Bone regeneration in ceramic scaffolds with variable concentrations of PDRN and rhBMP-2

This study evaluated the bone regeneration capacity and mechanical properties of block-type hydroxyapatite (HA)/tricalcium phosphate (TCP) scaffolds in response to different concentrations of polydeoxyribonucleotide (PDRN) and recombinant human bone morphogenic protein 2 (rhBMP-2). Thirty-two male white rabbits were used as a model of calvarial bone defect and classified into eight groups according to type and concentration of growth factor administered, viz., control group (only HA/TCP scaffold), scaffold + PDRN (0.1, 1, 5, and 10 mg/mL each) and scaffold + rhBMP-2 (0.01, 0.05, and 0.1 mg/mL each). The specimens were evaluated using histomorphometric and radiological analyses. Histomorphometric analyses indicated that the administration of PDRN did not increase bone formation. However, significant increases in bone formation were observed with the administration of rhBMP-2 at 0.05 and 0.10 mg/mL on week 8 compared to the control (p < 0.05). Radiological analyses revealed a significant increase in bone formation at week 8 with the administration of PDRN at 5 mg/mL and 10 mg/mL, and rhBMP-2 at 0.05 or 0.10 mg/mL compared to the control (p < 0.05). Our findings show that block-type HA/TCP scaffolds possess sufficient mechanical strength and bone regeneration capacity when used with optimal concentrations of growth factors.

Development of cyclic peptides with potent in vivo osteogenic activity through RaPID-based affinity maturation

Osteoporosis is caused by a disequilibrium between bone resorption and bone formation. Therapeutics for osteoporosis can be divided into antiresorptives that suppress bone resorption and anabolics which increase bone formation. Currently, the only anabolic treatment options are parathyroid hormone mimetics or an anti-sclerostin monoclonal antibody. With the current global increases in demographics at risk for osteoporosis, development of therapeutics that elicit anabolic activity through alternative mechanisms is imperative. Blockade of the PlexinB1 and Semaphorin4D interaction on osteoblasts has been shown to be a promising mechanism to increase bone formation. Here we report the discovery of cyclic peptides by a novel RaPID (Random nonstandard Peptides Integrated Discovery) system-based affinity maturation methodology that generated the peptide PB1m6A9 which binds with high affinity to both human and mouse PlexinB1. The chemically dimerized peptide, PB1d6A9, showed potent inhibition of PlexinB1 signaling in mouse primary osteoblast cultures, resulting in significant enhancement of bone formation even compared to non-Semaphorin4D–treated controls. This high anabolic activity was also observed in vivo when the lipidated PB1d6A9 (PB1d6A9-Pal) was intravenously administered once weekly to ovariectomized mice, leading to complete rescue of bone loss. The potent osteogenic properties of this peptide shows great promise as an addition to the current anabolic treatment options for bone diseases such as osteoporosis.

Combination Use of BMP2 and VEGF165 Promotes Osseointegration and Stability of Titanium Implants in Irradiated Bone

Background. Clinical data demonstrated that failure rate of titanium implant in irradiated bone was 2-3 times higher than that in nonirradiated bone and it is difficult to get the ideal results in irradiated bone. Purpose. The aim of the study was to investigate the effects of HBO, BMP2, VEGF165, and combined use of BMP2/VEGF165 on osseointegration and stability of titanium implant in irradiated bone. Materials and Methods. Sixty rabbits were randomly assigned to 5 groups (control group, HBO group, VEGF165 group, BMP2 group, and BMP2/VEGF165 group) after receiving 15 Gy radiation. Implant surgery was performed on tibias eight weeks later. They were sacrificed at two or eight weeks after operation. Implant stability, calcium, and ALP activity in serum, the ratio of bone volume to total volume, the rate of bone growth, and gene expression were assessed. Result. There was no mortality and no implants failed during the experiment. Implant stability was significantly compromised in the control group compared to the other four experimental groups, and the BMP2/VEGF165 group had the highest implant stability. HBO, BMP2, and VEGF165 significantly increased BV/TV and the rate of bone growth, while the BMP2/VEGF165 showed the best effect among groups. The expression of RUNX2 in HBO, BMP2, and VEGF165/BMP2 group was higher than that in the VEGF165 and control groups at two weeks. The expression of OCN in HBO, BMP2, VEGF165, and VEGF165/BMP2 groups was higher than that in the control group, and the gene expression of CD31 was higher in HBO, VEGF165, and BMP2/VEGF165 groups than that in control and BMP2 groups. Conclusion. HBO, BMP2, and VEGF165 could increase bone formation around the implant and improved the implant stability in irradiated bone. The combination use of BMP2 and VEGF165 may be promising in the treatment of implant patients with radiotherapy.

The effect of local delivery of adiponectin from biodegradable microsphere–scaffold composites on new bone formation in adiponectin knockout mice

Adiponectin (APN) is the most abundant adipocyte-secreted adipokine; it increase bone formation partially by promoting osteoblast proliferationviathe APPL1/PI3K pathway.