apply a novel multimodality imaging approach for longitudinal, dynamic characterization of vascular and osteogenic processes in calvarial defects.
• To investigate the temporal relationship between angiogenic evolution and de novo osteogenesis in a preclinical calvarial defect model.

Main Methods:

• Utilized multi-wavelength intrinsic optical signal (IOS) imaging for microvascular remodeling, oxygenation (SO2), and osteogenesis assessment.
• Employed laser speckle contrast (LSC) imaging to evaluate blood flow and vascular maturity.
• Used micro-computed tomography (μCT) for validating bone volumetric changes.

Main Results:

• Angiogenic evolution was tightly coupled with calvarial bone regeneration, correlating with distinct healing phases: injury, hematoma, revascularization, and remodeling.
• Significant in vivo changes in vascular morphology, blood flow, oxygenation, and maturity occurred within the first two weeks.
• Angiogenesis preceded osteogenesis, with bone formation significantly increasing only by four weeks.

Conclusions:

• Angiogenic evolution plays a critical role in modulating osteogenesis during calvarial bone healing.
• This multimodality imaging approach provides dynamic functional insights into bone regeneration.
• Findings may inform the development of improved tissue-engineering strategies for calvarial defects.