
Locke Davenport Huyer- PhD
- PostDoc Position at Dalhousie University
Locke Davenport Huyer
- PhD
- PostDoc Position at Dalhousie University
About
58
Publications
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2,735
Citations
Current institution
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September 2014 - present
Publications
Publications (58)
Itaconate (IA) is an endogenous metabolite and a potent regulator of the innate immune system. It's use in immunomodulatory therapies has faced limitations due to challenges in controlled delivery and requirements of high extracellular concentrations for internalization of the highly polar small molecule to achieve its intracellular therapeutic act...
Non-degradable polymeric implantable medical devices are a mainstay of modern healthcare but can frequently lead to severe complications. These complications are largely attributable to the foreign body response (FBR), which is characterized by excessive inflammation and fibrosis in response to implanted materials. The pathologic mechanisms underpi...
Itaconate (IA) is an endogenous metabolite and a potent regulator of the innate immune system. Its use in immunomodulatory therapies has faced limitations due to inherent challenges in achieving controlled delivery and requirements for high extracellular concentrations to achieve internalization of the highly polar small molecule to achieve its int...
Implantable medical devices (IMDs) collectively represent a critical mainstay in modern medicine. Used in many chronic diseases and in acute surgical interventions, IMDs are often associated with improvements in disease progression, quality of life, and mortality rates. Despite the positive impacts of IMD implementation, excessive fibrosis driven b...
Application of cardiac patches to the heart surface can be undertaken to provide support and facilitate regeneration of the damaged cardiac tissue following ischemic injury. Biomaterial composition is an important consideration in the design of cardiac patch materials as it governs host response to ultimately prevent the undesirable fibrotic respon...
Cardiovascular tissue constructs provide unique design requirements due to their functional responses to substrate mechanical properties and cyclic stretching behavior of cardiac tissue that requires the use of durable elastic materials. Given the diversity of polyester synthesis approaches, an opportunity exists to develop a new class of biocompat...
Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells' (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo-derived senescence signature (SenSig) using a forei...
Background
Tumor resection and subsequent surgical reconstruction is a prevalent, often effective, treatment approach for many operable solid cancers. Unfortunately, post-operative surgical trauma and tissue injury induce major physiological stressors (i.e. acute inflammation and subsequent wound-healing) that can contribute to cancer progression,...
The development of induced-pluripotent stem cell (iPSC)-derived cell types offers promise for basic science, drug testing, disease modeling, personalized medicine, and translatable cell therapies across many tissue types. However, in practice many iPSC-derived cells have presented as immature in physiological function, and despite efforts to recapi...
Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnC) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivoderived senescence signature using a foreign body res...
Senescent cells (SnCs) contribute to normal tissue development and repair but accumulate with aging where they are implicated in a number of pathologies and diseases. Despite their pathological role and therapeutic interest, SnC phenotype and function in vivo remains unclear due to the challenges in identifying and isolating these rare cells. Here,...
B cells are an adaptive immune target of biomaterials development in vaccine research but, despite their role in wound healing, have not been extensively studied in regenerative medicine. To probe the role of B cells in biomaterial scaffold response, we evaluated the B cell response to biomaterial materials implanted in a muscle wound using a biolo...
Owing to their high spatiotemporal precision and adaptability to different host cells, organ-on-a-chip systems are showing great promise in drug discovery, developmental biology studies and disease modeling. However, many current micro-engineered biomimetic systems are limited in technological application because of culture media mixing that does n...
A state-of-the-art organ-on-a-chip system enabled co-culture of highly oxygen-sensitive Faecalibacterium prausnitzii with human intestinal epithelial cells, recapitulating a critical role of the bacteria in the maintenance of anti-inflammatory phenotype of gut epithelium mediated by bacteria-secreted butyrate.
B cells are an adaptive immune target of biomaterials development in vaccine research but despite their role in wound healing have not been studied in tissue engineering and regenerative medicine. We evaluated the B cell response to biomaterial scaffold materials implanted in a muscle wound; a biological extracellular matrix (ECM) and synthetic pol...
