A biomimetic collagen-bone granule-heparan sulfate combination scaffold for BMP2 delivery

Bone morphogenetic protein 2 (BMP2)-induced bone regeneration is most efficacious when a carrier can deliver the growth factor into the defect site while minimizing off-target effects. The control of BMP2 release by such carriers is proving one of the most critical aspects of BMP2 therapy. Thus, increasing numbers of biomaterials are being developed to satisfy the simultaneous need for sustained release, reduced rates of degradation and enhanced activity of the growth factor. Here we report on a biomimetic scaffold consisting of bovine collagen type I, bone granules (Intergraft™), and heparan sulfate with increased affinity for BMP2 (HS3). The HS3 and collagen were complexed and then crosslinked via a simple dehydrothermal method. When loaded with a clinically relevant amount of BMP2 (1.25 mg/cc), the HS3-functionalised scaffolds were able to retain up to 58% of the initial amount of BMP2 over 27 days, approximately 3-fold higher than scaffolds without HS3. The bioactivity of the retained BMP2 was confirmed by gene expression in myoblast cells (C2C12) cultured on the scaffolds under osteogenic stimulation. Together these data demonstrate the efficacy of HS3 as a material to improve the performance collagen/bone granule-based scaffolds.