Objectives
The evaluation of three different drug delivery modes of bone morphogenetic protein‐2 (BMP‐2) in healing peri‐implant bone defects in beagle dogs. BMP‐2 was incorporated in or onto calcium ...phosphate (CaP) granules in various ways: (i) directly on the outer layer of granules CaP: as an adsorbed depot; (ii) during the entire precipitation process of CaP: an internally incorporated depot; or (iii) during the biomimetic coating precipitation of BMP‐2 on the surface of CaP granules: as a coating incorporated depot.
Material and Methods
After extraction of the lower molars and wound healing in 6 male beagle dogs, 36 implants were placed (n = 6 animal per group). Peri‐implant bone defects were induced. The following treatment groups were evaluated: no treatment; air abrasive surface cleaning (SC) using hydroxyapatite; SC and the subsequent filling of the defect with CaP without BMP‐2; SC plus the subsequent filling of the defect with CaP adsorbed BMP‐2; SC plus the subsequent filling of the defect with CaP internally incorporated BMP‐2; SC plus the subsequent filling of the defect with CaP coating incorporated BMP‐2. Histological and histomorphometric analyses were carried out to quantify and compare the changes in bone tissue surrounding the treated implants.
Results
In Group 1 with no treatment, four implants were lost. Group 5 with the SC and the subsequent filling of the defect with internally incorporated BMP‐2 biomimetically prepared CaP (BioCaP), whereby the BMP‐2 is incorporated in the entire volume of all BioCaP particles, showed overall the best results to regenerate bone around the implants.
Conclusion
This study concluded that the group treated with SC plus the subsequent filling of the defect with CaP BMP‐2 internally incorporated BMP‐2, whereby BMP‐2 has been incorporated in the entire volume of all CaP particles, showed overall the best results when aiming to regenerate bone around the implants.
Purpose
To repair large‐size bone defects, most bone‐defect‐filling materials in clinic need to obtain osteoinductivity either by mixing them with particulate autologous bone or adsorbing bone ...morphogenetic protein 2 (BMP2). However, both approaches encounter various limitations. In this study, we hypothesized that our novel particles of biomimetic BMP2‐coprecipitated calcium phosphate (BMP2‐cop.BioCaP) could serve as an independent and biodegradable osteoinducer to induce bone formation efficiently for these bone‐defect‐filling materials, for example, deproteinized bovine bone (DBB).
Materials and Methods
We alternately layer‐by‐layer assembled amorphous and crystalline CaP triply to enable a “bamboo‐like” growth of the particles. We functionalized BioCaP by coprecipitating BMP2 into the most outer layer of BioCaP. We monitored the degradation, osteoinductivity, and foreign‐body reaction of either BMP2‐cop.BioCaP or its combination with DBB in an ectopic site in rats.
Results
After 5 weeks, the BMP2‐cop.BioCaP significantly induced new bone formation not only alone but also when mixed with DBB. Its osteoinductive efficiency was 10‐fold higher than the adsorbed BMP2. Furthermore, BMP2‐cop.BioCaP also reduced significantly the host foreign‐body reaction to DBB in comparison with the adsorbed BMP2. After a 5‐week implantation, more than 90% of BMP2‐cop.BioCaP degraded.
Conclusions
These findings indicate a promising clinical potential for BMP2‐cop.BioCaP in the repair of large‐size bone defects.
Osteosarcoma (OS), a primary malignant bone tumor, stems from bone marrow-derived mesenchymal stem cells (BMSCs) and/or committed osteoblast precursors. Distant metastases, in particular pulmonary ...and skeletal metastases, are common in patients with OS. Moreover, extensive resection of the primary tumor and bone metastases usually leads to bone defects in these patients. Bone morphogenic protein-2 (BMP-2) has been widely applied in bone regeneration with the rationale that BMP-2 promotes osteoblastic differentiation of BMSCs. Thus, BMP-2 might be useful after OS resection to repair bone defects. However, the potential tumorigenicity of BMP-2 remains a concern that has impeded the administration of BMP-2 in patients with OS and in populations susceptible to OS with severe bone deficiency (e.g., in patients with genetic mutation diseases and aberrant activities of bone metabolism). In fact, some studies have drawn the opposite conclusion about the effect of BMP-2 on OS progression. Given the roles of BMSCs in the origination of OS and osteogenesis, we hypothesized that the responses of BMSCs to BMP-2 in the tumor milieu may be responsible for OS development. This review focuses on the relationship among BMSCs, BMP-2, and OS cells; a better understanding of this relationship may elucidate the accurate mechanisms of actions of BMP-2 in osteosarcomagenesis and thereby pave the way for clinically safer and broader administration of BMP-2 in the future. For example, a low dosage of and a slow-release delivery strategy for BMP-2 are potential topics for exploration to treat OS.
