Co-delivery of platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) coated onto heparinized titanium for improving osteoblast function and osteointegration

Abstract

The aim of this study was to improve osteoblast function by delivering two growth factors, PDGF-BB and BMP-2, incorporated onto heparinized titanium (Hep-Ti) substrate. To achieve co-delivery of PDGF-BB and BMP-2, the surface of anodized Ti was immobilized with heparin, and then the two growth factors were coated onto the Hep-Ti surface. Incorporation of the two growth factors onto Hep-Ti was evaluated by SEM and XPS. Incorporated PDGF-BB and BMP-2 were released from the Hep-Ti substrate in a sustained manner. In vitro studies revealed that osteoblasts grown on PDGF-BB- and BMP-2-immobilized Hep-Ti increased ALP activity, calcium deposition, osteocalcin and osteopontin levels as compared to those grown on PDGF-BB alone- or BMP-2 alone-immobilized Hep-Ti. These results suggested that co-delivery of PDGF-BB and BMP-2 using Hep-Ti substrate will be a promising material for the enhancement of osteoblast function and osteointegration.

Effects of Immobilizations of rhBMP-2 and/or rhPDGF-BB on Titanium Implant Surfaces on Osseointegration and Bone Regeneration

“…ALP activities of cells that are cultured on PDGF-BB and/or BMP/Hepa/Ti were found to be significantly higher than those of cells cultured on untreated Ti on days 7 and 10 (* p < 0.05 and ** p < 0.01). As reported in a previous study [6,56], our finding confirmed that rhBMP-2 and rhPDGF-BB both stimulate osteoblast differentiation. Furthermore, the calcium contents of cells cultured on PDGF-BB or/and BMP/Hepa/Ti were significantly higher than those of cells cultured on untreated Ti on days 7 and 21 (* p < 0.05 and ** p < 0.01).…”

“…In the result of previous cell studies [6], PDGF-BB (5 ng/mL)/BMP-2(50 ng/mL)/Hepa/Ti (a 1:10 ratio of growth factors) was significantly higher than BMP/Hepa/Ti, whereas in this study, PDGF-BB (50 ng/mL)/BMP-2 (50 ng/mL)/Hepa/Ti (a 1:1 ratio) was significantly lower than BMP/Hepa/Ti. Furthermore, ALP, calcium deposition, and gene expression not synergistically increased by the copresence of rhPDGF-BB and rhBMP-2.…”

“…In PDGF, the previous study of Choo et al [33] reported that the appropriate concentration of PDGF was from 0.3 mg/mL up to 1 mg/mL, thus we chose 0.75 mg/mL of PDGF concentration within that range. BMP and PDGF combined groups were studied in 1:10 ratio (PDGF:BMP) in previous cell study [6], but we intended to increase the rate of PDGF to get enhanced bone regeneration as ratio of 1:1. The results of our in vitro release experiments indicated that the inclusion of heparin achieved sustained growth factor release, although previous studies have reported a burst release pattern resulting in the release of 70%-90% over the first 6 h [52].…”

“…To improve the success rate of these patients, it is important to increase the initial fixation of implant fixtures and to shorten the time required for the upper prosthesis to connect [3]. Recently, developments have focused on biomimetic treatment techniques based on applying biomolecules, such as bone morphogenetic protein (BMP) or platelet-derived growth factor (PDGF), to implant surfaces to address these problems [4][5][6].…”

Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis

“…47 The ALP activity increased gradually in a time-dependent manner ( Figure 7). Although the ALP activity of the blank nanocomplex group was significantly lower than that of the others, there were no significant differences among the three GF-loaded nanocomplex groups on day 7.…”