Tissue engineering offers an attractive alternative for treatment of chronic nonhealing diabetic ulcers, which account for more than 27% of the $10.9 billion total diabetic health care costs in the US annually [1]. The harsh environment of a diabetic ulcer is characterized by reduced expression of angiogenic factors, insufficient vascularization, excess protease activity, matrix degradation and hyperglycemia-induced cell apoptosis [2]. A major factor contributing to insufficient neovascularization in diabetic nonhealing wounds may be deficiency in the recruitment of endothelial cells (ECs) and endothelial precursor cells (EPCs) to the wound site [3]. Recent studies focusing on altering the wound’s cellular and molecular environment using bone-marrow-derived stem cells, growth factors (delivered either directly or using gene or cell therapy), bioengineered skin constructs, and biological matrices, such as collagen and hyaluronic acid gels had promising wound healing outcomes [4]. These studies suggest that strategies aimed at modifying the extracellular environment of the diabetic wound to enhance cell survival and angiogenesis are promising for development of new therapies for diabetic wound healing.

Endovascular repair of abdominal aortic aneurysm (AAA), where an endovascular graft (EVG) — a stented vascular graft — is implanted intraluminally into the AAA has shown excellent short term outcome. However, long term outcome of implanted EVGs is fraught with new complications, the most severe of which is endoleak from graft migration, which can lead to re-pressurization of the AAA and potentially rupture. Graft migration is defined as the distal drift of an implanted EVG of 5mm or more from its initial anchor site (Figure 1). There have been many design changes to help decrease the rate of EVG migration including the addition of proximal attachment barbs to grafts to help secure them to the aortic wall. However, studies show that freedom from migration rates have not significantly increased for those grafts containing barbs compared to grafts without barbs [1]. We believe that controlled studies of endovascular graft parameters can lead to improvements in its design that increase graft attachment strength and hence decrease the risk of migration. The aim of the current study was to assess a key design variable in barbed grafts namely, graft oversizing (GO), defined as the ratio of expanded graft dia to aorta dia. We sought to assess the relationship between GO and attachment strength in barbed EVGs. Specifically, we hypothesized that a high GO will impede the ability of the EVG barbs to effectively penetrate the aortic wall.

The glenohumeral joint is the most dislocated major joint in the body with most dislocations occurring anteriorly. [1] The anterior band of the inferior glenohumeral ligament (AB-IGHL) is the primary passive restraint to dislocation and experiences the highest strains during these events. [2,3] It has been found that injuries to the capsule following dislocation include permanent deformation, which increases joint mobility and contributes to recurrent instability. [4] Many current surgical repair techniques focus on plicating redundant tissue following injury. However, these techniques are inadequate as 12–25% of patients experience pain and instability afterwards and thus may not fully address all capsular tissue pathologies resulting from dislocation. [5] Therefore, the objective of this study was to determine the effect of permanent deformation on the mechanical properties of the AB-IGHL during a tensile elongation. Improved understanding of the capsular tissue pathologies resulting from dislocation may lead to new repair techniques that better restore joint stability and improve patient outcome by placating the capsule in specific locations.

The broad objective of our software, IA-FEMesh is to aid patient-specific finite element (FE) model development. Patient-specific models hold the potential to enable surgeons to plan care using objective analysis-based tools. Thus, they can better evaluate alternate surgical protocols and treatments, thereby contributing to improved surgical outcome. Our previous efforts were focused on projection techniques specific to the geometry under consideration [1]. The current meshing technique is the generalization of projection techniques that builds upon a multi-block approach, with considerable attention given to incorporating interactive tools to ease the model development process, thereby creating a user friendly approach to anatomic modeling.

Many researchers have studied the tibial passive motion, the boundaries of which are defined by various knee ligamentious and bony constraints [1, 2, 3]. The technique has been used in clinical practices and experimental research to assess injury and predict likely surgical outcomes [1, 2]. After total knee replacement surgery (TKR), the implants’ design features and altered ligamentious tension provide the joint constraint and stability. Therefore, the change in passive envelope of motion from the natural condition could be used to observe the altered constraints and stability achieved in TKR knees. The objective of this study was to assess the change in passive envelope of motion after TKR with two implant designs: cruciate retaining and posterior stabilized.

