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Injectable hybrid system for strontium local delivery promotes bone regeneration in a rat critical-sized defect model.

ABSTRACT: Strontium (Sr) has been described as having beneficial influence in bone strength and architecture. However, negative systemic effects have been reported on oral administration of Sr ranelate, leading to strict restrictions in clinical application. We hypothesized that local delivery of Sr improves osteogenesis without eliciting detrimental side effects. Therefore, the in vivo response to an injectable Sr-hybrid system composed of RGD-alginate hydrogel cross-linked in situ with Sr and reinforced with Sr-doped hydroxyapatite microspheres, was investigated. The system was injected in a critical-sized bone defect model and compared to a similar Sr-free material. Micro-CT results show a trend towards higher new bone formed in Sr-hybrid group and major histological differences were observed between groups. Higher cell invasion was detected at the center of the defect of Sr-hybrid group after 15 days with earlier bone formation. Higher material degradation with increase of collagen fibers and bone formation in the center of the defect after 60 days was observed as opposed to bone formation restricted to the periphery of the defect in the control. These histological findings support the evidence of an improved response with the Sr enriched material. Importantly, no alterations were observed in the Sr levels in systemic organs or serum.

SUBMITTER: Henriques Lourenco A

PROVIDER: S-EPMC5506032 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Injectable hybrid system for strontium local delivery promotes bone regeneration in a rat critical-sized defect model.

Henriques Lourenço Ana A Neves Nuno N Ribeiro-Machado Cláudia C Sousa Susana R SR Lamghari Meriem M Barrias Cristina C CC Trigo Cabral Abel A Barbosa Mário A MA Ribeiro Cristina C CC

Scientific reports 20170711 1

Strontium (Sr) has been described as having beneficial influence in bone strength and architecture. However, negative systemic effects have been reported on oral administration of Sr ranelate, leading to strict restrictions in clinical application. We hypothesized that local delivery of Sr improves osteogenesis without eliciting detrimental side effects. Therefore, the in vivo response to an injectable Sr-hybrid system composed of RGD-alginate hydrogel cross-linked in situ with Sr and reinforced ...[more]

PMID: 28698571

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Project description:BackgroundRepair of large-sized bone defects is a challengeable obstacle in orthopedics and evoked the demand for the development of biomaterials that could induce bone repair in such defects. Recently, UiO-66 has emerged as an attractive metal-organic framework (MOF) nanostructure that is incorporated in biomedical applications due to its biocompatibility, porosity, and stability. In addition, its osteogenic properties have earned a great interest as a promising field of research. Thus, the UiO-66 was prepared in this study and assessed for its potential to stimulate and support osteogenesis in vitro and in vivo in a rabbit femoral condyle defect model. The nanomaterial was fabricated and characterized using x-ray diffraction (XRD) and transmission electron microscopy (TEM). Afterward, in vitro cytotoxicity and hemolysis assays were performed to investigate UiO-66 biocompatibility. Furthermore, the material in vitro capability to upregulate osteoblast marker genes was assessed using qPCR. Next, the in vivo new bone formation potential of the UiO-66 nanomaterial was evaluated after induction of bone defects in rabbit femoral condyles. These defects were left empty or filled with UiO-66 nanomaterial and monitored at weeks 4, 8, and 12 after bone defect induction using x-ray, computed tomography (CT), histological examinations, and qPCR analysis of osteocalcin (OC) and osteopontin (OP) expressions.ResultsThe designed UiO-66 nanomaterial showed excellent cytocompatibility and hemocompatibility and stimulated the in vitro osteoblast functions. The in vivo osteogenesis was enhanced in the UiO-66 treated group compared to the control group, whereas evidence of healing of the treated bone defects was observed grossly and histologically. Interestingly, UiO-66 implanted defects displayed a significant osteoid tissue and collagen deposition compared to control defects. Moreover, the UiO-66 nanomaterial demonstrated the potential to upregulate OC and OP in vivo.ConclusionsThe UiO-66 nanomaterial implantation possesses a stimulatory impact on the healing process of critical-sized bone defects indicating that UiO-66 is a promising biomaterial for application in bone tissue engineering.

