Bryn Brazile

Investigating the Potential of Amnion-Based Scaffolds as a Barrier Membrane for Guided Bone Regeneration

Guided bone regeneration is a new concept of large bone defect therapy, which employs a barrier membrane to afford a protected room for osteogenesis and prevent the invasion of fibroblasts. In this study, we developed a novel barrier membrane made from lyophilized multilayered acellular human amnion membranes (AHAM). After decellularization, the AHAM preserved the structural and biomechanical integrity of the amnion extracellular matrix (ECM). The AHAM also showed minimal toxic effects when cocultured with mesenchymal stem cells (MSCs), as evidenced by high cell density, good cell viability, and efficient osteogenic differentiation after 21-day culturing. The effectiveness of the multilayered AHAM in guiding bone regeneration was evaluated using an in vivo rat tibia defect model. After 6 weeks of surgery, the multilayered AHAM showed great efficiency in acting as a shield to avoid the invasion of the fibrous tissues, stabilizing the bone grafts and inducing the massive bone growth. We hence concluded that the advantages of the lyophilized multilayered AHAM barrier membrane are as follows: preservation of the structural and mechanical properties of the amnion ECM, easiness for preparation and handling, flexibility in adjusting the thickness and mechanical properties to suit the application, and efficiency in inducing bone growth and avoiding fibrous tissues invasion.

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome: A historical perspective

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital defect of the Müllerian ducts characterized by uterovaginal agenesis and underdeveloped female genital organs. This paper is a tribute to the contributors of this condition - August Franz Joseph Karl Mayer, Karl Freiherr von Rokitansky, Hermann Küster and Georges André Hauser. In addition to their contributions, we have discussed findings and reports of similar defects from other important scientists (Hippocrates, Albucasis, etc.) dating as far back as 460B.C. We have also discussed the disease types and different classification systems including VCUAM and AFS/ASRM among others. Even with several surgical and non-surgical treatment options, there are still many questions that remain unanswered and very little is known about the etiology or genetic predisposition of this condition.

Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression

Understanding the passive mechanical properties of infarcted tissue at different healing stages is essential to explore the emerging biomaterial injection-based therapy for myocardial infarction (MI). Although rats have been widely used as animal models in such investigations, the data in literature that quantify the passive mechanical properties of rat heart infarcts is very limited. MI was induced in rats and hearts were harvested immediately (0 day), 7, 14 and 28 days after infarction onset. Left ventricle anterioapical samples were cut and underwent equibiaxial and non equibiaxial tension followed by uniaxial compression mechanical tests. Histological analysis was conducted to confirm MI and to quantify the size of the induced infarcts. Infarcts maintained anisotropy and the nonlinear biaxial and compressive mechanical behaviour throughout the healing phases with the circumferential direction being stiffer than the longitudinal direction. Mechanical coupling was observed between the two axes in all infarct groups. The 0, 7, 14 and 28 days infarcts showed 438, 693, 1048 and 1218kPa circumferential tensile moduli. The 28 day infarct group showed a significantly higher compressive modulus compared to the other infarct groups (p=0.0060, 0.0293, and 0.0268 for 0, 7 and 14 days groups). Collagen fibres were found to align in a preferred direction for all infarct groups supporting the observed mechanical anisotropy. The presented data are useful for developing material models for healing infarcts and for setting a baseline for future assessment of emerging mechanical-based MI therapies.