Bone grafts are in high demand due to the increase in the cases of bone defects mainly caused by trauma, old age, and disease-related bone damages. Tissue-engineered calcium phosphate (CaP) ...biomaterials match the major inorganic contents of bone, thereby could be the potential bone graft substitute. However, CaP-bone grafts lack the osteoinductivity that is vital for effective bone regeneration. In this study, we aimed to test the bone defect healing potential of biomimetically fabricated low dose BMP2-doped CaP (BMP2.BioCaP) grafts in a large animal model.
Low dose BMP2 was doped internally (BMP2-int.BioCaP) or on the surface of CaP (BMP2-sur.BioCaP) grafts during the fabrication process. Our previous study showed the robust bone regenerative potential of BMP2-int.BioCaP and BMP2-sur.BioCaP grafts in the rat ectopic model. In this study, we investigated the bone defect healing potential of BMP2.BioCaP grafts in sheep humerus/femoral defects, as well as compared with that of autologous bone graft and clinically used deproteinized bovine bone (DBB) xenograft.
Different ways of BMP2 doping did not affect the surface morphology and degradation properties of the graft materials. Micro-CT and histology results showed robustly higher bone defect-healing potential of the BMP2.BioCaP grafts compared to clinically used DBB grafts. The bone defect healing potential of BMP2.BioCaP grafts was as effective as that of the autologous bone graft. Although, BMP2-int.BioCaP doped half the amount of BMP2 compared to BMP2-sur.BioCaP, its' bone defect healing potential was even robust. The BMP2.BioCaP grafts showed less immunogenicity compared to BioCaP or DBB grafts. The volume density of blood vessel-like and bone marrow-like structures in both BMP2.BioCaP graft groups were in a similar extent to the autologous group. Meticulous observation of higher magnification histological images showed active bone regeneration and remodeling during bone defect healing in BMP2.BioCaP graft groups.
The robust bone regenerative potential of BMP2.BioCaP grafts in the ectopic model and
bone defects in small and large animals warrant the pre-clinical studies on large animal critical-sized segmental bone defects.
Objectives: To investigate the influence of protein incorporation on the resistance of biomimetic calcium‐phosphate coatings to the shear forces that are generated during implant insertion.
Materials ...and Methods: Thirty‐eight standard (5 × 13 mm) Osseotite® implants were coated biomimetically with a layer of calcium phosphate, which either lacked or bore a co‐precipitated (incorporated) depot of the model protein bovine serum albumin (BSA). The coated implants were inserted into either artificial bone (n=18) or the explanted mandibles of adult pigs (n=12). The former set‐up was established for the measurement of torque and of coating losses during the insertion process. The latter set‐up was established for the histological and histomorphometric analysis of the fate of the coatings after implantation.
Results: BSA‐bearing coatings had higher mean torque values than did those that bore no protein depot. During the insertion process, less material was lost from the former than from the latter type of coating. The histological and histomorphometric analysis revealed fragments of material to be sheared off from both types of coating at vulnerable points, namely, at the tips of the threads. The sheared‐off fragments were retained within the peri‐implant space.
Conclusion: The incorporation of a protein into a biomimetically prepared calcium‐phosphate coating increases its resistance to the shear forces that are generated during implant insertion. In a clinical setting, the incorporated protein would be an osteogenic agent, whose osteoinductive potential would not be compromised by the shearing off of coating material, and the osteoconductivity of an exposed implant surface would not be less than that of a coated one.
To cite this article:
Hägi TT, Enggist L, Michel D, Ferguson SJ, Liu Y, Hunziker EB. Mechanical insertion properties of calcium‐phosphate implant coatings. Clin. Oral Impl. Res. 21, 2010; 1214–1222. doi: 10.1111/j.1600‐0501.2010.01916.x
Abstract The flexible alloplastic materials that are used in bone-reconstruction surgery lack the mechanical stability that is necessary for sustained bone formation, even if this process is promoted ...by the application of an osteogenic agent, such as BMP-2. We hypothesize that if BMP-2 is delivered gradually, in a cell-mediated manner, to the surgical site, then the scaffolding material's lack of mechanical stability becomes a matter of indifference. Flexible discs of Ethisorb™ were functionalized with BMP-2, which was either adsorbed directly onto the material (rapid release kinetics) or incorporated into a calcium-phosphate coating (slow release kinetics). Unstabilized and titanium-plate-stabilized samples were implanted subcutaneously in rats and retrieved up to 14 days later for a histomorphometric analysis of bone and cartilage volumes. On day 14, the bone volume associated with titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2 was 10-fold higher than that associated with their mechanically unstabilized counterparts. The bone volume associated with discs bearing a coating-incorporated depot of BMP-2 was similar in the mechanically unstabilized and titanium-plate-stabilized groups, and comparable to that associated with the titanium-plate-stabilized discs bearing an adsorbed depot of BMP-2. Hence, if an osteogenic agent is delivered in a cell-mediated manner (via coating degradation), ossification can be promoted even within a mechanically unstable environment.
