Bringing a Gene-Activated Bone Substitute Into Clinical Practice: From Bench to Bedside

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Gene Therapy

Background:

• Current bone grafting limitations necessitate advanced bone substitutes.
• Octacalcium phosphate and vascular endothelial growth factor gene delivery offer potential for enhanced bone regeneration.

Purpose of the Study:

• To develop and evaluate a gene-activated bone substitute for clinical bone grafting applications.
• To assess the safety and efficacy of this novel material in human patients.

Main Methods:

• Development of a gene-activated bone substitute using octacalcium phosphate and vascular endothelial growth factor plasmid DNA.
• Preclinical testing in rabbit cranial bone defects and an open-label clinical trial (NCT03076138) in 20 patients.
• Evaluation of bone formation via computed tomography and histological analysis, alongside safety monitoring for adverse events.

Main Results:

• The gene-activated bone substitute demonstrated no cytotoxicity and prolonged gene delivery in preclinical models.
• Clinical trial showed no adverse events or serious adverse events in 20 patients over 30 months.
• All patients exhibited newly formed bone tissue with high bone density (908.13 ± 114.40 HU) and successful integration of the material with host bone.

Conclusions:

• The gene-activated bone substitute is a feasible, safe, and effective material for jaw bone grafting.
• This represents the first gene-activated bone substitute successfully translated from preclinical research to clinical application.
• The material promotes bone regeneration through angiogenesis induction and integrates well with host bone without fibrous encapsulation.