Effect of Inter-Fragmentary Gap Size on Neovascularization During Bone Healing: A Micro-CT Imaging Study.

Introduction: Neovascularization of the fracture site is of great importance for bone healing and could be influenced by local mechanical environment such as fixation stability and inter-fragmentary gap size. This study aims to reconstruct the neovascularization of the fracture site and explore the effect of inter-fragmentary gap size on the spatiotemporal structure of vascularity during bone healing. Methods: Osteotomy was performed on 36 Sprague-Dawley (SD) rats on the right tibial diaphysis, and the fracture was given stable fixation with two different inter-fragmentary gap sizes. SD rats received stable fixation with either a small-sized inter-fragmentary gap (FSF1, 1 mm, n = 18) or a large-sized one (FSF3, 3 mm, n = 18). The left hind limbs were treated as the control group (CON). The animals were killed at different time points (2, 4, and 6 weeks postoperatively, n = 6, respectively) for vascular perfusion and micro-CT imaging. Results: (a) At week 2 and 4, FSF1 group showed significantly higher vessel volume ratio (VV/TV) and vessel surface density (VS/TV) values than both CON and FSF3 group; there was no significant difference in either VV/TV or VS/TV values between CON and FSF3 groups. (b) At week 6, both FSF1 and FSF3 groups showed significantly higher VV/TV and VS/TV values than CON group; FSF3 group had a significantly higher VV/TV value than FSF1 group. Conclusion: Different inter-fragmentary gap sizes greatly affect the timing of angiogenesis at the fracture site. Stable fixation with a small inter-fragmentary gap (1 mm) benefits neovascularization at the early stages during bone healing and reconstruction, while stable fixation with a large inter-fragmentary gap (3 mm) delays the occurrence of angiogenesis to a later phase.

Mitigation of Articular Cartilage Degeneration and Subchondral Bone Sclerosis in Osteoarthritis Progression Using Low-Intensity Ultrasound Stimulation.

The purpose of this study was to evaluate the effect of low-intensity ultrasound on articular cartilage and subchondral bone alterations in joints under normal and functional disuse conditions during osteoarthritis (OA) progression. Total of thirty 5-mo-old female Sprague-Dawley rats were randomly assigned to six groups (n = 5/group): age-matched group, OA group, OA + ultrasound (US) group, hindlimb suspension (HLS) group, HLS + OA group and HLS + OA + US group. The surgical anterior cruciate ligament was used to induce OA in the right knee joints. After 2 wk of OA induction, low-intensity ultrasound generated with a 3-MHz transducer with 20% pulse duty cycle and 30 mW/cm2 acoustic intensity was delivered to the right knee joints for 20 min a day, 5 d a week for a total of 6 wk. Then, the right tibias were harvested for micro-computed tomography, histologic and mechanical analysis. Micro-computed tomography results indicated that the thickness and sulfated glycosaminoglycan content of cartilage decreased, but the thickness of the subchondral cortical bone plate and the formation of subchondral trabecular bone increased in the OA group under the normal joint use condition. Furthermore, histologic results revealed that chondrocyte density and arrangement in cartilage corrupted and the underlying subchondral bone increased during OA progression. These changes were accompanied by reductions in mechanical parameters in OA cartilage. However, fewer OA symptoms were observed in the HLS + OA group under the joint disuse condition. The cartilage degeneration and subchondral bone sclerosis were alleviated in the US treatment group, especially under normal joint use condition. In conclusion, low-intensity ultrasound could improve cartilage degeneration and subchondral sclerosis during OA progression. Also, it could provide a promising strategy for future clinical treatment for OA patients.

Pressure Drop in Tortuosity/Kinking of the Internal Carotid Artery: Simulation and Clinical Investigation.

Background. Whether carotid tortuosity/kinking of the internal carotid artery leads to cerebral ischemia remains unclear. There is very little research about the hemodynamic variation induced by carotid tortuosity/kinking in the literature. The objective of this study was to research the blood pressure changes induced by carotid tortuosity/kinking. Methods. We first created a geometric model of carotid tortuosity/kinking. Based on hemodynamic boundary conditions, the hemodynamics of carotid tortuosity and kinking were studied via a finite element simulation. Then, an in vitro system was built to validate the numerical simulation results. The mean arterial pressure changes before and after carotid kinking were measured using pressure sensors in 12 patients with carotid kinking. Results. Numerical simulation revealed that the pressure drops increased with increases in the kinking angles. Clinical tests and in vitro experiments confirmed the numerical simulation results. Conclusions. Carotid kinking leads to blood pressure reduction. In certain conditions, kinking may affect the cerebral blood supply and be associated with cerebral ischemia.

Effect of fixation on neovascularization during bone healing.

Fixation and vascularity after bone fracture are two critical factors for successful healing, and their influences on bone healing have been studied by many researchers. This research aims to obtain three-dimensional (3D) reconstruction images of neovascularization of the soft tissues surrounding the fracture with vascular perfusion and micro-computer tomography (micro-CT) imaging, and to investigate the effect of stable fixation on neovascularization and the pattern of vascularity during the process of bone healing. To accomplish this, 36 Sprague-Dawley (SD) rats underwent mid-shaft transverse osteotomy of the right tibia. Half of them received stable fixation with a newly custom-designed external fixator (FSF, the group of fracture with stable fixation), while the rest received no fixation (FNF, the group of fracture with no fixation). The results indicated that FNF samples had more transversal vascular distribution than FSF samples; FSF samples had more longitudinal vascular distribution than FNF samples; and the spatio-temporal pattern of vascularity in FSF samples was more similar to that in the control group (CON, the group without fracture) than that in FNF samples. At the time of 2 and 4 weeks postoperatively, FNF samples had significantly higher vessel volume ratio (VV/TV), larger vessel number (VN) and higher vessel surface density (VS/TV) than CON samples. At all sacrifice times, FSF samples contained significantly higher VV/TV, VN and VS/TV values compared with FNF samples. In summary, neovascularization and its pattern are obviously influenced by the mechanical fixation. Stable fixation can promote longitudinal vascularity pattern formation, which tends to be similar to the natural vascularity pattern, and this benefits the inter-fragmentary blood fluid connectivity during bone healing process.