Recently, stainless steel (SSL) miniscrew implants have been used in orthodontic clinics as temporary anchorage devices. Although they have excellent physical properties, their biocompatibility is ...relatively poor. Previously, our group developed a two-phase biomimetic calcium phosphate (BioCaP) coating that can significantly improve the biocompatibility of medical devices. This study aimed to improve the biocompatibility of SSL by coating SSL surface with the BioCaP coating.
Titanium (Ti) discs and SSL discs (diameter: 5 mm, thickness: 1 mm) were used in this study. To form an amorphous layer, the Ti discs were immersed in a biomimetic modified Tyrode solution (BMT) for 24 h. The SSL discs were immersed in the same solution for 0 h, 12 h, 24 h, 36 h and 48 h. To form a crystalline layer, the discs were then immersed in a supersaturated calcium phosphate solution (CPS) for 48 h. The surface properties of the BioCaP coatings were analysed. In addition, bovine serum albumin (BSA) was incorporated into the crystalline layer during biomimetic mineralisation as a model protein.
The morphology, chemical composition and drug loading capacity of the BioCaP coating on smooth SSL were confirmed. This coating improved roughness and wettability of SSL surface. In vitro, with the extension of BMT coating period, the cell seeding efficiency, cell spreading area and cell proliferation on the BioCaP coating were increased.
These in vitro results show that the BioCaP coating can improve surface properties of smooth medical grade SSL and serve as a carrier system for bioactive agents.
Sims (passion fruit) is an economically important fruit crop. However, a new flower dry rot has occurred in orchards located in Zhanjiang, China, and has led to serious production loss. Its disease ...incidence is approximately 30 to 40%. A total of 221 isolates of
sp. were obtained from samples of three types of symptomatic flowers. Three representative single-spore isolates (PaB-1, PaB-2, and PaB-3) from each type were used for pathogenicity tests, multilocus phylogenetic analyses, and morphological descriptions. Pathogenicity tests of buds of 5-month-old
plants showed symptoms similar to those observed in nature, and Koch's postulates were achieved. By comparing 36 typical species from the
-ID database, multilocus phylogenetic analyses showed that the sequences of
,
, and ITS of these isolates belong to the
clade of the
species complex (FIESC-17-a) with an independent branch. Therefore, the pathogenic isolates were identified as
(FIESC-17-a). Moreover, in this study, the conidial anastomosis tubes were first observed in the FIESC. This is the first report of flower dry rot on
caused by
. Further studies should be performed to determine effective disease management strategies.
Aim
To evaluate the effect of bone morphogenetic protein 2 (BMP‐2) incorporated biomimetic calcium phosphate (BMP‐2/BioCaP) in conjunction with barrier membrane on periodontal regeneration in chronic ...periodontitis experimental model.
Material and Methods
Chronic periodontitis experimental model with critical‐sized supra‐alveolar defects was created in 15 dogs’ mandibles. After the initial periodontal therapy, the defects were randomly assigned to the following groups: (a) control; (b) barrier membrane; (c) deproteinized bovine bone mineral + barrier membrane; (d) BioCaP + barrier membrane and (e) BMP‐2/BioCaP + barrier membrane (6 quadrants with 18 teeth per group). Eight weeks later, clinical examinations, micro‐CT, and histomorphometric analyses were performed.
Results
Clinical examinations, including plaque index, bleeding index, and probing depth, were similar for all groups. In contrast, the clinical attachment loss was significantly lower in defects grafted with BMP‐2/BioCaP and barrier membrane. The micro‐CT results showed that the height of mineralized tissue in defects grafted with BMP‐2/BioCaP and barrier membrane was significantly higher. For histometric analysis, the defects grafted with BMP‐2/BioCaP and barrier membrane exhibited significantly more connective tissue height, new cementum height, new bone height and area, as well as less down‐growth of junctional epithelium.
Conclusion
BMP‐2/BioCaP could be a promising bone substitute for periodontal regeneration.
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