Papers by Keyword: BMP-2

Abstract: Aim: This study was performed to evaluate histologically and radiographically the quality and the quantity of the formed bone after alveolar ridge augmentation using micro-granules of SCPC50 resorbable bioactive ceramic with and without rhBMP-2.Material and methods: Saddle-type alveolar ridge defects (12X7) mm were created in dog mandibles. Defects were grafted with micro-granules of SCPC50 resorbable bioactive ceramic loaded with rhBMP-2 10 μg and covered with collagen membrane. Control groups included defects grafted with SCPC50 granules without rhBMP-2 and un-grafted defects. Radiographs were taken for the dissected defect sites at 2 and 4 months. Radiographs were analyzed for bone density using the ImageJ 1.46 program. Dissected defect sites were then fixed in formalin and processed for histologic and hitomorphometric analysis. Data was statistically analyzed using student t-test and 1-way ANOVA test with p<0.05 as statistically significant.Results: Radiographic analysis of augmented bone revealed bone density equal to or denser than the surrounding native bone in SCPC50 treated defects with and without rhBMP-2. Qualitative and quantitative histologic evaluation revealed dense well arranged bone trabeculae in both the SCPC50 treated defects with and without rhBMP-2 with more rapid bone formation and graft resorption in the rhBMP-2 group. Maturation of newly formed bone was noted on the periphery and inside the SCPC50 pores. No adverse reactions, excessive bone formation or fluid filled voids were detected.Conclusion: Results of this study suggest that SCPC50 is an effective graft material in alveolar ridge augmentation. SCPC/rhBMP-2 hybrid accelerated bone regeneration and enhanced bone quality and quantity as revealed by radiographic and histologic evaluation.

Abstract: Objective: To functionalize the Bio-Oss^® Block with biomimetic coating incorporating BMP2 and evaluate the release kinetics of the incorporated BMP2 In Vitro.Materials and methods: Bio-Oss^® Blocks were prepared with the size of 7mm x 10mm x 4mm. Each block was immersed and suspended in 300ml 5-fold-concentrated modified Tyrode solution for 24 hours to form a seeding substratum. BMP2 at the concentration of 10ug/ml was added into 120ml supersaturated calcium phosphate solution and co-precipitated within the growing layer for 48 hours. The loading amount of incorporated BMP2 was determined using enzyme-linked immunosorbent assay . The surface characterization of the coating was evaluated by scanning electron microscopy. The distribution of coating-incorporated protein was mapped by a confocal laser-scanning microscope. BMP2 release profiles from the functionalized blocks under different circumstances were monitored. Results: The total loading of BMP2 in a BMP2-incorporated-block is 50.35 ± 6.41μg. The crystalline coating layer deposited on both the superficial surfaces and internal surfaces of the blocks. The BMP2 was distributed homogeneously in the whole block. The coating-incorporated depot of BMP2 barely released in Tris-HCl buffered solution (pH of 7.4). However, when the functionalized blocks were immersed in Citric acid-Sodium citrate buffered solution (pH of 5), or were co-cultured with osteoclasts, the coating-incorporated BMP2 depot showed a sustained release.Conclusions: BMP2 were successfully incorporated onto and into the Bio-Oss^® Blocks. A sustained delivery of a lower concentration of BMP2 (μg-BMP2) from Bio-Oss^® Block was achieved in acidic solution or with the mediation of osteoclasts.

Abstract: The bone substation grafts, such as hydroxyapatite, TCP, have been used in the clinical. But it is found that they are not capable of enhancing bone regeneration due to their poor osteoinductive compared with allograft and autograft. In order to increase the osteoinductive, bone morphogenetic protein 2 (BMP-2) has highlighted to incorporate into a three dimensional reservoir. The purpose of the present study was to develop a novel drug delivery system with the capability of controlled releasing BMP-2. In this study, BMP-2/Chitosan (CS) microspheres were succeeded loaded on the deproteinized bovine bone (DBB) scaffold. The release profile of BMP-2 study indicated an initial burst release followed by a sustained release. In vitro bioactivity assay revealed that the encapsulated growth factor was biologically active as evidenced by cell culture. Therefore, the novel strategy of this microspheres-scaffold system is potentially to utilize the bone tissue engineered.

Abstract: The interaction between protein molecules and the hydroxyapatite (HAP) nano surface is an important research topic in many fields. However, the nature of their non-covalent bonding is still not clear at the atomic level. In this work, molecular dynamics (MD) simulation and steered molecular dynamics (SMD) simulation were used to study the adsorption-desorption dynamics of BMP-2 on HAP nano surface. The results suggest that there are two types of adsorption functional groups, –OH and –COO–. And the –COO– group plays the key role. Correspondingly, the Coulombic force between –COO– (in protein BMP-2) and Ca2+ (in the HAP nano particles) is the main adsorption mechanism. As to the conversation for protein BMP-2, it is found that the specific adsorption-desorption behaviors of BMP-2 play a great role in the conversation of the protein. And the conservation may go worse in the regions where the adsorbed residues are located.

