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

Wound repair involves a series of overlapping phases that include inflammation, proliferation, and tissue remodeling, with the latter phase requiring months for proper healing. Delays in any of these processes can result in infection, chronic ulceration, and possible amputation. Diabetes is a major risk factor for improper wound repair, and impaired wound healing is a major complication for more than 26 million people in the US diagnosed with diabetes. Previous studies have demonstrated that the opioid antagonist naltrexone (NTX) dissolved in moisturizing cream reverses delays in wound closure in streptozotocin-induced type 1 diabetic (T1D) rats. NTX accelerated DNA synthesis and increased the number of epithelial and mast cells, as well as new blood vessel formation. In this study, remodeling was evaluated in T1D rats up to eight weeks after initial wounding. Twenty days following wounding, diabetic rats treated with vehicle had elevated numbers of MMP-2+ fibroblasts, suggesting delayed healing processes; birefringence of granulation tissue stained with Sirius red revealed diminished collagen formation and maturation. Wound tissue from NTX-treated T1D rats had comparable numbers of MMP-2+ fibroblasts to control specimens, as well as accelerated maturation of granulation tissue. The integrity of wounded skin was evaluated by tensile strength measurements. T1D resulted in delayed wound healing, and wounded skin that displayed reduced tensile strength relative to normal rats. Topical NTX applied to wounds in T1D rats resulted in enhanced collagen formation and maturation over a 60-day period of time. Moreover, the force required to tear skin of NTX-treated T1D rats was elevated relative to the force necessary to tear the skin of vehicle-treated T1D rats, and comparable to that for normal rats. These data reveal that complications in wound healing associated with T1D involve the novel OGF-OGFr pathway, and that topical NTX is an effective treatment to enhance wound healing.

Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats.

Successful tibiotalar joint fusion relies on adequate compression. Compression following joint preparation may be affected by the extent to which the fibula holds the joint out to anatomical length. The purpose of this study was to evaluate the effect of various distal fibula osteotomies on tibiotalar joint compression.

Distal fibula osteotomies improve tibiotalar joint compression: A biomechanical study in a cadaveric model.

The success of dental implant treatment is related to the complex 3-dimensional (3D) biomechanics of the implant-bone interaction. In this work, 3D numerical models are built based on micro X-ray computed tomography (micro-CT) images of a cadaveric mandible specimen with implants placed in it. The simulation results show that the computed strain values in bone are sensitive to the uncertainties in trabecular tissue modulus and fairly insensitive to the modulus of implants and teeth and the detailed geometry of the fixed boundary condition. A bone-volume-fraction (BV/TV) based method is proposed to assign the tissue moduli of bone elements based on their BV/TV to increase the connectivity of the mesh and to improve the accuracy of the models. These models are potentially powerful for calculating the 3D full-field bone strain under implant loading, enabling in silico testing of different implant designs, but demand validation of the models. The computed results reveal high strain concentration at bone-implant contact areas and, more importantly, in the buccal (lip-side) bone that is not making contact with the implant. The computed strain concentration patterns are found to be in good agreement with the observations from our prior experiments using 3D full-field mechanical testing coupled with micro-CT and digital volume correlation. The buccal bone is thinner and less stiff than other areas of bone and is also the commonly observed area of bone resorption after dental implant treatment.

Voxel-based micro-finite element analysis of dental implants in a human cadaveric mandible: Tissue modulus assignment and sensitivity analyses.

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.

Lisfranc ligamentous injuries are complex, and their treatment, along with the preferred method of fixation, is controversial. Implementing a flexible synthetic augmentation device (fibertape) has been described as an alternative to traditional screw fixation. This biomechanical study evaluated two fibertape devices with interference screw fixation: InternalBrace, and InternalBrace with supplementary intercuneiform stabilization.

Article	Year
Topical treatment with the opioid antagonist naltrexone accelerates the remodeling phase of full-thickness wound healing in type 1 diabetic rats. Experimental biology and medicine (Maywood, N.J.)\| PubMed ID: 23986225	2013
Distal fibula osteotomies improve tibiotalar joint compression: A biomechanical study in a cadaveric model. Clinical biomechanics (Bristol, Avon)\| PubMed ID: 30658156	2019
Voxel-based micro-finite element analysis of dental implants in a human cadaveric mandible: Tissue modulus assignment and sensitivity analyses. Journal of the mechanical behavior of biomedical materials\| PubMed ID: 30925312	2019
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
Biomechanical Comparison of Fibertape Device Repair Techniques of Ligamentous Lisfranc Injury in a Cadaveric Model. Injury\| PubMed ID: 33745699	2021

Gregory S. Lewis

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