assessment-of-bone-fracture-healing-using-micro-computed-tomography

Assessment of Bone Fracture Healing Using Micro-Computed Tomography

Micro-computed tomography (&#181;CT) is the most common imaging modality to characterize the three-dimensional (3D) morphology of bone and newly formed ...

The Pennsylvania State University College of Medicine

This paper reports the core-shell structure effects in calcium alginate (CaALG) microbeads due to the threshold water level for phase transition and correlates these properties with respect to pH and electrical conductivity. Further, in this study, we used a novel microfluidic device for drug release testing to study the programmed release of risedronate (RIS-anti-osteoporotic drug) encapsulated in pH-responsive CaALG-chitosan (CHT) microbeads. Our microfluidic device contains a single straight microchannel containing a steplike barrier design used to restrict the mobility of the microbeads at the sample detection zone. For optical and fluorescence microscopy, single fluorescently labeled CaALG-CHT microbead containing RIS was placed in the sample detection zone by flowing through the inlet port with ultrapure water. The RIS release behavior from the microbeads at different pH (2.1, 4, 6.8, and 7.4) conditions was determined by using a spectrophotometer connected to the outlet port of the device. Results of our first study showed that the decrease in the concentration of CaCl increases the swelling rate in CaALG microbeads. Maximum swelling was achieved with the lowest molar concentration of CaCl used for fabrication of CaALG microbeads. Further, electrical current-voltage characteristic shows the nature of ionic mobility with respect to varying levels of pH indicating electrokinetic forces developed in the CaALG microbeads. By using a microfluidic device for drug release testing, we demonstrated that a sustained release delivery system for RIS can be prepared by coating with pH-sensitive and biodegradable CaALG-CHT. The CaALG-CHT microbeads used for encapsulating RIS are resistant to the acidic environment of the stomach. This may improve the therapeutic effectiveness and reduce the gastric adverse effects associated with RIS by preventing its decomposition in the acidic condition of stomach. The newly developed microfluidic device for drug release testing may find applications in screening novel drugs and delivery systems.

Ionic Diffusion and Drug Release Behavior of Core-Shell-Functionalized Alginate-Chitosan-Based Hydrogel.

Impaired fracture healing in patients with obesity-associated type 2 diabetes (T2D) is a significant unmet clinical problem that affects millions of people worldwide. However, the underlying causes are poorly understood. Additionally, limited clinical information is available on how pre-diabetic hyperglycemia in obese individuals impacts bone healing. Here, we use the diet-induced obesity (DIO) mouse (C57BL/6J) model to study the impact of obesity-associated pre-diabetic hyperglycemia on bone healing and fibrillar collagen organization as healing proceeds from one phase to another. We show that DIO mice exhibit defective healing characterized by reduced bone mineral density, bone volume, and bone volume density. Differences in the healing pattern between lean and DIO mice occur early in the healing process as evidenced by faster resorption of the fibrocartilaginous callus in DIO mice. However, the major differences between lean and DIO mice occur during the later phases of endochondral ossification and bone remodeling. Comprehensive analyses of fibrillar collagen microstructure and expression pattern during these phases, using a set of complementary techniques that include histomorphometry, immunofluorescence staining, and second harmonic generation microscopy, demonstrate significant defects in DIO mice. Defects include strikingly sparse and disorganized collagen fibers, as well as pathological accumulation of unfolded collagen triple helices. We also demonstrate that DIO-associated changes in fibrillar collagen structure are attributable, at least in part, to the accumulation of advanced glycation end products, which increase the collagen-fiber crosslink density. These major changes impair fibrillar collagens functions, culminating in defective callus mineralization, remodeling, and strength. Our data extend the understanding of mechanisms by which obesity and its associated hyperglycemia impair fracture healing and underline defective fibrillar collagen microstructure as a novel and important contributor.

Aberrant structure of fibrillar collagen and elevated levels of advanced glycation end products typify delayed fracture healing in the diet-induced obesity mouse model.

Article	Year
Ionic Diffusion and Drug Release Behavior of Core-Shell-Functionalized Alginate-Chitosan-Based Hydrogel. ACS omega\| PubMed ID: 31956826	2020
Aberrant structure of fibrillar collagen and elevated levels of advanced glycation end products typify delayed fracture healing in the diet-induced obesity mouse model. Bone\| PubMed ID: 32439570	2020

Deepak Kumar Khajuria

Biography

JoVE Journal Publications

Other Publications