Loraine LY Chiu

• B.A.Sc., M.A.Sc., Ph.D.
• Research Associate at St. Michael's Hospital

Cell cycle synchronization allows cells in a culture, originally at different stages of the cell cycle, to be brought to the same phase. It is normally performed by applying cell cycle arresting chemical agents to cells cultured in monolayer. While effective, isolated chondrocytes tend to dedifferentiate when cultured in monolayer and typically req...

Mechanical stimulation is commonly used in cartilage tissue engineering for enhancing tissue formation and improving the mechanical properties of resulting engineered tissues. However, expanded chondrocytes tend to dedifferentiate and lose expression of their primary cilia, which is necessary for chondrocyte mechanotransduction. As treatment with l...

Objective To evaluate the effect of Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel modulation on mesenchymal stromal cell (MSC)-derived neocartilage. Methods RT-PCR was performed to evaluate mRNA levels of chondrogenic, hypertrophic and candidate mechanoresponsive genes in equine neocartilage sheets exposed to pulses of the TRPV4...

Introduction : In vitro tissue engineering of osteochondral implants is an attractive solution to circumvent the limitations of these therapies by providing readily available grafts for patients. Objective : Generate and evaluate the mechanical properties of osteochondral constructs through double indentation and stress-relaxation tests. Methods...

Objective: Although tissue engineering is a promising option for articular cartilage repair, it has been challenging to generate functional cartilaginous tissue. While the synthetic response of chondrocytes can be influenced by various means, most approaches treat chondrocytes as a homogeneous population that would respond similarly. However, isol...

A major shortcoming in cartilage tissue engineering is the low biosynthetic response of chondrocytes. While different strategies have been investigated, a novel approach may be to control nutrient metabolism. Although known for their anaerobic metabolism, chondrocytes are more synthetically active under conditions that elicit mixed aerobic–anaerobi...

Silicone rubber’s silicone-oxygen backbones give unique material properties which are applicable in various biomedical devices. Due to the diversity of potential silicone rubber compositions, the material properties can vary widely. This paper characterizes the dielectric and mechanical properties of two different silicone rubbers, each with a diff...

Despite the potential of tissue engineering approaches for cartilage repair, a major shortcoming is the low biosynthetic response of chondrocytes. While different strategies have been investigated to upregulate tissue formation, a novel approach may be to control nutrient metabolism. Although known for their anaerobic metabolism of glucose, chondro...

This study evaluates the hemostatic properties of tantalum-containing mesoporous bioactive glasses (Ta-MBGs) through a suite of in-vitro methods: hemolysis percentage, zeta potential, blood coagulation assays (Activated Partial Thromboplastin Time – APTT and Prothrombin Time - PT) and cytotoxicity tests. Five compositions of Ta-MBG, with x mol% Ta...

Tissue engineering is a promising option for cartilage repair. However, several hurdles still need to be overcome to develop functional tissue constructs suitable for implantation. One of the most common challenges is the general low capacity of chondrocytes to synthesize cartilage‐specific extracellular matrix (ECM). While different approaches hav...

Titanium‐containing borate bioactive glass scaffolds (0, 5, 15, and 20 mol %, identified as BRT0, BRT1, BRT3, and BRT4) with a microstructure similar to that of human trabecular bone were prepared and evaluated in vitro for potential bone loss applications in revision total knee arthroplasty (rTKA). Methyl thiazolyl tetrazolium (MTT) cell viability...

Objectives Current strategies for external ear reconstruction can lead to donor site morbidity and/or surgical complications. Tissue‐engineered auricular tissues may provide readily available reconstructive materials that resemble native auricular tissue, which is composed of a cartilaginous region sandwiched between two perichondrial layers. We pr...

Dynamic mechanical stimulation has been an effective method to improve the growth of tissue engineering cartilage constructs derived from immature cells. However, when more mature cell populations are used, results are often variable due to the differing responses of these cells to external stimuli. This can be especially detrimental in the case of...