Accumulating evidence indicates that air pollution contributes to serious and fatal damage to the cardiovascular system, yet the mechanisms that drive air pollution associated cardiovascular disease and dysfunction remain unclear. In an effort to create a more predictive in vitro model, a 3D platform, known as integrated vasculature for assessing d...
The multi-disciplinary nature of science, technology, engineering, and math (STEM) careers often renders difficulty for high school students navigating from classroom knowledge to post-secondary pursuits. Discrepancies between the knowledge-based high school learning approach and the experiential approach of future studies leaves some students disi...
Itaconate (ITA) is an emerging powerhouse of innate immunity with therapeutic potential that is limited in its ability to be administered in a soluble form. A library of polyester materials that incorporate ITA into polymer backbones resulting in materials with inherent immunoregulatory behavior is developed. Harnessing hydrolytic degradation relea...
In article number 2000046, Milica Radisic and co‐workers design a biomaterial patch that incorporates an adhesive component to improve attachment. To achieve this, a novel polymer is synthesized with elastic properties tailored for cardiac patch applications and enhanced adhesion to tissue. In terms of application, this material is used to fabricat...
In order to secure biomaterials to tissue surfaces, sutures or glues are commonly used. Of interest is the development of a biomaterial patch for applications in tissue engineering and regeneration that incorporates an adhesive component to simplify patch application and ensure sufficient adhesion. A separate region dedicated to fulfilling the spec...
High school science, technology, engineering, and math (STEM) curricula are generally knowledge-based in methodology and focus on content delivery in preparation for post-secondary study. However, the rapid technological change at the cutting edge and the rate of global integration in STEM highlight the importance in developing a holistic critical...
Tumor progression relies on the interaction between neoplastic epithelial cells and their surrounding stromal partners. This cell cross‐talk affects stromal development, and ultimately the heterogeneity impacts drug efficacy. To mimic this evolving paradigm, 3D vascularized pancreatic adenocarcinoma tissue is microengineered in a tri‐culture system...
Biomaterials are becoming increasingly crucial for healthcare solutions, with extensive use in the field of tissue engineering and drug delivery. After implantation, biomaterials trigger an immune response characterized by the recruitment of bone‐marrow‐derived proinflammatory macrophages that develop as the most abundant cell type surrounding the...
Bioelastomers have been extensively used in tissue engineering applications due to favorable mechanical stability, tunable properties and chemical versatility. As these materials generally possess low elastic modulus and relatively long gelation time, it is challenging to 3D print them using traditional techniques. Instead, the field of 3D printing...
The multi-disciplinary nature of science, technology, engineering and math (STEM) careers often renders difficulty for high school students navigating from classroom knowledge to post-secondary pursuits. Discrepancies between the knowledge-based high school learning approach and the experiential approach of undergraduate studies leaves some student...
In article number 1900245 by Milica Radisic and co‐workers, poly(itaconate‐co‐citrate‐co‐octanediol) (PICO) polyester bioelastomers are developed with tunable elasticity and rapid photocrosslinking for soft biomaterial applications. Leveraging a two‐step curing process, PICO materials are moldable into intricate scaffold designs capable of supporti...
Synthetic polyester elastomeric constructs have become increasingly important for a range of healthcare applications, due to tunable soft elastic properties that mimic those of human tissues. A number of these constructs require intricate mechanical design to achieve a tunable material with controllable curing. Here, the synthesis and characterizat...
Currently, the clinic is faced with the difficult task of treating non-healing wounds. While the treatment regimen varies between different patients and wounds, a non-healing wound can be a significant detriment to a patient’s quality of life, thus highlighting the need for more effective treatments. The immune system is heavily involved in regulat...
Myocardial fibrosis is a severe global health problem due to its prevalence in all forms of cardiac diseases and direct role in causing heart failure. The discovery of efficient antifibrotic compounds has been hampered due to the lack of a physiologically relevant disease model. Herein, we present a disease model of human myocardial fibrosis and us...
