Evaluation of bone regeneration in implants composed of hollow HA microspheres loaded with transforming growth factor β1 in a rat calvarial defect model

Abstract

Implants that serve simultaneously as an osteoconductive matrix and as a device for local growth factor delivery may be required for optimal bone regeneration in some applications. In the present study, hollow hydroxyapatite (HA) microspheres (106–150 μm) in the form of three-dimensional (3D) scaffolds or individual (loose) microspheres were created using a glass conversion process. The capacity of the implants, with or without transforming growth factor- 1 (TGF- 1), to regenerate bone in a rat calvarial defect model was compared. The 3D scaffolds supported the proliferation and alkaline phosphatase activity of osteogenic MLO-A5 cells in vitro, showing their cytocompatibility. Release of TGF- 1 from the 3D scaffolds into phosphate-buffered saline ceased after 2–3 days when 30% of the growth factor was released. Bone regeneration in the 3D scaffolds and the individual microspheres increased with time from 6 to 12 weeks, but it was significantly higher (23%) in the individual microspheres than in the 3D scaffolds (15%) after 12 weeks. Loading with TGF-β1 (5 μg/defect) enhanced bone regeneration in the 3D scaffolds and individual microspheres after 6 weeks, but had little effect after 12 weeks. 3D scaffolds and individual microspheres with larger HA diameter (150–250 μm) showed better ability to regenerate bone. Based on these results, implants composed of hollow HA microspheres show promising potential as an osteoconductive matrix for local growth factor delivery in bone regeneration.

Hollow hydroxyapatite microspheres: A novel bioactive and osteoconductive carrier for controlled release of bone morphogenetic protein-2 in bone regeneration

“…Our more recent work showed that loading the hollow HA microspheres with transforming growth factor beta 1 (TGFβ1) (5 μg/defect) can enhance bone regeneration in rat calvarial defects at 6 weeks but not at 12 weeks [15]. However, the amount of new bone formed in the defects implanted with the TGF-loaded microspheres was only ~20% of the total defect area after 6 or 12 weeks.…”

Towards the Development and Characterization of an Easy Handling Sheet-Like Biohybrid Bone Substitute

“…2,8,15,18 Our process, based on a parallelepipedic cell culture chamber and a CP granule monolayer, was thus efficient enough to promote the differentiation of the MC3T3 subclone 4 cells. It has been shown that the use of additional growth factors, such as transforming growth factor beta, bone morphogenetic protein, or fibroblast growth factors, may create complications during the clinical step, 55 with the need for accurate and precautionary validation for the patient's safety.…”

“…[6][7][8][9] Various materials have been studied and considered as possible scaffolds for in vitro bone ingrowth, such as ceramics, 10,11 polymers, 12,13 natural biomaterials such as silk or chitosan [14][15][16] or to a lesser extent metals, 7 and composites of these different groups. 17 Relevant shapes for the scaffold have also been debated, with different studies on granules and microspheres, 18 fibres, 19,20 hydrogels, 21 or engineered complex structures. 22,23 In addition, a bioreactor's ability to mimic in vivo environmental conditions is still an unsolved issue, with a wide variety of systems using mechanical stretching, flow perfusion, spinner flasks, rotating wall vessels, [24][25][26] or specifically designed chambers.…”

Enzyme-assisted calcium phosphate biomineralization on an inert alumina surface

“…A variety of biological molecules including carbohydrates, extracellular matrix (ECM) proteins or their components, e.g. arginine-glycine-aspartic acid (RGD) peptides and growth factors have been considered to elicit specific cellular responses, increase the interaction between the cells, material surfaces and tissues, and thereby result in integration and tissue regeneration [6][7][8][9].…”