Improvement of Bone Regeneration Capability of Ceramic Scaffolds by Accelerated Release of Their Calcium Ions

Abstract

To regenerate the bone tissue, the fabrication of scaffolds for better tissue regeneration has attracted a great deal of attention. In fact, growth factors are already used in clinical practice and are being investigated for enhancing the capacity for bone tissue regeneration. However, despite their strong osteoinductive activity, these growth factors have several limitations: safety issues, high treatment costs, and the potential for ectopic bone formation. The aim of this study was therefore to develop ceramic scaffolds that could promote the capacity for bone regeneration without growth factors. Three-dimensional ceramic scaffolds were successfully fabricated from hydroxyapatite (HA) and tricalcium phosphate (TCP) using projection-based microstereolithography, which is an additive manufacturing technology. The effects of calcium ions released from ceramic scaffolds on osteogenic differentiation and bone regeneration were evaluated in vitro and in vivo. The osteogenesis-related gene expression and area of new bone formation in the HA/TCP scaffolds was higher than those in the HA scaffolds. Moreover, regenerated bone tissue in HA/TCP scaffolds were more matured than that in HA scaffolds. Through this study, we were able to enhance the bone regeneration capacity of scaffolds not by growth factors but by calcium ions released from the scaffolds. Ceramic scaffolds developed in this study might be useful for enhancing the capacity for regeneration in complex bone defects.

Osteoinductive PolyHIPE Foams as Injectable Bone Grafts

“…Previous studies have reported a significant increase in calcium ion release and subsequent osteoclast-mediated resorption rate and new bone formation in response to scaffolds containing ACP compared to HA. 24,25 The aqueous solution of calcium chloride (1 wt%) and deionized water was then added to the organic phase (75% v) in six additions and mixed at 500 rpm for 2.5 min each to promote emulsification. The two HIPEs (BPO and TMA) were mixed at 2500 rpm for 30 s in the SpeedMixer to initiate crosslinking.…”

“…23 For this reason, many researchers have investigated the resorption rates of mixed calcium phosphate compositions with different percent crystallinities and assessed the effect on in vivo bone regeneration. 24,25 The relative ability of these calcium phosphate minerals to stimulate progenitor cell proliferation and differentiation is dependent on the physiological environment and presentation in the scaffold. In contrast, the demineralized bone matrix (DBM) stimulates bone growth by providing an environment in which invading progenitor and inflammatory cells are stimulated to release trophic cytokines to recruit cells for repair.…”

Therapeutically relevant aspects in bone repair and regeneration

“…The different ions can be structured during the thermal (sintering or quenching) processes of the ceramic scaffolds, direct incorporation of ionic compounds can be obtained for the biopolymer scaffolds. Some pioneering works have shown the release of different levels of Ca ions from collagen gels, showing different effects on cell behaviors [152]. Sr ions were also incorporated into carboxymethylcellulose hydrogels as a bone scaffold to enable ionic stimulation of cells for bone formation.…”

Variation of Hydroxyapatite Content in Soft Gelatin Affects Mesenchymal Stem Cell Differentiation

“…More recently, Liu et al indicated that nano-HA-coated magnetic nanoparticles increased cell viability and guided neuronal growth (Liu et al, 2015). The releasing of Ca 2+ from Biphasic calcium phosphate bioceramics has been reported previously (Gallinetti et al, 2014;Seol et al, 2014). It has been hypothesized that the releasing of Ca 2+ from the hydrogel activated the purinergic receptor of mesenchymal stem cells, which induced neuronal differentiation (Glaser et al, 2013).…”