Objectives Tissue engineering of auricular cartilage has great potential in providing readily available materials for reconstructive surgeries. As the field of tissue engineering moves forward to developing human tissues, there needs to be an interspecies comparison of the native auricular cartilage in order to determine a suitable animal model to...

Objective: Cartilage tissue engineering is a promising approach to provide suitable materials for nasal reconstruction; however, it typically requires large numbers of cells. We have previously shown that a small number of chondrocytes cultivated within a continuous flow bioreactor can elicit substantial tissue growth, but translation to human cho...

Background: The use of chondrocytes for cartilage tissue engineering is hampered by the limited number of chondrocytes that can be harvested and potential dedifferentiation during cell expansion. While stem

-Hydrogels are being actively investigated for direct delivery of cells or bioactive molecules to the heart post-myocardial infarction (MI) to prevent cardiac functional loss. We postulate that immobilization of the pro-survival angiopoietin-1-derived peptide, QHREDGS, to a chitosan-collagen hydrogel could produce a clinically translatable thermo-r...

Motivation for cardiac tissue regeneration in vitro Myocardial infarction (MI) leads to the death of cardiomyocytes, and the infarct area becomes replaced by a fibroblastic scar tissue that has no contractile function. This reduces the pumping ability of the heart and the cardiac output. In addition, the scar tissue thins due to the lack of vascula...

Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for novel treatment options. Since the only viable treatment option for end-stage heart failure is a heart transplant, cardiac tissue engineering emerged from the need to develop alternative sources and methods of replacing tissue damag...

In surgical repair for heart disease, it is often necessary to implant conduits or correct tissue defects. Commonly used graft materials include artifi cial grafts, autologous tissues, allografts and xenografts. However, none of these offer growth potential, and all are associated with varying levels of thrombogenicity and susceptibility to infecti...

Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternative sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-sta...

In this review, we will discuss the current developments in the field of cardiac tissue engineering, with a focus on the studies over the past 5 years. The key advances in cardiac tissue engineering include the generation of human cardiomyocytes from embryonic stem cells and induced pluripotent stem cells, the development of biomaterials that have...

Vascularization is critical for the survival of engineered tissues in vitro and in vivo. In vivo, angiogenesis involves endothelial cell proliferation and sprouting followed by connection of extended cellular processes and subsequent lumen propagation through vacuole fusion. We mimicked this process in engineering an organized capillary network anc...

Previous studies demonstrated the importance of substrate stiffness and topography on the phenotype of many different cell types including fibroblasts. Yet the interaction of these two physical parameters remains insufficiently characterized, in particular for cardiac fibroblasts. Most studies focusing on contact guidance use rigid patterned substr...

Thymosin β4 (Tβ4) is a peptide with multiple biological functions. Here, we focus on the role of Tβ4 in vascularization, and review our studies of the controlled delivery of Tβ4 through its incorporation in biomaterials. Tβ4 promotes vascularization through VEGF induction and AcSDKP-induced migration and differentiation of endothelial cells. We dev...

We previously reported that preculture of fibroblasts (FBs) and endothelial cells (ECs) prior to cardiomyocytes (CMs) improved the structural and functional properties of engineered cardiac tissue compared to culture of CMs alone or co-culture of all three cell types. However, these approaches did not result in formation of capillary-like cords, wh...

Acute myocardial infarction (MI) leads to fibrosis and severe left ventricular wall thinning. Enhancing vascularization within the infarct reduces cell death and maintains a thick left ventricular wall, which is essential for proper cardiac function. Here, we evaluated the controlled delivery of thymosin β4 (Tβ4), which supports cardiomyocyte survi...

We previously showed that the sequential, but not simultaneous, culture of endothelial cells (ECs), fibroblasts (FBs), and cardiomyocytes (CMs) resulted in elongated, beating cardiac organoids. We hypothesized that the expression of Cx43 and contractile function are mediated by vascular endothelial growth factor (VEGF) released by nonmyocytes durin...

Introduction: Surface topography and electrical field stimulation are important guidance cues that aid the organization and contractility of cardiomyocytes in vivo. We report here on the use of these biomimetic cues in vitro to engineer an implantable contractile cardiac tissue. Methods: Photocrosslinkable collagen-chitosan hydrogels with microg...

