Femur window—a new approach to microcirculation of living bone in situ

Hansen-Algenstaedt, Nils; Schaefer, Christian; Wolfram, Lars; Joscheck, Claudia; Schroeder, Malte; Algenstaedt, Petra; Rüther, W.

doi:10.1016/j.orthres.2005.02.013

Cited by 32 publications

(37 citation statements)

References 50 publications

(51 reference statements)

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“…Since for the intended orthopaedic application small arteries and capillaries with a blood flow velocity of 1 mm/s [25] as well as neovascularization are the main issues of interest, the standard flow velocity of the current in vitro experimental setup was chosen to be 1 mm/s. Principally, the blood flow velocity within the bone is markedly slower than in the adjacent tissue [26,27]. Furthermore, enhanced blood supply in the injured area via e.g.…”

Section: Discussionmentioning

confidence: 99%

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Angrisani

Foth

Kietzmann

et al. 2013

Journal of Nanobiotechnology

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BackgroundIn orthopaedic surgery, accumulation of agents such as anti-infectives in the bone as target tissue is difficult. The use of magnetic nanoparticles (MNPs) as carriers principally enables their accumulation via an externally applied magnetic field. Magnetizable implants are principally able to increase the strength of an externally applied magnetic field to reach also deep-seated parts in the body. Therefore, the integration of bone-addressed therapeutics in MNPs and their accumulation at a magnetic orthopaedic implant could improve the treatment of implant related infections. In this study a martensitic steel platelet as implant placeholder was used to examine its accumulation and retention capacity of MNPs in an in vitro experimental set up considering different experimental frame conditions as magnet quantity and distance to each other, implant thickness and flow velocity.ResultsThe magnetic field strength increased to approximately 112% when a martensitic stainless steel platelet was located between the magnet poles. Therewith a significantly higher amount of magnetic nanoparticles could be accumulated in the area of the platelet compared to the sole magnetic field. During flushing of the tube system mimicking the in vivo blood flow, the magnetized platelet was able to retain a higher amount of MNPs without an external magnetic field compared to the set up with no mounted platelet during flushing of the system. Generally, a higher flow velocity led to lower amounts of accumulated MNPs. A higher quantity of magnets and a lower distance between magnets led to a higher magnetic field strength. Albeit not significantly the magnetic field strength tended to increase with thicker platelets.ConclusionA martensitic steel platelet significantly improved the attachment of magnetic nanoparticles in an in vitro flow system and therewith indicates the potential of magnetic implant materials in orthopaedic surgery. The use of a remanent magnetic implant material could improve the efficiency of capturing MNPs especially when the external magnetic field is turned off thus facilitating and prolonging the effect. In this way higher drug levels in the target area might be attained resulting in lower inconveniences for the patient.

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Section: Discussionmentioning

confidence: 99%

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Angrisani

Foth

Kietzmann

et al. 2013

Journal of Nanobiotechnology

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“…Prior to surgical procedures mice were anesthetized (7.5 mg ketamine hydrochloride and 2.5 mg xylazine/100 g body weight), the skin was shaved and depilated. For noninvasive and continuous intravital microscopy a “femur window” (Machine Shop, University Hamburg, Germany) was implanted to the right femur diaphysis as described more detailed previously 18. Prior to femur window fixation and wound closure, a suspension of 1 × 10 6 pDsRed‐MCF‐7 cells in 4 µl of nutrition media was implanted into the cancellous bone of the diaphysis.…”

Section: Methodsmentioning

confidence: 99%

“…However, little is known about the microcirculation of bone metastases compared to soft tissue tumors despite the importance of local tumor–host interactions 15–17. We recently published a bone tumor model, which allows continuous observation of microvascular properties in vivo, and described morphological angiogenic alterations during tumor growth 16, 18. Since functional properties of tumor microcirculation greatly contribute to tumor perfusion and drug delivery,12, 13 the objective of the present study was to characterize angiogenesis and tumor perfusion of experimental bone tumors.…”

mentioning

confidence: 99%

Microcirculation of secondary bone tumors in vivo: The impact of minor surgery at a distal site

