Quantifying Vascular Changes Surrounding Bone Regeneration in a Porcine Mandibular Defect Using Computed Tomography.

Angiogenesis is a critical process essential for optimal bone healing. Several in vitro and in vivo systems have been previously used to elucidate some of the mechanisms involved in the process of angiogenesis, and at the same time, to test potential therapeutic agents and bioactive factors that play important roles in neovascularization. Computed tomography (CT) is a noninvasive imaging technique that has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, such as bone formation within bony defects. Unfortunately, to date, angiogenesis evaluation relies primarily on histology, or ex vivo imaging and few studies have utilized CT to qualitatively and quantitatively study the vascular response during bone repair. In the current study a clinical CT-based technique was used to evaluate the effects of rhBMP-2 eluting graft treatment on soft tissue vascular architecture surrounding a large segmental bone defect model in the minipig mandible. The objective of this study was to demonstrate the efficacy of contrast-enhanced, clinical 64-slice CT technology in extracting quantitative metrics of vascular architecture over a 12-week period. The results of this study show that the presence of rhBMP-2 had a positive effect on vessel volume from 4 to 12 weeks, which was explained by a concurrent increase in vessel number, which was also significantly higher at 4 weeks for the rhBMP-2 treatment. More importantly, analysis of vessel architecture showed no changes throughout the duration of the study, indicating therapeutic safety. This study validates CT analysis as a relevant imaging method for quantitative and qualitative analysis of morphological characteristics of vascular tissue around a bone healing site. Also important, the study shows that CT technology can be used in large animal models and potentially be translated into clinical models for the development of improved methods to evaluate tissue healing and vascular adaptation processes over the course of therapy. This methodology has demonstrated sensitivity to tracking spatial and temporal changes in vascularization and has the potential to be applied to studying changes in other high-contrast tissues as well. Impact Statement Tissue engineering solutions depend on the surrounding tissue response to support regeneration. The inflammatory environment and surrounding vascular supply are critical to determining if therapies will survive, engraftment occurs, and native physiology is restored. This study for the first time evaluates the blood vessel network changes in surrounding soft tissue to a bone defect site in a large animal model, using clinically available computed tomography tools and model changes in vessel number, size, and architecture. While this study focuses on rhBMP2 delivery impacting surrounding vasculature, this validated method can be extended to studying the vascular network changes in other tissues as well.

Total knee arthroplasty for neuropathic (Charcot) joints.

The clinical and radiographic results of 40 modern design condylar total knee arthroplasties (TKAs) in 29 patients with a confirmed diagnosis of Charcot joint were reviewed. The followup averaged 7.9 years (range, 2-15 years) for clinical and 6.4 years (range, 2-15) for radiographic surveillance. There was a significant improvement in Knee Society pain and function scores and ROM after knee arthroplasty. Extensive bone fragmentation and bone defect was present in 38 knees (95%). Metal wedge augments (10 knees, eight patient), autologous bone grafting (17 knees, 13 patients), and bone allografts (two knees, two patients) were used to reinforce the bony defects. Ligamentous instability necessitated the use of long stem components in 27 knees and rotating hinge prostheses in five knees. There were six reoperations for periprosthetic fracture (two knees, two patients), aseptic loosening (two knees, two patients), instability (one knee, one patient), and deep infection (one knee, one patient). Total knee arthroplasty may be offered to a select group of patients with end-stage neuropathic arthropathy. The basic principles of knee arthroplasty in restoring limb alignment, reinforcing bony defects by bone grafting or augmented prostheses, careful ligamentous balancing, and appropriate selection of constrained prostheses particularly are important in these patients. The technical challenges encountered during TKA in patients with neuropathic arthropathy, particularly in those with significant deformities, can require skills, implant systems, and methods usually reserved for complex revision arthroplasty.