In article number 1801187 by Milica Radisic, Boyang Zhang, and co‐workers, a scalable, functional, and 96‐well plate compatible platform is presented with innovative multimaterial processing. Three classes of materials are integrated, including built‐in electrodes to drive electrical stimulation for tissue maturation and induce tissue contraction d...
Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing un...
Due to escalating drug developmental costs and limitations of cardiotoxicity screening, there is an urgent need to develop robust in vitro 3D tissue culture platforms that can both facilitate the culture of human cardiac tissues and provide noninvasive functional readouts predictive of cardiotoxicity in clinical settings. However, such platforms co...
Microengineered biomimetic systems for organ-on-a-chip or tissue engineering purposes often fail as a result of an inability to recapitulate the in vivo environment, specifically the presence of a well-defined vascular system. To address this limitation, we developed an alternative method to cultivate three-dimensional (3D) tissues by incorporating...
Senior high school students often struggle with recognizing the link between human health care and engineering, resulting in limited recruitment for post-secondary biomedical engineering (BME) study. To enhance student comprehension and recruitment in the field, BME graduate student instructors have developed and launched Discovery, a collaborative...
Wound healing is a highly complex process of tissue repair that relies on the synergistic effect of a number of different cells, cytokines, enzymes, and growth factors. A deregulation in this process can lead to the formation of a non-healing chronic ulcer. Current treatment options, such as collagen wound dressings, are unable to meet the demand s...
– With the diverse nature of the biomedical engineering (BME) field, high school students are often limited in their understanding of the area during consideration for post-secondary study. In effort to improve student comprehension, as well as provide a unique learning opportunity in STEM (science, technology, engineering, and math) curriculum, gr...
Using the methods described herein, we have demonstrated how scaffolds can be designed for a number of applications including tissue engineering, biomedical devices and injectable tissues. Details on the methods of polymerization, physical and chemical characterization of poly(octamethylene maleate (anhydride) citrate (POMaC) are described. Two POM...
In article 1703524, Milica Radisic, Boyang Zhang, and co-workers present a user-friendly 96-well plate platform (InVADE, Integrated Vasculature for Assessing Dynamic Events) that utilizes a single vascularized scaffold to replicate in vivo like drug transfer and cell trafficking between multiple organs. Offering highly reproducible in vivo simulati...
Drug screening with simplified 2D cell culture and relevant animal testing fail to
predict clinical outcomes. With the rising cost of drug development, predictive
3D tissue models with human cells are in urgent demand. Establishing vascular
perfusion of 3D tissues has always been a challenge, but it is necessary to
mimic drug transport and to captu...
Significant advances in biomaterials, stem cell biology, and microscale technologies have enabled the fabrication of biologically relevant tissues and organs. Such tissues and organs, referred to as organ-on-a-chip (OOC) platforms, have emerged as a powerful tool in tissue analysis and disease modeling for biological and pharmacological application...
Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection...
Statement of significance:
Achieving a high elasticity and a high conductivity in a single cardiac tissue engineering material remains a challenge. We report the use of CNTs in making electrically conductive and mechanically strong polymeric scaffolds in cardiac tissue regeneration. CNTs were incorporated in elastomeric polymers in a facile and re...
Polyester biomaterials are used in tissue engineering as scaffolds for implantation of tissues developed in vitro. An ideal biodegradable elastomer for cardiac tissue engineering exhibits a relatively low Young’s modulus, with high elongation and tensile strength. Here we describe a novel polyester biomaterial that exhibits improved elastic propert...
Engineering mature tissues requires a guided assembly of cells into organized three-dimensional (3D) structures with multiple cell types. Guidance is usually achieved by microtopographical scaffold cues or by cell-gel compaction. The assembly of individual units into functional 3D tissues is often time-consuming, relying on cell ingrowth and matrix...
Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac tissue engineering is the...