Abstract: Body fluid permeability and blood compatibility of biomaterials are especially critical properties for regenerative bone therapy [1, 2]. To have a role in bone repair, biomaterials must have the adsorptive performance of various bone growth factors. The bone-inductive property of rabbit dentin was discovered in 1967 [3]. In our previous study, we have been researching the autograft of human demineralized dentin matrices (DDM) as a clinical study [4]. DDM is an acid-insoluble collagenous material. On the other hand, hydroxyapatite (HAp) is a mineralized material. Commercially available HAp block (APACERAM-AX^®, 85%-porosity with micropore) has been used as the artificial biomaterial in bone therapy [5]. Bone morphogenetic proteins (BMPs) are the strong hard tissue-inducing factors [6]. In this study, we investigated the existence of BMP-2 and -7, among proteins adsorbed to DDM and HAp, using immunoblottong analyses. The DDM granules and HAp blocks (64mm³) were implanted subcutaneously in 8-week-old Wistar rats, and sacrificed at 2 days after the implantation. Explanted DDM and HAp were homogenized by the ultrasonic procedure in phosphate-buffered saline (PBS) and the adsorbed proteins were separated on a 5-20% sodium dodecyl sulphate (SDS) polyacrylamide gradient gel by electrophoresis. For Western blotting, proteins in the gel were transferred to a polyvinylidene difluoride membrane and detected by anti-BMP-2 monoclonal antibody and anti-BMP-7 monoclonal antibody. BMP-2 and BMP-7 were detected as a major band at 50 kDa among proteins collected from the in vivo implanted DDM and HAp. BMP-2 was detected the second major band at 125 kDa in HAp and both BMP-2 and BMP-7 were detected the some minor bands in DDM and HAp. The bands of BMP-2 were stronger than those of BMP-7 in all. The DDM and HAp adsorbed BMP-2 and BMP-7. These results indicate that DDM is a useful bone substitute as much as HAp, adsorbed to the bone-inducing factors, in the bone engineering field.

Abstract: Bone Morphogenetic Protein 2 (BMP-2) is a member of the transforming growth factor superfamily. It plays an important role in stimulating osteoblast differentiation and bone formation, and has been widely utilized in clinical bone repairing by implantation. In this study, the nano-hydroxyapatite (nHA)/silk fibroin (SF) porous scaffolds were fabricated for the sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2), and then used to address the hypothesis that rhBMP-2 delivered from the scaffolds could enhance the bone formation in vitro. We optimized an effective method using a prokaryotic expression system to produce rhBMP-2. The rhBMP-2 was expressed, purified and renatured in vitro. And then the rhBMP-2 was loaded onto the nHA/SF scaffolds. The bioactivities of rhBMP-2-loaded nHA/SF scaffolds were assessed in vitro. The results showed that the rhBMP-2 promoted the osteoblasts adhesion and proliferation on the nHA/SF scaffolds. Also, the rhBMP-2 released from the nHA/SF scaffold stimulated a significant increase in alkaline phosphatase (ALP) activity of osteoblasts in vitro. These results demonstrated that the rhBMP-2-loaded nHA/SF scaffolds could promote the bone regeneration and showed potential applications in the bone tissue engineering.

Abstract: The aim of this study is to investigate in vivo local BMP-2 PK and bone induction in two bioceramics blocks (HAp, β-TCP), based on different composition and surface structures. We estimated the in vivo release profile of 125I–labeled BMP-2 and bone induction of hard tissues histologically. β-TCP is more effective for both BMP-2 retention and bone induction, compared to HAp, in the ectopic model.

Abstract: The present study was designed to investigate whether bone morphogenetic protein-2 (BMP-2) adsorbed onto octacalcium phosphate (OCP) and hydroxyapatite (HA) surfaces influences osteoblastic cell differentiation. Osteoblastic cell line, UAMS32, were cultured on plastic plate that was coated of synthetic OCP and HA. BMP-2 was pre-adsorbed on these calcium phosphates at 4°C or room temperature for 24h. The cells more proliferated on the BMP-2 pre-adsorbed OCP and HA than that of the controls (OCP and HA coating without BMP-2). ALP activities were higher on HA than on OCP when BMP-2 were pre-adsorbed at 4°C than at room temperature. The results suggest that pre-adsorption of BMP-2 in different temperature affects osteoblastic cell differentiation, most probably through different adsorption state of BMP-2 on this calcium phosphate.

Abstract: Hydroxyapatite (HAp) has been used as a biomaterial for hard tissues. Critical characteristics of biomaterials will include surface geometry, hydrophobicity and hydrophilicity, crystallinity, biodegradation rates, and release pharmacokinetics (PK) of incorporated molecules such as BMP-2. Optimizing BMP-2 for clinical application may be dependent on localized sustained release from biomaterials. We forcused on in vivo local BMP-2 PK and bone induction in two ceramics systems, based on different surface structures. The functionally graded apatites (fg-HAp) was designed by the step-wise calcinations and partial dissolution-precipitation methods. We estimated the in vivo release profile of 125I-labeled BMP-2 from fg-HAp and the dose response of bone induction by BMP-2 in the back subcutis histologically. Bulk-HAp (b-HAp) by only the step-wise calcinations was prepared as a control. The amount of BMP-2 remaining in the fg-HAp at 1 day after implantation was 83.8%, while that was 34.6% in the b-HAp. Moreover, ectopic bone formation were found surely in the fg-HAp/BMP-2 (0.5μg) system at 3 weeks, not in the b-HAp/BMP-2 system. By using fg-HAp, it is likely that an extremely low dose of BMP-2 is enough to enhance bone induction if BMP-2 is appropriately delivered to the site of action.