Targeted Protein Fate Modulating Functional Microunits Promotes Intervertebral Fusion

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Biology

Background:

• Stable regulation of protein fate is crucial for bone tissue repair.
• USP26 stabilizes beta-catenin, promoting osteogenic activity and bone regeneration.
• In vivo delivery of USP26 is inefficient, hindering its therapeutic application.

Purpose of the Study:

• To develop an efficient delivery system for USP26 to enhance bone regeneration.
• To investigate the efficacy of a 3D-printed functional microunit (PFFM) for bone defect repair.

Main Methods:

• Constructing a PFFM using 3D printing and microfluidic technology.
• Encapsulating bone marrow mesenchymal stem cells (BMSCs) overexpressing USP26 within GelMA microspheres.
• Seeding these microspheres into PCL 3D-printed scaffolds to create the PFFM.

Main Results:

• The PFFM created a supportive microenvironment for BMSCs, promoting cell adhesion and activity.
• USP26 supplementation via PFFM stabilized beta-catenin, enhancing osteogenic phenotypes in BMSCs.
• In vivo studies demonstrated that PFFM significantly accelerated intervertebral bone fusion.

Conclusions:

• The PFFM system offers an effective strategy for delivering USP26 to promote bone tissue repair.
• This approach holds potential for treating challenging bone defects, including intervertebral fusion.
• PFFM presents promising clinical translational potential for bone regeneration therapies.