Steven Garry Wise

The University of Sydney · School of Medical Sciences

Expanded polytetrafluoroethylene (ePTFE) vascular conduits with less than or equal to 6 mm internal diameter typically occlude due to a combination of thrombus formation and neointimal hyperplasia. We hypothesized that by layering the polymerized elastin precursor, human tropoelastin, in the synthetic vessel lumen we could mimic the internal elasti...

Statement of significance: Tracking the dynamic behaviour of transplanted bone-marrow mononuclear cells (BM-MNCs) is a long-standing research goal. Conventional methods involving contrast and tracer agents interfere with cellular function while also yielding false signals. The use of bioluminescence addresses these shortcomings while allowing for...

Multifunctional nanoparticles are increasingly employed to improve biological efficiency in medical imaging, diagnostics and treatment applications. However, even the most well-established nanoparticle platforms rely on multiple step wet-chemistry approaches for functionalization often with linkers, substantially increasing complexity and cost, whi...

Highlights • Bombyx mori silk was electrospun to engineer mechanically robust vascular grafts that support endothelial cell attachment and monolayer formation while resisting blood adhesion and fibrin assembly in vitro. • Silk grafts were evaluated in a rat aortic interposition grafting model at 3, 6, 12, and 24 weeks. Graft survival for silk graft...

Despite being one of the most clinically trialed cell therapies, bone marrow‐mononuclear cell (BM‐MNC) infusion has largely failed to fulfill its clinical promise. Implanting biomimetic scaffolds at sites of injury prior to BM‐MNC infusion is a promising approach to enhance BM‐MNC engraftment and therapeutic function. Here, it is demonstrated that...

Synthetic vascular grafts are used to bypass significant arterial blockage when native blood vessels are unsuitable, yet their propensity to fail due to poor blood compatibility and progressive graft stenosis remains an intractable challenge. Perlecan is the major heparan sulfate (HS) proteoglycan in the blood vessel wall with an inherent ability t...

Atherosclerosis is the primary cause of cardiovascular disease, resulting in mortality, elevated healthcare costs, diminished productivity, and reduced quality of life for individuals and their communities. This is exacerbated by the limited understanding of its underlying causes and limitations in current therapeutic interventions, highlighting th...

Conventional gas plasma treatments are crucial for functionalizing materials in biomedical applications, but have limitations that hinder their broader use. These methods require exposure to reactive media under vacuum conditions, rendering them unsuitable for substrates that demand aqueous environments, such as proteins and hydrogels. Additionally...

Adverse body reactions to blood-contacting medical devices endanger patient safety and impair device functionality, with events invariably linked to nonspecific protein adsorption due to suboptimal material biocompatibility. To improve the safety and durability of such devices, herein we propose a strategy for introducing stable zwitterionic grafts...

Atherosclerotic plaques are commonly observed at low shear regions, in particular, the left main coronary artery (LMCA) bifurcation. Low shear regions at bifurcations promote endothelial dysfunction, a key factor initiating atherogenesis, however, mechanisms underlying this process are poorly understood. Dynamic in vitro models are critical to inve...

Skin injuries pose significant health challenges, with conditions like burns and diabetic, venous, and pressure ulcers presenting complex wound management scenarios. Effective wound care strategies for these injuries encompass a range of interventions, from simple wound dressings to bioactive materials and surgical procedures involving skin substit...

Extracellular matrix (ECM) stiffening is a common occurrence during the progression of many diseases, such as breast cancer. To accurately mimic the pathophysiological context of disease within 3D in vitro models, there is high demand for smart biomaterials which replicate the dynamic and temporal mechanical cues of diseased states. This study desc...

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflamma...

The use of tissue adhesives dates to 1940s when surgical glues were introduced for wound closure applications. However, current clinically used tissue adhesives (fibrin and cyanoacrylate glues) have limited adhesion strength and biocompatibility issues which restrict their performance in targeted applications. Due to this unmet clinical challenge,...

Covalent biofunctionalization of implant surfaces using anti microbial agents is a promising approach to reducing bone infection and implant failure. Radical‐rich, ion‐assisted plasma polymerized (IPP) coatings enable surface covalent biofunctionalization in a simple manner; but until now, they are limited to only 2D surfaces. Here a new technology...

Medical devices are a mainstay of the healthcare industry, providing clinicians with innovative tools to diagnose, monitor, and treat a range of medical conditions. For implantable devices, it is widely regarded that chronic inflammation during the foreign body response (FBR) is detrimental to device performance, but also required for tissue regene...

The periosteum is a thin layer of connective tissue covering bone. It is an essential component for bone development and fracture healing. There has been considerable research exploring the application of the periosteum in bone regeneration since the 19th century. An increasing number of studies are focusing on periosteal progenitor cells found wit...

MicroRNAs (miRNAs) are increasingly recognised as key regulators of the development and progression of many diseases due to their ability to modulate gene expression post-translationally. While this makes them an attractive therapeutic target, clinical application of miRNA therapy remains at an early stage and in part is limited by the lack of effe...

Models of arterial injury in rodents have been invaluable to our current understanding of vessel restenosis and play a continuing role in the development of endovascular interventions for cardiovascular disease. Mechanical distention of the vessel wall and denudation of the vessel endothelium are the two major modes of vessel injury observed in mos...

Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system...

Introduction: Heart failure due to myocardial infarction is a progressive and debilitating condition, affecting millions worldwide. Novel treatment strategies are desperately needed to minimise cardiomyocyte damage after myocardial infarction and to promote repair and regeneration of the injured heart muscle. Plasma polymerized nanoparticles (PPN)...