Schaefer

Fuhrhop

Schroeder

et al. 2010

Journal Orthopaedic Research

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Microcirculatory properties of tumors play a pivotal role in tumor progression and inefficacy of therapies. It has been hypothesized that surgical interventions result in an accelerated tumor growth by increasing the level of pro-angiogenic cytokines with subsequent amplification of tumor angiogenesis. To characterize the microvascular properties of secondary bone tumors in vivo and determine the impact of minor surgery on the microcirculation, we performed intravital microscopy over 25 days using a xenograft model of breast cancer tumor growth (MCF-7) in bone. After engraftment of tumors the mice were treated with a mastectomy versus no surgery. Tumor growth was accompanied by angiogenic sprouting and decreased vascular diameters while blood flow rate and tumor perfusion remained constant. Mastectomy initially led to a significant reduction of functional vascular density, increased vascular diameter, and decreased blood flow velocities. However, neither tumor growth nor tissue perfusion was different between the groups. The presented study corroborates the assumption that tumor microcirculation in bone exhibits similar time-dependent alterations compared to soft tissue tumors. A minor surgical intervention did not change tumor growth kinetics however microcirculatory properties were altered. Whether major surgery has an impact on tumor growth in bone should be clarified in further studies.

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“…Intravital observation has proven to be a successful approach to investigate microcirculatory properties [4,[33][34][35][36]. In our study, vascular analysis was longitudinally obtained on the same site, on the same animal.…”

Section: Discussionmentioning

confidence: 99%

Laser preconditioning of calvarial bone prior to an X‐ray radiation injury: A preliminary in vivo study of the vascular response

et al. 2008

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Background and Objectives: Thermal preconditioning prior to injury induces a cytoprotective effect on soft tissues and promotes their recovery. Lasers are an adequate tool to generate controlled and reproducible heat. X-ray irradiation induces a chronic antiangiogenic effect on bone, affecting its healing and remodeling processes. The aim of this study was to investigate the effect of laser preconditioning on the re-vascularization of X-ray irradiated bone. Materials and Methods: A bone chamber was implanted onto the calvaria of rabbits to study the vascularization process. Digital pictures were taken of the vascular plexus at the target bone site using a modified digital camera. Vascular density (VD) was determined using image processing. It was defined as the ratio of blood vessel pixels to the total number of pixels to the region of interest. Laser preconditioning was performed with a diode laser (810 nm, 2 W, 3 seconds, 48 J/cm 2 , 4 mm). A 12-week follow-up study was performed on 20 rabbits divided into four groups: #1: control group (n ¼ 5); #2: laser irradiation alone (n ¼ 5). #3: X-ray radiation (18.75 Gy) alone (n ¼ 5), #4: laser preconditioning 24 hours prior to X-ray radiation (n ¼ 5). Results: VD remained stable during the 12-week follow up for group #1. No significant difference was observed between laser irradiation group (#2) and control group (#1) (P > 0.5). The angiolytic action of X-ray radiation was confirmed in groups #3 and #4, which were statistically different from group #1 (P<0.001). However, the decrease of the vascularization was limited in group #4 highlighting a different evolution between group #3 and #4 (P<0.05). These results were confirmed by histological analysis. Discussion and Conclusion: The bone chamber is an effective reproducible method for the longitudinal analysis of the dynamics of vascularization. Our findings have shown that laser preconditioning is capable of preserving vascularization in an X-ray irradiated bone site, thus suggesting a novel approach for promoting the healing of bone tissue in which the vascular supply has been damaged.

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Femur window—a new approach to microcirculation of living bone in situ

Cited by 32 publications

References 50 publications

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Increased accumulation of magnetic nanoparticles by magnetizable implant materials for the treatment of implant-associated complications

Microcirculation of secondary bone tumors in vivo: The impact of minor surgery at a distal site

Laser preconditioning of calvarial bone prior to an X‐ray radiation injury: A preliminary in vivo study of the vascular response

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