Massive rotator cuff tears are one of the most common shoulder problems among the elderly, leading to pain and disability of the upper extremity. Muscle transfer, which can compensate for some of the deficits, has been advocated as the primary treatment of irreparable massive rotator cuff tears or as a salvage procedure after failed repairs. Latissimus dorsi transfers offer a promising solution in the treatment of irreparable posterosuperior rotator cuff tears, resulting in pain relief and function improvement of patients with the tears. However, the clinical results are variable and the factors which determine outcome are poorly understood. Prior studies have revealed that the functional outcomes of latissimus dorsi transfers were adversely affected if there was a deficit in deltoid and teres minor muscles [1, 2]. For the patient with a deltoid injury, the transfer that follows a failed rotator cuff repair produces less functional improvement than if the transfer is performed as the primary treatment to repair the rotator cuff. It was revealed that the presence of a tear of the teres minor muscle might have some predictive value prior to surgery with regard to motion and function [1], whereas the degree of fatty infiltration also played a critical role after the transfer [2]. Outcomes of muscle transfers have been reported in the literature, but the effects of extrinsic muscle integrity on the functional outcomes in the latissumus dorsi transfer have not been addressed quantitatively. The purpose of this work was to study the effects of the extrinsic muscle integrity on the functional outcomes in the latissumus dorsi transfer using a three-dimensional integrated model of the upper extremity [3]. First, the effects of extrinsic muscle integrity on the preoperative functions of shoulders with massive rotator cuff tears were investigated. Second, these effects on the functional outcomes of muscle transfers were evaluated quantitatively.

Freezing of biological tissues occurs in cryomedicine applications such as cryosurgery and cryopreservation. Although cellular level biophysics during freezing and thawing (F/T) has been extensively studied, tissue level biophysics is not fully understood yet. Especially, the effects of F/T on the functionalities of tissue are not well understood so that the outcomes of cryomedicine applications are highly tissue-type dependent [1]. Although many of the functionalities are associated with the extracellular matrix (ECM), the effect of F/T on ECM microstructure has been overlooked. Quantitative understanding on the post-thaw ECM structure is rarely available, but it is essential to design and improve cryopresevation and cryotherapy protocols for a wide variety of native and engineered tissues.

Experimental testing with cadaveric tissue allows the application of controlled loads and/or motions while still maintaining the inherent variability in the anatomy and soft tissue of the specimens. Multi-axial dynamic loading of tissue allows for experiments to be conducted that simulate conditions approaching physiological. Knee simulators have been used to generate physiological loading on the human knee to study kinematics, soft tissue loading, and joint contact pressure. These machines have been used to investigate injury, surgical outcomes, and prosthetic design. While there are a number of different geometries for knee loading devices, most are based on the Oxford rig design [1] with a vertical orientation of the leg where the hip is able to translate up and down while allowing flexion at the hip, knee, and ankle. The foot or ankle can have a variety of constraints and degrees of freedom. One of the recent areas of interest in knee biomechanics is the role different structures of the knee play during deep knee flexion activities. This is of particular interest to the orthopedic industry because of the common complaint regarding a feeling of a loss of stability during high flexion activities for post-TKR patients and the prevalence of high-flexion activities in emerging worldwide markets. The objective of this abstract is to describe two knee loading devices that have been used to study knee biomechanics, and most recently high flexion motion, and present some representative data from these tools.

In orthodontics, patients are treated by moving teeth to improve esthetics and occlusion. Tooth displacement is one of the most important outcomes, and can be used to evaluate treatment strategies and orthodontic appliances. Thus, an accurate and reliable method for quantification of the three dimensional (3D) tooth displacements is of high interest [1].

Tissue engineering provides a means to create fully functional tissue-equivalents that can grow, repair and remodel in vivo . Our laboratory’s approach to fabricating artery- and heart valve-equivalents utilizes cell-seeded fibrin gels. However, even after 4–5 weeks of static incubation, the mechanical properties of these constructs are below those of native tissue. Previous studies in our laboratory have shown a significant role of mechanical stretching in improving properties of collagen-based tissue constructs (Isenberg and Tranquillo, 2003). We examined the effects of cyclic distention (CD) of cell-seeded fibrin-based tubular constructs (TC) and valve-equivalents (VE) after five weeks of culture. We used human dermal fibroblasts and porcine valve interstitial cells as the cell sources. Circumferential strain amplitudes from 2.5% to 15% were applied to evaluate the effects of CD on remodeling of the TC. We further hypothesized that during long-term conditioning, cells adapt to CD of constant strain amplitude, diminishing the remodeling into tissue. We tested this hypothesis by applying step-wise incremental CD (ICD) from 5%–15% strain amplitude and compared this group to a set of samples subject to CD of constant strain amplitude in this range. Based on the outcome of the cyclic distension study with tubular constructs, we applied CD to VE in a novel bioreactor.

