Controlled Multiple Growth Factor Delivery from Bone Tissue Engineering Scaffolds via Designed Affinity

Abstract

It is known that angiogenesis plays an important role in bone regeneration and that release of angiogenic and osteogenic growth factors can enhance bone formation. Multiple growth factors play key roles in processes that lead to tissue formation/regeneration during natural tissue development and repair. Therefore, treatments aiming to mimic tissue regeneration can benefit from multiple growth factor release, and there remains a need for simple clinically relevant approaches for dual growth factor release. We hypothesized that mineral coatings could be used as a platform for controlled incorporation and release of multiple growth factors. Specifically, mineral-coated scaffolds were ''dip coated'' in multiple growth factor solutions, and growth factor binding and release were dictated by the growth factor-mineral binding affinity. Beta tricalcium phosphate (b-TCP) scaffolds were fabricated using indirect solid-free form fabrication techniques and coated with a thin conformal mineral layer. Mineral-coated b-TCP scaffolds were sequentially dipped in recombinant human vascular endothelial growth factor (rhVEGF) and a modular bone morphogenetic peptide, a mineral-binding version of bone morphogenetic protein 2 (BMP2), solutions to allow for the incorporation of each growth factor. The dual release profile showed sustained release of both growth factors for over more than 60 days. Scaffolds releasing either rhVEGF alone or the combination of growth factors showed an increase in blood vessel ingrowth in a dosedependent manner in a sheep intramuscular implantation model. This approach demonstrates a ''modular design'' approach, in which a controllable biologics carrier is integrated into a structural scaffold as a thin surface coating.

Adoption of nanodiamonds as biomedical materials for bone repair

“…This would in turn result in a sustained release of the peptide to promote bone formation. However, it has been shown that multiple growth factors or peptides should be delivered to mimic the natural process of bone healing [32][33][34]. Although the delivery of BMP-2 alone has been shown to advance bone production, the addition of other proteins can augment the process.…”

BMP-2-coated mineral coated microparticles improve bone repair in atrophic non-unions

“…The animals of the group MCM + BMP (n = 16) received also by direct injection MCM coated with approximately 13.7 µg BMP-2/ mg MCM. The dosage of BMP-2 was chosen based upon pre-experiments and an extensive literature search (Saito et al, 2003;Schmidmaier et al, 2002;Suárez-González et al, 2014;Kanczler et al, 2010). Finally, wound closure completed the surgical procedure.…”

Taking cues from the extracellular matrix to design bone-mimetic regenerative scaffolds

“…Because of the distinct functions mediated by BMPs, VEGF, and PDGF, delivery of combinations of these GFs constitutes a promising direction in the tissue engineering field [99]. Some of the prevalent GF combinations currently being investigated include: (1) BMP2 plus VEGF [100–104], which aims to promote both osteogenesis and angiogenesis, and (2) VEGF with either bFGF or PDGF [105–107]. The VEGF acts to stimulate activity of endothelial cells, while bFGF or PDGF attracts supporting pericytes to help stabilize the neovasculature.…”

“…The QK-coupled HA substrates stimulated endothelial cell proliferation and migration. This same HA-binding QK peptide was coated onto β-TCP disks and the disks were then implanted intramuscularly into sheep [104]. Disks with the anchored QK peptide stimulated significantly greater blood vessel ingrowth.…”