Microscopically Adaptable Bioink Guide Cell Compartmentalization toward Morphogenesis of a Functional...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Prevascularization remains a significant hurdle for large-scale tissue engineering applications.
• Existing engineered vasculature often fails to replicate the complex, multi-layered structure and function of natural blood vessels.
• Matrix dynamics are increasingly recognized as crucial for blood vessel development (vasculature morphogenesis).

Purpose of the Study:

• To develop an extracellular matrix-mimicking bioink capable of creating functional, prevascularized tissue constructs.
• To investigate the role of matrix dynamics and cellular signaling in engineered vasculature formation.
• To evaluate the therapeutic potential of the engineered vascular networks in preclinical models.

Main Methods:

• Fabrication of a novel bioink using an interpenetrated dynamic-covalent crosslinking strategy to mimic the extracellular matrix.
• Utilizing the bioink's adaptable microenvironment for functional compartmentalization of endothelial and smooth muscle cells.
• Investigating the focal adhesion kinase pathway's role in cellular organization and matrix interaction.
• Assessing the engineered vasculature's in vitro contractile function and in vivo performance in a mouse hind limb ischemia model.
• Evaluating the impact of implanted vascular networks on surrounding fibroblast survival and wound healing.

Main Results:

• The developed bioink successfully created adaptable microenvironments supporting cell compartmentalization, leading to histological vasculature configurations.
• The focal adhesion kinase pathway was identified as a key mediator, linking the adaptable microenvironment to vasculature organization via integrin-mediated adhesion and glycolysis.
• Engineered vasculature demonstrated in vitro contraction in response to angiotensin II.
• Significant improvement in blood perfusion was observed in a mouse hind limb ischemia model.
• Implanted vascular networks enhanced the survival and function of surrounding fibroblasts, promoting large full-thickness wound healing.

Conclusions:

• A one-step bioprinting strategy for prevascularization in designed architectures was successfully established.
• The novel bioink facilitates the creation of functional vascular tissue engineered constructs with therapeutic potential.
• This approach addresses a critical challenge in tissue engineering, paving the way for advanced regenerative therapies.