Bioorthogonal "Click Chemistry" Bone Cement Enables Pro-Translational Spinal Fusion in a Large Animal Sheep Model

Area of Science:

• Biomaterials Science
• Orthopedic Surgery
• Regenerative Medicine

Background:

• Spinal fusion commonly uses autografts, but these have limitations including donor site morbidity and limited supply.
• Developing effective bone graft substitutes is crucial for treating spinal instability and improving patient outcomes.

Purpose of the Study:

• To develop and evaluate an organic-inorganic nanohybrid cement (click-ON) as a bone graft substitute for spinal fusion.
• To assess the osteoinductivity and osteoconductivity of the click-ON cement in a preclinical model.

Main Methods:

• A poly(propylene fumarate) (PPF) based nanohybrid cement was synthesized using click chemistry (SPAAC).
• The cement was reinforced with nanohydroxyapatite (nHA) and microspheres containing rhBMP-2 and rhVEGF.
• The click-ON cement was tested in a sheep lumbar spinal fusion model, comparing it to autograft/rhBMP-2.

Main Results:

• Click-ON cement demonstrated successful spinal fusion with bridging bone formation in sheep after 6 months.
• Histology confirmed new bone deposition, host tissue integration, and significant vascular ingrowth.
• Immunohistochemistry showed co-localization of CD31 (angiogenesis) and ALP (osteogenesis), indicating coupled biological processes.

Conclusions:

• The click-chemistry-enabled PPF-based cement is a viable alternative to autografts for spinal fusion.
• The material exhibits excellent moldability, biological activity, and promotes functional fusion outcomes comparable to the gold standard.