Modulations of fluid flow inside the bone intramedullary cavity has been found to stimulate bone cellular activities and augment bone growth. However, study on the efficacy of the fluid modulation has been limited to external syringe pumps connected to the bone intramedullary cavity through the skin tubing. We report an implantable magnetic microfluidic pump which is suitable for in vivo studies in rodents. A compact microfluidic pump (22 mm diameter, 5 mm in thickness) with NdFeB magnets was fabricated in polydimethylsiloxane (PDMS) using a set of stainless-steel molds. An external actuator with a larger magnet was used to wirelessly actuate the magnetic microfluidic pump. The characterization of the static pressure of the microfluidic pump as a function of size of magnets was assessed. The dynamic pressure of the pump was also characterized to estimate the output of the pump. The magnetic microfluidic pump was implanted into the back of a Fischer-344 rat and connected to the intramedullary cavity of the femur using a tube. On-demand wireless magnetic operation using an actuator outside of the body was found to induce pressure modulation of up to 38 mmHg inside the femoral intramedullary cavity of the rat.

BACKGROUND Interleukin‐1 (IL‐1) is a pro‐inflammatory cytokine that plays a role in systemic and local inflammatory responses, inhibiting vascular contractility and inducing vascular dysfunction. Interleukin‐1 receptor antagonists (IL‐1RA) block IL‐1 signaling by binding to the IL‐1 receptor. Thus, IL‐1RA may have protective effects on vascular function during bone healing. We sought to determine the influence of IL‐1RA on vasodilator capacity of the femoral principal nutrient artery (i.e., PNA) following a bone defect. Additionally, we sought to determine the influence of IL‐1RA administration on macrovascular function (i.e., aortic stiffness). METHODS Young (6 months) and old (24 months) male Fischer‐344 rats were randomly assigned to 1) young control (YC, n=7–8), young interleukin‐1 receptor antagonism (Y_IL‐1RA, n=5–7), old control (OC, n=5–6), and old interleukin‐1 receptor antagonism (O_IL‐1RA, n=5–10). Under anesthesia (2.0% isoflurane to O2 balance), rats underwent surgery to create a small bone defect in the right femur. During recovery, the control and IL‐1RA groups received PBS (100 μl/day, i.p.) or IL‐1RA (3 μg/kg, i.p.), respectively, 3 days/week for 3 weeks. To assess arterial stiffness in the aorta, pulse wave velocity (PWV; cm/sec) was measured prior to the surgery and before sacrifice. At sacrifice, right femoral PNAs were isolated and cannulated to assess endothelium‐dependent (acetylcholine [ACh]: 10−9 – 10−4 M) and endothelium‐independent (DEA NONOate [DEA]: 10−10 – 10−4 M) vasodilation. A One‐Way ANOVA and Repeated Measures ANOVAs were performed. Alpha was set a priori at p<0.05 and tendencies (p<0.10) are reported. RESULTS Body mass was higher (p<0.05) in the old (OC, 401±15 g and O_IL‐1RA, 410±10 g) vs. young (YC, 351±6 g and Y_IL‐1RA, 354±9 g) rats, but did not differ between the age‐matched groups. The maximal diameters of the PNA did not differ among groups (YC, 209±17 μm; Y_IL‐1RA, 209±15 μm; OC, 212±8 μm; O_IL‐1RA, 238±11 μm). IL‐1RA administration had no effect on endothelium‐dependent vasodilation of the femoral PNA, however, there was a tendency (p=0.056) for reduction in O_IL‐1RA vs. YC. Endothelium‐independent vasodilation was augmented (p<0.05) in OC vs. all other groups and was impaired (p<0.05) in O_IL‐1RA vs. OC. PWV was higher (p<0.05) in the old (OC, 478±10 cm/sec and O_IL‐1RA, 452±8 cm/sec) vs. young (YC, 396±10 cm/sec and Y_IL‐1RA, 369±10 cm/sec) groups, indicating greater aortic stiffness. In addition, there were tendencies for reduced aortic stiffness by 6.8% and 5.5% in Y_IL‐1RA (p=0.061) and O_IL‐1RA (p=0.056), respectively, vs. their age‐matched controls. CONCLUSIONS 1) IL‐1RA treatment reduced endothelium‐independent vasodilation of the femoral PNA (i.e., the microvasculature) in old animals. 2) Aortic stiffness was augmented as a function of advanced age. 3) 3‐weeks of IL‐1RA treatment tended to reduce stiffness in the macrovasculature of both young and old rats. Support or Funding Information Grant Support: American Heart Association: 16IRG27550003

