An Animal Model of Human Peripheral Arterial Bending and Deformation.

BACKGROUND: Designing peripheral arterial stents has proved challenging, as implanted devices will repetitively and unpredictably deform and fatigue during movement. Preclinical testing is often inadequate, given the lack of relevant animal models. The purpose of this study was to test the hypothesis that deformation of the human peripheral vasculature could be qualitatively and quantitatively modeled using an experimental animal. METHODS: Anteroposterior contrast angiography was performed in domestic Landrace-Yorkshire farm pigs. Images were obtained with the hind limbs naturally extended then repeated, (1) flexed approximately 90° at the hip and knee, (2) overflexed in a nonphysiological fashion. Quantitative vascular angiographic analysis was utilized to measure arterial diameter, length, and deformation. Percent axial arterial compression and bending were assessed. RESULTS: Eight iliofemoral arteries in four animals were imaged. Mean luminal diameters of the iliac and femoral segments in the neutral position were 5.4 ± 0.5 mm and 4.6 ± 0.5 mm. Hind limb physiologic flexion induced profound arterial compression, 17 ± 8% and 29 ± 6% and bending, 36°±10° and 76° ± 13° within the iliac and femoral segments, respectively. With extreme flexion, the femoral artery could be reliably bent >90°. The observed findings exceeded the deformation observed historically within the human superficial femoral (∼5% compression and 10° bending) and popliteal artery (∼10% compression and 70° bending). CONCLUSIONS: Significant nonradial deformation of the porcine iliofemoral arteries was observed during manual hind limb flexion and exceeded that typically observed in humans. This model constitutes a "worst case" scenario for testing deformation and fatigue of intravascular devices indicated for the human peripheral vasculature.

Murine preosteoblast differentiation induced by a peptide derived from bone morphogenetic proteins-9.

Bone morphogenetic proteins (BMPs) increase the differentiation of osteoblasts implicated in bone formation and repair. In a previous study, we demonstrated that a peptide derived from BMP-9 (pBMP-9) at 400 ng/mL inhibited murine preosteoblasts MC3T3-E1 proliferation. Here, we compared the effects of equimolar concentrations of BMP-2 (50 ng/mL), BMP-9 (42.3 ng/mL), and pBMP-9 (4.52 ng/mL) on the differentiation of MC3T3-E1 in a serum-free medium. Like BMP-2, BMP-9 and pBMP-9 activated the Smad pathway. In contrary to BMP-2, the Smad phosphorylation induced by BMP-9 and pBMP-9 is not prevented by noggin, an extracellular antagonist of BMP-2. Further, BMP-9 and pBMP-9 increased, dose dependently, alkaline phosphatase activity, an early marker of osteoblast differentiation, after 1 day. Quantitative real-time polymerase chain reaction analysis demonstrated that BMP-2, BMP-9, and pBMP-9 (4.52 or 400 ng/mL) all activated the transcription of Runx2, Osterix, type I collagen alpha1 chain, and Osteocalcin genes within day 6. Alizarin red S quantification demonstrated that pBMP-9 (400 ng/mL) and pBMP-9 (4.52 ng/mL) allowed a slight deposition of Ca(2+) in the extracellular matrix of cells within 12 and 18 days, respectively. Therefore, pBMP-9 might be a promising replacement for costly BMP in tissue engineering applications that require a well-defined serum-free medium.