Experimental Evidence of Mechanical Isotropy in Porcine Lung Parenchyma

Pulmonary injuries are a major source of morbidity and mortality associated with trauma. Trauma includes injuries associated with accidents and falls as well as blast injuries caused by explosives. The prevalence and mortality of these injuries has made research of pulmonary injury a major priority. Lungs have a complex structure, with multiple types of tissues necessary to allow successful respiration. The soft, porous parenchyma is the component of the lung which contains the alveoli responsible for gas exchange. Parenchyma is also the portion which is most susceptible to traumatic injury. Finite element simulations are an important tool for studying traumatic injury to the human body. These simulations rely on material properties to accurately recreate real world mechanical behaviors. Previous studies have explored the mechanical properties of lung tissues, specifically parenchyma. These studies have assumed material isotropy but, to our knowledge, no study has thoroughly tested and quantified this assumption. This study presents a novel methodology for assessing isotropy in a tissue, and applies these methods to porcine lung parenchyma. Briefly, lung parenchyma samples were dissected so as to be aligned with one of the three anatomical planes, sagittal, frontal, and transverse, and then subjected to compressive mechanical testing. Stress-strain curves from these tests were statistically compared by a novel method for differences in stresses and strains at percentages of the curve. Histological samples aligned with the anatomical planes were also examined by qualitative and quantitative methods to determine any differences in the microstructural morphology. Our study showed significant evidence to support the hypothesis that lung parenchyma behaves isotropically.

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

Quantitative Analysis of Tissue Damage Evolution in Porcine Liver With Interrupted Mechanical Testing Under Tension, Compression, and Shear

In this study, the damage evolution of liver tissue was quantified at the microstructural level under tensile, compression, and shear loading conditions using an interrupted mechanical testing method. To capture the internal microstructural changes in response to global deformation, the tissue samples were loaded to different strain levels and chemically fixed to permanently preserve the deformed tissue geometry. Tissue microstructural alterations were analyzed to quantify the accumulated damages, with damage-related parameters such as number density, area fraction, mean area, and mean nearest neighbor distance (NND). All three loading states showed a unique pattern of damage evolution, in which the damages were found to increase in number and size, but decrease in NND as strain level increased. To validate the observed damage features as true tissue microstructural damages, more samples were loaded to the above-mentioned strain levels and then unloaded back to their reference state, followed by fixation. The most major damage-relevant features at higher strain levels remained after the release of the external loading, indicating the occurrence of permanent inelastic deformation. This study provides a foundation for future structure-based constitutive material modeling that can capture and predict the stress-state dependent damage evolution in liver tissue.

Infarcted rat myocardium: Data from biaxial tensile and uniaxial compressive testing and analysis of collagen fibre orientation.

Myocardial infarction was experimentally induced in rat hearts and harvested immediately, 7, 14 and 28 days after the infarction induction. Anterior wall infarct samples underwent biaxial tensile and uniaxial compressive testing. Orientation of collagen fibres was analysed following mechanical testing. In this paper, we present the tensile and compressive stress–strain raw data, the calculated tensile and compressive moduli and the measured angles of collagen orientation. The presented data is associated with the research article titled “Characterisation of the mechanical properties of infarcted myocardium in the rat under biaxial tension and uniaxial compression” (Sirry et al., 2016) [1].

Pelvic Floor Biomechanics from Animal Models

Pelvic organ prolapse (POP) is characterized by the failure of vaginal wall support and protrusion of the pelvic organs through the vaginal orifice. The exact etiology of POP remains elusive to date, and one of the primary hurdles is the limited availability of animal models, which provide a means to better understand the weakening of supportive tissues in POP and the mechanisms of treatment failures. Each animal model has its own set of advantages and disadvantages. In this chapter, we review the various animal models of POP and provide an indepth analysis of sheep as a robust large animal model for urogynecological research. The ease of handling, short lifespan, and relatively low costs are major advantages of rodent models, which have been used extensively to investigate connective tissue physiology and pathophysiology as it relates to POP. However, sheep have supporting structures for pelvic organs, as well as structural and mechanical properties more similar to humans. Many of the risk factors for sheep prolapse have close analogues in humans, including high fetal weight, obesity, dystocia, parity, and family history of prolapse. In addition, large animal models, such as sheep, are likely more appropriate for evaluation of novel therapeutic strategies for treatment. Future research using sheep and other animal models will illuminate the pathophysiology of POP as well as provide essential information on pelvic floor biomechanics and treatment efficacy.