No abstract

BACKGROUNDPrevious studies demonstrated that chronic increases and decreases in bone intramedullary pressure (IMP) augments and reduces bone mass, respectively. Parathyroid hormone (PTH) plays a central role in the regulation of bone remodeling and augments bone mass. We previously reported augmented vasodilation of the femoral principal nutrient artery (PNA) to cumulative doses of PTH 1‐84, PTH 1‐34 and PTHrP 1‐34. In addition, bone perfusion is augmented following a bolus dose of PTH. Since PTH increases vasodilation and blood flow, we sought to assess its effects on bone IMP. The purpose of the study was to sequentially examine IMP in rat femora following PTH administration.METHODSMale Wistar rats (3–5 months) were randomly divided into the following groups: Control (CON, n = 7), PTH120 (n = 7), PTH150 (n = 7), and PTH330 (n = 7). Rats were anesthetized (2% isoflurane to O2 balance) and right femoral shafts were catheterized. At this time, the PTH groups received PTH 1‐84 (100 μg/kg, s.c.) and CON received PBS (100 μl, s.c.). The rats were sacrificed 120, 150 and 330 minutes following surgery. Just prior to sacrifice, the catheter was connected to a pressure transducer and in vivo IMP (mmHg) was recorded (PowerLab, AD Instruments) in the conscious rodents. The last 10 minutes of data were averaged and reported. Alpha level was set a priori at p<0.05 and One‐way ANOVA and Student Newman‐Keuls post hoc were performed to determine group differences.RESULTSBody mass did not differ among groups: CON, 478 ± 8 g; PTH120 474 ± 9 g; PTH150, 458 ± 6 g; PTH330, 488 ± 4 g. IMP was augmented (p<0.05) at PTH120 (33 ± 3 mmHg), PTH150 (35 ± 6 mmHg), PTH330 (41 ± 4 mmHg) vs. CON (20 ± 3 mmHg). IMP did not differ among the PTH groups.CONCLUSIONPTH increased bone IMP and sustained this response for up to 5 1/2 hours (i.e., 330 min) following administration. This increase in pressure corresponds with reports of enhanced vasodilation and bone perfusion following bolus administration of PTH. Given the bone altering effects of chronic IMP modulation, enhanced IMP with PTH administration may represent another mechanism by which it induces bone anabolism.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

BACKGROUND A pro‐inflammatory marrow microenvironment presumably augments ossification in bone marrow blood vessels. We speculate that ossifying blood vessels results in bone‐like particles (i.e., ossified particles, OSP) in the peripheral blood. By performing bone marrow ablation (BMA) and administering an interleukin‐1 receptor antagonist (IL‐1RA) during recovery, we sought to reduce the number of OSP in the circulation. METHODS Young (6‐mon) and old (24‐mon) male Fischer‐344 rats were assigned accordingly: Control (young CON, n=10; old CON, n=8), IL‐1RA (young, n=11; old, n=8), BMA (young, n=12; old, n=7) and combined treatment (young IL‐1RA+BMA, n=8; old IL‐1RA+BMA, n= 8). In the BMA and IL‐1RA+BMA rats, bone marrow in the right femoral shaft was ablated. During 3 weeks of recovery, CON and BMA rats received PBS (100 μL, 3 d/wk, i.p.), while IL‐1RA and IL‐1RA+BMA rats received the antagonist (3 μg/kg, 3 d/wk, i.p.). At sacrifice, left ventricular whole blood samples were collected. Plasma IL‐1α and IL‐1β were measured by ELISA. Five‐hundred microliters of blood were prepared for flow cytometry and OSP were sorted to obtain a count. The diameters of OSP were determined with a Cellometer. Some samples were pooled to meet the minimum detection threshold. These data are expressed as a percent of the total OSP count according to diameter, i.e., % OSP per 0‐14µm, 15‐30µm, 31‐45µm, and 46‐60µm. ELISA data were analyzed by two‐way ANOVA using SPSS (v. 25). The OSP count distributions were highly positively skewed with a mean and variance indicating overdispersed data. Therefore, negative binomial models were used to compare OSP count and % OSP using SAS GENMODE (v. 9.4). Data are presented as Means ± Standard Error. RESULTS Main effects for Age and Condition were detected in the ELISAs. Plasma IL‐1α did not differ; however, IL‐1β was higher (p<0.05) in Old (30.8±4.6 pg/mL) vs. Young (15.0±4.3 pg/mL). For Condition, IL‐1RA+BMA (49.6±14.1 pg/mL) had higher (p<0.05) plasma IL‐1α vs. CON (7.5E‐15±12.7 pg/mL) and IL‐1RA (9.4±13.2 pg/mL), and both CON (31.7±6.1 pg/mL) and IL‐1RA (41.2±6.3 pg/mL) had higher plasma IL‐1β vs. BMA (6.5±5.8 pg/mL) and IL‐1RA+BMA (12.3±6.8 pg/mL). For the OSP, Age x Condition interactions were detected. OSP count was higher (p<0.05) in Old IL‐1RA+BMA (3977±1631) vs. all other groups except Old IL‐1RA (1422±476). In addition, OSP count was higher (p<0.05) in Old IL‐1RA vs. Young IL‐1RA (212±67), Young BMA (276±80), and Young IL‐1RA+BMA (298±106). OSP count did not differ between Young CON (399±134) and Old CON (561±199). Analysis of % OSP revealed a main effect for diameter. Of the total in circulation, 38.4±7.8% were 15‐30µm, higher (p<0.05) than those 31‐45µm (5.7±1.2%) and 46‐60µm (2.2±0.5%). In addition, the % OSP 0‐14 µm (25.7±3.8%) were higher (p<0.05) vs. 31‐45µm and 45‐60µm. Further, the % OSP 31‐45µm was higher (p<0.05) vs. 46‐60µm. CONCLUSION Plasma concentrations of IL‐1α and IL‐1β varied with age and condition. Treatment with the IL‐1RA in old rats exacerbated the number of OSP in cir...