Project description:BackgroundThe osteogenic capabilities and biodegradability of octacalcium phosphate (OCP) composites make them unique. Despite the excellent characteristics of OCP, their use is limited due to handling difficulties. In this study, we aimed to evaluate and compare three types of OCPs (cemented OCP (C-OCP), C-OCP with collagen (OCP/Col), and synthetic OCP (S-OCP) with alginate (OCP/Alg)) versus commercially available β-tricalcium phosphate (β-TCP) regarding their potential to accelerate bone formation in defective rat tibias.MethodsThe specimens with OCP composite were manufactured into 5 mm cubes and inserted into the segmental defects of rat tibias fixed with an external fixator. In addition, 3 mm-hole defects in rat tibias were evaluated to compare the graft material properties in different clinical situations. Serial X-ray studies were evaluated weekly and the tibias were harvested at postoperative 6 weeks or 8 weeks for radiologic evaluation. Histological and histomorphometric analyses were performed to evaluate the acceleration of bone formation.ResultsIn the critical-defect model, OCP/Alg showed bone bridges between segmentally resected bone ends that were comparable to those of β-TCP. However, differences were observed in the residual graft materials. Most β-TCP was maintained until 8 weeks postoperatively; however, OCP/Alg was more biodegradable. In addition calcification in the β-TCP occurred at the directly contacted area between graft particles and bony ingrowth was observed in the region adjacent resected surface of tibia. In contrast, no direct bony ingrowth was observed in OCP-based materials, but osteogenesis induced from resected surface of tibia was more active. In the hole-defect model, OCP/Col accelerated bone formation. β-TCP and OCP/Alg showed similar patterns with relatively higher biodegradability. In histology, among the OCP-based materials, directly contacted new bone was formed only in OCP/Alg group. The new bone formation in the periphery area of graft materials was much more active in the OCP-based materials, and the newly formed bone showed a thicker trabecular and more mature appearance than the β-TCP group.ConclusionsIn this study, OCP/Alg was equivalent to β-TCP in the acceleration of bone formation with better biodegradability appropriate for clinical situations in different circumstances. Our OCP/Col composite showed fast degradation, which makes it unsuitable for use in mechanical stress conditions in clinical orthopedic settings.The translational potential of this articleIn our research, we compared our various manufactured OCP composites to commercially available β-TCP in critical-defect rat tibia model. OCP/Col showed acceleration in hole-defect model as previous studies in dental field but in our critical-sized defect model it resorbed fast without acceleration of bony union. OCP/Alg showed matched results compared to β-TCP and relatively fast resorption so we showed market value in special clinical indication depending on treatment strategy. This is the first OCP composite study in orthopaedics with animal critical-sized tibia bone study and further study should be considered for clinical application based on this study.

Project description:PurposePluripotent cells residing in the periosteum, a bi-layered membrane enveloping all bones, exhibit a remarkable regenerative capacity to fill in critical sized defects of the ovine femur within two weeks of treatment. Harnessing the regenerative power of the periosteum appears to be limited only by the amount of healthy periosteum available. Here we use a substitute periosteum, a delivery device cum implant, to test the hypothesis that directional delivery of endogenous periosteal factors enhances bone defect healing.MethodsNewly adapted surgical protocols were used to create critical sized, middiaphyseal femur defects in four groups of five skeletally mature Swiss alpine sheep. Each group was treated using a periosteum substitute for the controlled addition of periosteal factors including the presence of collagen in the periosteum (Group 1), periosteum derived cells (Group 2), and autogenic periosteal strips (Group 3). Control group animals were treated with an isotropic elastomer membrane alone. We hypothesized that periosteal substitute membranes incorporating the most periosteal factors would show superior defect infilling compared to substitute membranes integrating fewer factors (i.e. Group 3>Group 2>Group 1>Control).ResultsBased on micro-computed tomography data, bone defects enveloped by substitute periosteum enabling directional delivery of periosteal factors exhibit superior bony bridging compared to those sheathed with isotropic membrane controls (Group 3>Group 2>Group 1, Control). Quantitative histological analysis shows significantly increased de novo tissue generation with delivery of periosteal factors, compared to the substitute periosteum containing a collagen membrane alone (Group 1) as well as compared to the isotropic control membrane. Greatest tissue generation and maximal defect bridging was observed when autologous periosteal transplant strips were included in the periosteum substitute.ConclusionPeriosteum-derived cells as well as other factors intrinsic to periosteum play a key role for infilling of critical sized defects.

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Injectable hybrid system for strontium local delivery promotes bone regeneration in a rat critical-sized defect model.

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Injectable hybrid system for strontium local delivery promotes bone regeneration in a rat critical-sized defect model.

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