The goal of cardiac tissue engineering is to treat cardiovascular diseases through the implantation of engineered functional tissue replacements or the injection of cells and biomaterials, as well as to provide engineered cardiac constructs that can be used as an in vitro model of healthy or diseased heart tissues. This field is rapidly advancing w...

Tissue engineering holds promise in addressing donor organ shortage by combining the knowledge in the fields of cell biology, material science, engineering, and surgery to regenerate or replace injured tissues. Cells, biomaterials, and bioreactors are the three components of the standard tissue-engineering paradigm, and the success in creating func...

Myocardial infarction (MI) results in the death of cardiomyocytes (CM) followed by scar formation and pathological remodeling of the heart. We propose that chitosan conjugated with the angiopoietin-1 derived peptide, QHREDGS, and mixed with collagen I forms a thermoresponsive hydrogel better suited for the survival and maturation of transplanted ca...

Rapid vascularization at the infarcted site is crucial for cardiac repair following myocardial infarction. Thymosin β4 (Tβ4), a 43-amino acid peptide, is both angiogenic and cardioprotective. Tβ4 in soluble form was previously shown to promote cell migration from quiescent adult cardiac explants. Here we developed a collagen-chitosan hydrogel for t...

A key challenge in tissue engineering is overcoming cell death in the scaffold interior due to the limited diffusion of oxygen and nutrients therein. We here hypothesize that immobilizing a gradient of a growth/survival factor from the periphery to the center of a porous scaffold would guide endothelial cells into the interior of the scaffold, thus...

This book chapter will explore the area of cardiac tissue engineering and biomaterials used for cardiac cell therapy. After describing the pathology of heart disease and presenting the motivation for pursuing tissue engineering for the heart, the chapter outlines some of the current clinical treatments used to correct the loss of function resulting...

Rapid vascularization of engineered tissues in vitro and in vivo remains one of the key limitations in tissue engineering. We propose that angiogenic growth factors covalently immobilized on scaffolds for tissue engineering can be used to accomplish this goal. The main objectives of this work were: (a) to derive desirable experimental conditions fo...

Frontispiece: The image shows tube formation by endothelial progenitor cells on collagen scaffolds with co-immobilized vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang1), after 7 days of in vitro cultivation. Representative live/dead images under fluorescence microscopy are shown, where green represents live cells and red represent...

Functional vascularization is a key requirement for the development and function of most tissues, and most critically cardiac muscle. Rapid and irreversible loss of cardiomyocytes during cardiac infarction directly results from the lack of blood supply. Contractile cardiac grafts, engineered using cardiovascular cells in conjunction with biomateria...

Vascularization of engineered tissues in vitro and in vivo remains a key problem in translation of engineered tissues to clinical practice. Growth factor signalling can be prolonged by covalent tethering, thus we hypothesized that covalent immobilization of vascular endothelial growth factor (VEGF-165) to a porous collagen scaffold will enable rapi...

The aim of this study was to engineer a biomaterial capable of supporting vascularization in vitro and in vivo. We covalently immobilized vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang1) onto three-dimensional porous collagen scaffolds using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) chemistry. Over both 3...

The purpose of this study was to design a simple system for cultivation of micro-scale cardiac organoids and investigate the effects of cellular composition on the organoid function. We hypothesized that cultivation of cardiomyocytes (CM) on preformed networks of fibroblasts (FB) and endothelial cells (EC) would enhance the structural and functiona...

Introduction: Cardiovascular diseases have been the main cause of death in Canada for the past 25 years, and accounted for more than 30% of deaths in 20041. Myocardium infarction causes irreversible damage to the heart, and the heart becomes incapable of regeneration due to the non-proliferative nature of terminally differentiated adult cardiomyocy...

The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple ce...

A major challenge in tissue engineering is that functional blood supply is necessary for tissue constructs with thickness greater than 100-200 microns so as to provide sufficient oxygen and nutrients. The aim of this study is to engineer a physiologically interactive replacement consisting functional blood vessels to repair injured cardiovascular t...