Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Osteochondral interfaces exhibit continuous biological gradients.
• Engineering these gradients may enhance tissue regeneration.
• Controlled delivery of bioactive signals is crucial for scaffold fabrication.

Purpose of the Study:

• To develop a microsphere-based scaffold fabrication strategy for creating 3D tissue engineering scaffolds with spatially and temporally controlled delivery of bioactive signals.
• To investigate the potential of engineered signal gradients in promoting osteochondral tissue regeneration.

Main Methods:

• Utilized poly(D,L-lactic-co-glycolic acid) microspheres loaded with bone morphogenetic protein-2 and transforming growth factor-beta1.
• Fabricated gradient scaffolds with opposing gradients of these signals.
• Seeded scaffolds with human bone marrow stromal cells (hBMSCs) or human umbilical cord mesenchymal stromal cells (hUCMSCs).
• Assessed osteochondral tissue regeneration over a 6-week cell culture period.

Main Results:

• Gradient scaffolds produced regionalized extracellular matrix.
• Outperformed blank control scaffolds in cell number, glycosaminoglycan production, collagen content, and alkaline phosphatase activity.
• Showed enhanced gene expression of major osteogenic and chondrogenic markers in some instances.

Conclusions:

• Engineered signal gradients show promise for osteochondral tissue engineering.
• Spatially patterned gradients of biological cues can be achieved using microsphere-based scaffolds.
• This approach facilitates controlled delivery of bioactive signals for enhanced tissue regeneration.