Novel Approaches Guiding the Future of Spinal Biologics for Bone Regeneration

Despite the continued growth of spine fusion procedures, the ideal material for bone regeneration remains unclear. Current bone graft substitutes and extenders in use such as exogenous BMP-2 or demineralized bone matrix and hydroxyapatite either have serious complications associated with use or lead to clinically significant rates of non-union. The introduction of nanotechnology and 3D printing to regenerative medicine facilitates the development of safer and more efficacious bone regenerative scaffolds that present solutions to these problems. Many researchers in orthopedics recognize the importance of lowering the dose of recombinant growth factors like BMP-2 to avoid the complications associated with its normal required supraphysiologic dosing to achieve high rates of fusion in spine surgery.

Recent iterations of bioactive scaffolds have moved towards peptide amphiphiles that bind endogenous osteoinductive growth factor sources at the site of implantation. These molecules have been shown to provide a highly fluid, natural mimetic of natural extracellular matrix to achieve 100% fusion rates at 10-100 times lower doses of BMP-2 relative to controls in pre-clinical animal posterolateral fusion models. Alternative approaches to bone regeneration include the combination of existing natural growth factor sources like human bone combined with bioactive, biocompatible components like hydroxyapatite using 3D-printing technologies. Their elastomeric, 3D-printed scaffolds demonstrate an optimal safety profile and high rates of fusion (~92%) in the rat posterolateral fusion model. Bioactive peptide amphiphiles and developments in 3D printing offer the promising future of a recombinant growth factor- free bone graft substitute with similar efficacy but improved safety profiles compared to existing bone graft substitutes.