Local microarchitecture affects mechanical properties of deposited extracellular matrix for osteonal regeneration.

Multiple biomimetic approaches have been attempted to accelerate the regeneration of functional bone tissue. While most synthetic scaffolds are designed to mimic the architecture of trabecular bone, in the current study, cortical bone-like extracellular matrix was regenerated in vitro within organized structures. Biphasic calcium phosphate (BCaP) and hydroxyapatite (HAp) scaffolds were developed with longitudinal microchannels (250 µm diameter) that resembled native osteons in cortical bone. BCaP and HAp scaffolds had a compressive strength of 7.61±1.42 and 9.98±0.61 MPa respectively. The constructs were investigated in vitro to evaluate the organization and stiffness of the extracellular matrix (ECM) formed by human fetal osteoblasts (HFObs) cultured inside the microchannels. The ECM deposited on the BCaP scaffolds was found to have a higher micro-hardness (h) (1.93±0.40 GPa) than the ECM formed within the HAp microchannels (h=0.80±0.20 GPa) (p<0.05) or native bone (h=0.47-0.74 GPa). ECM deposition within the microchannels resembled osteoid organization and showed a significant increase in both osteoid area and thickness after 24 days (p<0.001). These observations indicate that controlled microarchitecture, specifically cylindrical microchannels, plays a fundamental role in stimulating the appropriate cellular response aimed at recreating organized, cortical bone-like matrix. These findings open the door for researchers to develop a new generation of cortical bone scaffolds that can restore strong, organized bone.

Effect of cell-seeded hydroxyapatite scaffolds on rabbit radius bone regeneration.

Highly porous hydroxyapatite (HA) scaffolds were developed as bone graft substitutes using a template coating process, characterized, and seeded with bone marrow-derived mesenchymal stem cells (BMSCs). To test the hypothesis that cell-seeded HA scaffolds improve bone regeneration, HA scaffolds without cell seeding (HA-empty), HA scaffolds with 1.5 × 10(4) BMSCs (HA-low), and HA scaffolds with 1.5 × 10(6) BMSCs (HA-high) were implanted in a 10-mm rabbit radius segmental defect model for 4 and 8 weeks. Three different fluorochromes were administered at 2, 4, and 6 weeks after implantation to identify differences in temporal bone growth patterns. It was observed from fluorescence histomorphometry analyses that an increased rate of bone infiltration occurred from 0 to 2 weeks (p < 0.05) of implantation for the HA-high group (2.9 ± 0.5 mm) as compared with HA-empty (1.8 ± 0.8 mm) and HA-low (1.3 ± 0.2 mm) groups. No significant differences in bone formation within the scaffold or callus formation was observed between all groups after 4 weeks, with a significant increase in bone regenerated for all groups from 4 to 8 weeks (28.4% across groups). Although there was no difference in bone formation within scaffolds, callus formation was significantly higher in HA-empty scaffolds (100.9 ± 14.1 mm(3) ) when compared with HA-low (57.8 ± 7.3 mm(3) ; p ≤ 0.003) and HA-high (69.2 ± 10.4 mm(3) ; p ≤ 0.02) after 8 weeks. These data highlight the need for a better understanding of the parameters critical to the success of cell-seeded HA scaffolds for bone regeneration.

A cellular perspective to bioceramic scaffolds for bone tissue engineering: the state of the art.

A vast number of manufacturing techniques have been employed in the last five years to manufacture three dimensional (3D) calcium phosphate (CaP) scaffolds, with the intention to replicate the architecture of native bone as well as to repair and restore bone function. Design features such as architectural control and sintering temperature and their impact on scaffold performance is presented in this review. In vitro cell responses to bioceramic scaffolds and their in vivo performances have been enhanced. Current frontiers of active research on HA scaffolds have included the relationship between fluid flow and mechanotransduction as well as cell signaling pathways that induce endothelial cell recruitment and angiogenesis. Additionally, current research has focused on a better understanding of cell signaling and its environmental cues. The availability of non-invasive and non-destructive quantitative imaging modalities has also become critical in aiding the characterization of scaffolds and predicting scaffold performance. It is thus anticipated that further knowledge gained from this research will allow the overall advancement of scaffolds that can be clinically used to restore large bone defects.

Antibacterial and osteogenic properties of silver-containing hydroxyapatite coatings produced using a sol gel process.

Since bacterial infection is a rising complication following the wide use of implant, there is considerable attention on the effect of implant surface properties on bacterial adhesion. In this study, the effect of silver (Ag) doped hydroxyapatite (HA) coatings on initial antibacterial adhesion and osteoblast cell proliferation and differentiation was investigated. Using a sol-gel process, HA coatings doped with 1 wt % AgNO(3) (AgHA1.0) and 1.5 wt % Ag (AgHA1.5) were prepared. Coated surfaces were characterized using X-ray diffraction (XRD) and contact angles measurements. The initial bacteria adhesion was evaluated using a RP12 strain of Staphylococcus epidermidis (ATCC 35984) and the Cowan I strain of Staphylococcus aureus, whereas osteoblast proliferation and differentiation were evaluated using human embryonic palatal mesenchyme cells (HEPM), an osteoblast precursor cell line. In this study, XRD analysis of all surfaces indicated peaks corresponding to HA. Contact angles for AgHA surfaces were observed to be significantly lower when compared to HA surfaces. In vitro initial bacterial adhesion study indicated a significantly reduced number of S. epidermidis and S. aureus on AgHA surfaces when compared to HA surface. The use of HEPM cells indicated no significant difference in double-stranded DNA (dsDNA) production between all surfaces. Additionally, no differences in alkaline phosphatase specific activity were observed between HA and AgHA1.0 surfaces. Overall, it was concluded that AgHA1.0 has the similar biological activity as HA, with respect to bone cell proliferation and differentiation. In addition, the AgHA1.0 was also concluded to have the ability to minimize the initial bacteria adhesion. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.