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

Abstract

The regeneration of large bone defects is a common and significant clinical problem. Limitations associated with existing treatments such as autologous bone grafts and allografts have increased the need for synthetic bone graft substitutes. The objective of this study was to evaluate the capacity of novel hollow hydroxyapatite (HA) microspheres to serve as a carrier for controlled release of bone morphogenetic-2 (BMP2) in bone regeneration. Hollow HA microspheres (106–150 μm) with a high surface area (>100 m2/g) and a mesoporous shell wall (pore size 10–20 nm) were created using a glass conversion technique. The release of BMP2 from the microspheres into a medium composed of diluted fetal bovine serum in vitro was slow, but it occurred continuously for over 2 weeks. When implanted in rat calvarial defects for 3 or 6 weeks, the microspheres loaded with BMP2 (1 μg/defect) showed a significantly better capacity to regenerate bone than those without BMP2. The amount of new bone in the defects implanted with the BMP2-loaded microspheres was 40% and 43%, respectively, at 3 and 6 weeks, compared to 13% and 17%, respectively, for the microspheres without BMP2. Coating the BMP2-loaded microspheres with a biodegradable polymer, poly(lactic-co-glycolic acid), reduced the amount of BMP2 released in vitro and, above a certain coating thickness, significantly reduced bone regeneration in vivo. The results indicate that these hollow HA microspheres could provide a bioactive and osteoconductive carrier for growth factors in bone regeneration.

Preparation and characterization of gelatin–hydroxyapatite composite microspheres for hard tissue repair

“…The G-HA group was similar to the clinical OS group, but exhibited denser and stronger structures than those of the OS group. A higher percentage of the bone island was present in the G-HA scaffold, which revealed greater osteoconductivity than either F or OS treatment [38][39][40]. Fig.…”

Controlled‐release of bone morphogenetic protein‐2 from a microsphere coating applied to acid‐etched Ti6AL4V implants increases biological bone growth in vivo

“…Our results are supported by previous in vivo studies that demonstrated the bone regeneration effect of BMP-2. Xiao et al 23 used BMP-2 loaded hollow hydroxyapatite microspheres coated with PLGA to repair calvarial defects of rats, inducing significantly enhanced bone regeneration. Similar findings were revealed in studies on rats, [36][37] mice, 24 and sheep.…”

“…[16][17][18] Recently, an enhanced effect of BMP-2 on bone regeneration was in animal studies. [23][24][25][26] In a previous study, we achieved sustained release (over $1 month) of rhBMP-2 from rhBMP-2-loaded poly(-lactic-co-glycolic acid) (PLGA) microspheres. 27 Alkyl cyanoacrylates are used as biological adhesives due to convenience, excellent bond strength, and rapid solidification.…”

Hollow calcium silicate microspheres with a micro-porous structure for protein adsorption and local delivery

“…Recently, microspheres have been proposed as a means of local drug delivery and have achieved markedly elevated pharmacological effects while minimizing systemic administrationassociated toxic effects [2,3]. In the field of bone-related materials, an ideal system for bone regeneration should simultaneously function as a controlled local delivery device for drugs or growth factors and as an osteoconductive graft to support bone formation [4,5].…”