Abdominal aortic aneurysm (AAA) is a complex disease defined as a pathological dilation of the vessel wall to larger than 150% of normal. Although the poor clinical outcomes associated with this disease are well known, a detailed understanding of the underlying mechanisms that lead to AAA development and expansion remains elusive. The purpose of this study was to determine if areas of increased protease expression correspond to locations of aortic stiffening and enlargement in a commonly used mouse model [1].

Cardiovascular disease has historically been the leading cause of death in the US [1], and coronary artery disease in particular accounts for over fifty percent of these deaths [1]. Since their approval in 1994, coronary stents have become one of the leading treatments for this disease. However, problems persist in both bare metal and drug-eluting stents (DESs) with long-term restenosis and thrombosis. It is well accepted that disruptions in arterial wall shear stress (WSS), especially low WSS, are linked to alterations in the endothelial cell layer, atherosclerosis, and thrombogenesis [2], although the exact mechanisms are still uncertain, and studies have shown that stent design is closely linked to clinical outcomes [3].

Analyses of orthopaedic devices and prostheses from surgical revisions (failures) have provided considerable and valuable information related to the causes of some unintended clinical outcomes. Thousands of explanted samples have been categorized and hundreds studied over past decades. Forensic approaches for determining cause-effect relationships specific to the prosthesis aspects of clinical performance could lead to recommendations of improvements of existing or design of new systems to further enhance clinical longevities. In the following we provide a summary of methodologies and example results from a series of recent retrieval studies aimed at the analysis of alternative bearing surfaces in orthopaedic implants.

Cardiovascular disease has historically been the leading cause of death in the US [1], and accounts for approximately one third of all deaths worldwide [2]. Coronary artery disease in particular accounts for over fifty percent of these deaths and in 2004 was the single largest killer, affecting approximately 15 million people every year [1]. Coronary stenting was approved in 1994 by the FDA, and has become one of the leading treatments for the disease. However, problems persist in both bare metal and drug-eluting stents (DESs) with restenosis and thrombosis. It is well accepted that disruptions in arterial wall shear stress (WSS), especially low WSS, are linked to alterations in the endothelial cell layer and ultimately disease [3], although the exact mechanisms are still uncertain. Additionally, studies have shown that stent design is closely linked to clinical outcomes [4].

Right ventricular (RV) dysfunction is a common cause of heart failure in patients with congenital heart defects and often leads to impaired functional capacity and premature death. Computational heart models have been developed to understand the complex blood flow and cardiac mechanical behaviors [2,4]. However, clinic-oriented patient-specific models with fluid-structure interactions which can be used to make accurate predictions for potential surgical outcome are still lacking in the literature and clinical practices. A novel modeling procedure is proposed to test the hypotheses that a) patient-specific computational RV/LV combination model based on pre-operation MRI data can provide accurate assessment of RV cardiac functions (measured by RV ejection fraction and stroke volume) and that b) the RV/LV model validated by pre-operation data can be used as the base model to perform virtual pulmonary valve insertion (PVI) and RV volume reduction surgery to optimize post-operative RV morphology and patch design prior to the actual operation and that this procedure will lead to improved recovery of RV functions. With validation, this modeling process could replace empirical and often risky clinical experimentation to examine the efficiency and suitability of various reconstructive procedures in diseased hearts.

Patellofemoral (PF) disorders remain complex and multifactorial. PF pathology, such as PF knee pain, excessive lateral pressure, and PF arthritis have been linked to excessive contact forces and pressure between the patella and femur [1]. Antero-medial transfer of the tibial tuberosity and tibial attachment of the patellar tendon is a procedure that was designed to reduce the PF contact pressure, thereby decreasing pain symptoms of early PF arthritis. The transfer procedure alters the angle between the patellar tendon and the quadriceps muscle force, and increases the patellar moment arm. These changes result in a reduction in the quadriceps force required for a given knee flexion strength, and in reduced contact pressure between the patella and femur. However, the tubercle movement also changes the flexion of the patella in the sagital plane, which alters not only regions of contact at various degrees of motion, but may also alter the contact area at these flexion ranges. PF forces, contact pressures and kinematics have been evaluated both prior to, and following, anteromedialization procedures in several cadaveric studies, e.g. [2]. Computational studies have evaluated the potential of anterior and medial tuberosity transfer to reduce PF contact pressure, including a study utilizing patient-specific models to analyze isolated anterior transfer at 15 and 20 mm, and combined antero-medial transfer at two different treatment levels for single, static flexion positions [3]. However, this study suggested that optimal tuberosity transfer required to decrease contact pressure was widely variable between patients and had less absolute decreases than earlier studies. This variability of contact pressure may translate clinically to patient comfort and thus, to maximize surgical outcome, it is likely necessary to identify a patient-specific parameter. Therefore, the purpose of the present study was to evaluate the feasibility of optimization, specifically simulated annealing, to determine the optimal amounts of anterior and medial transfer of the tibial tuberosity required to minimize peak patellofemoral contact pressure during a deep flexion cycle.

Recent surgical management of cancer tends toward minimally invasive surgical techniques since tumors can be detected smaller than ever due to the advance of cancer diagnostic technologies. Many of these surgical procedures are thermal therapies where a localized freezing or heating zone (i.e. thermal lesion) is created to destroy tumors without damaging adjacent normal tissues. The outcomes of these innovative and less invasive surgeries, however, are significantly impaired by the limited image-guidance of the thermal lesion during the procedures. Since the primary clinical objective of these surgeries is to eradicate diseased tissues while sparing the adjacent normal tissue, accurate intra-operative monitoring of the thermal lesion is critical. Moreover, in many surgical situations, sparing adjacent tissue is not only desired, but imperative since major blood vessels, nerve bundles and surrounding organs are susceptible to thermal injury. However, currently available monitoring techniques have limited accuracy or accessibility, and/or are not capable of monitoring the lesion in real-time during the procedure. In our recent study [1], we demonstrated the feasibility of non-invasive thermometry using quantum dot (QD) as temperature probe. Although its feasibility was demonstrated, several limitations should be addressed before more rigorous clinical applications. Especially the lower quantum yield of core/shell QDs should be significantly improved for deeper tissue imaging. In the present study, QD-embedded nano-composite particles were developed for deeper tissue imaging and its temperature dependent fluorescence was characterized.

Improvements in the prediction of thermal behavior during cryosurgery and cryopreservation can help improve the outcome of these cryobiological applications. The accuracy of the models depends on numerous factors including the kinetics and energy release during phase change phenomena and knowledge of thermal properties. Furthermore, connecting the thermal properties to crystalline, amorphous, and other phases adds an important mechanistic dimension that can also improve and direct an outcome. However, insufficient data for thermal properties in the subzero domain result in reliance on property estimations based usually upon tabulated water-ice data or weight averaged values from known materials primarily in temperature ranges above −40 °C [1]. This study focused on expanding the thermal properties database for both solutions and tissues. Results for Phosphate Buffered Saline (PBS) and porcine liver with glycerol at subzero temperatures (−150 ∼ 0 °C) are reported. The shifting of thermal property values due to sample crystallization, amorphous phase transition, and melting is discussed.

Ruptured intracranial aneurysms often have poor clinical outcome. International Study on Unruptured Intracranial Aneurysms has demonstrated the value of treatment for unruptured intracranial aneurysms and that aneurysms larger than 7mm may benefit from treatment. Although aneurysm size appears to be the major indication for rupture, other risk factors, including anatomical location and patient history, are also important in clinical evaluation and cannot be overlooked. Aneurysms at the anterior communicating artery (ACoA) especially have higher rupture risk and rupture at smaller sizes than other aneurysms.

Degenerative changes in the cervical spine due to aging are very common causes of neck pain in general population. Although many investigators have quantified the gross morphological changes in the disc with progressive degeneration, the biomechanical changes due to degenerative pathologies of the disc and its effect on the adjacent levels are not well understood. Despite many in vivo and in vitro techniques used to study such complex phenomena, the finite element (FE) method is still a powerful tool to investigate the internal mechanics and complex clinical situations under various physiological loadings particularly when large numbers of parameters are involved. The objective of the present study was to develop and validate a poroelastic FE model of a healthy C3-T1 segment of the cervical spine under physiologic moment loads. The model included the regional effect of change in the fixed charged density of proteoglycan concentration and change in the permeability and porosity due to change in the axial strain of disc tissues. The model was further modified to include various degrees of disc degeneration at the C5-C6 level. Outcomes of this study provided a better understanding on the progression of degeneration along the cervical spine by investigating the biomechanical response of the adjacent segments with an intermediate degenerated C5-C6 level.