Biomimetic scaffolds recreating key elements of the architecture and biological activity of the extracellular matrix have enormous potential for soft tissue engineering applications. Combining appropriate mechanical properties with select biological cues presents a challenge for bioengineering, as natural materials are most bioactive but can lack m...

Minimally invasive interventions using drug-eluting stents or balloons are a first-line treatment for certain occlusive cardiovascular diseases, but the major long-term cause of failure is neointimal hyperplasia (NIH). The drugs eluted from these devices are non-specific anti-proliferative drugs, such as paclitaxel (PTX) or sirolimus (SMS), which d...

Barrier membranes for guided tissue regeneration are essential for bone repair and regeneration. The implanted membranes may trigger early inflammatory responses as a foreign material, which can affect the recruitment and differentiation of bone cells during tissue regeneration. The purpose of this study was to determine whether immobilizing interl...

Hepatocellular carcinoma (HCC) remains a major challenge to clinicians due to its unacceptably high mortality and morbidity. The etiology of HCC is multi-faceted, including viral infection, alcoholism and non-alcoholic fatty liver disease. Dysregulated host immunity contributes to tumorigenesis among these susceptible individuals with pre-existing...

IL-38, an anti-inflammatory cytokine, is a key regulator of homeostasis in host immunity. Intestinal immunity plays a critical role in defence against pathogenic invasion, as it is the largest surface organ and the most common entry point for micro-organisms. Dysregulated IL-38 activity is observed in several autoimmune diseases including systemic...

In vitro models of the vasculature play an important role in biomedical discovery research, with diverse applications in vascular biology, drug discovery and tissue engineering. These models aim to replicate the conditions of the human vasculature including physical geometry, employing appropriate vascular cells exposed to physiological forces. How...

Background: Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality. Aim: To determine whether interleukin (IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients. Method...

BACKGROUND Gastric cancer (GC) is one of the most common malignancies in China with a high morbidity and mortality. AIM To determine whether interleukin (IL)-31, IL-32, and IL-33 can be used as biomarkers for the detection of GC, via evaluating the correlations between their expression and clinicopathological parameters of GC patients. METHODS Tiss...

Endothelial dysfunction, hallmarked by an imbalance between vasoconstriction and vasorelaxation, is associated with diabetes. Thioredoxin Interacting protein (TXNIP), controlled by an exquisitely glucose sensitive gene, is increasingly recognized for its role in diabetes. However, the role of TXNIP in modulating diabetes-related endothelial dysfunc...

Access to lab-grown fully functional blood vessels would provide an invaluable resource to vascular medicine. The complex architecture and cellular makeup of native vessels, however, makes this extremely challenging to reproduce in vitro. Bioreactor systems have helped advanced research in this area by replicating many of the physiological conditio...

Complete and rapid endothelialization is critical to the long-term performance of synthetic vascular grafts. A fully formed endothelium is resistant to thrombosis and mitigates the development of neointimal hyperplasia, the dominant modes of acute and chronic graft failure, respectively. Significant research efforts aim to develop strategies which...

Cardiovascular disease remains the leading cause of death worldwide. Cardiovascular research has therefore never been more crucial. Cardiovascular researchers must be provided with a research environment that enables them to perform at their highest level, maximizing their opportunities to work effectively with key stakeholders to address this glob...

Silk biomaterials are widely used in tissue engineering applications due to their mechanical tuneability, processability and low immunogenic response. However, due to the lack of cell binding sites, further modification is typically required to optimize silk biomaterials towards a specific biomedical application. Plasma immersion ion implantation (...

Background: Recent evidence indicates that high numbers of cardiovascular (CV) researchers have considered leaving the research and academic sector due to lack of job security and low funding success. Thus, there is an urgent need to develop solutions to support the retention of early- and mid-career researchers (EMCRs). Here, we aimed to explore t...

Bioengineering an effective, small diameter (<6 mm) artificial vascular graft for use in bypass surgery when autologous grafts are unavailable remains a persistent challenge. Commercially available grafts are typically made from plastics, which have high strength but lack elasticity and present a foreign surface that triggers undesirable biological...

Surface bio-functionalization through covalent attachment of bioactive molecules is a promising approach to facilitate rapid bone-implant integration. Radical-rich plasma polymer interlayers are highly attractive as platforms that enable covalent biofunctionalization in a single-step, reagent-free manner. However, fabrication of mechanically robust...

Mechanisms involved in the individual susceptibility to atherosclerotic coronary artery disease (CAD) beyond traditional risk factors are poorly understood. Here, we describe the utility of cultured patient-derived endothelial colony-forming cells (ECFCs) in examining novel mechanisms of CAD susceptibility, particularly the role of dysregulated red...

The rising incidence of cardiovascular disease has increased the demand for small diameter (<6 mm) synthetic vascular grafts for use in bypass surgery. Clinically available synthetic grafts (polyethylene terephthalate and expanded polytetrafluorethylene) are incredibly strong, but also highly hydrophobic and inelastic, leading to high rates of fail...

Peripheral artery disease (PAD) has a significant impact on human health, affecting 200 million people globally. Advanced PAD severely diminishes quality of life, affecting mobility, and in its most severe form leads to limb amputation and death. Treatment of PAD is among the least effective of all endovascular procedures in terms of long-term effi...

The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymer...

Encapsulation devices are an emerging barrier technology designed to prevent the immunorejection of replacement cells in regenerative therapies for intractable diseases. However, traditional polymers used in current devices are poor substrates for cell attachment and induce fibrosis upon implantation, impacting long-term therapeutic cell viability....

Background: To determine whether IL-31, IL-32 and IL-33 can be used as biomarkers for the detection of gastric cancer (GC), via evaluating the correlations between IL-31, IL-32 and IL‑33 expression and clinicopathological parameters of GC patients. Methods: Tissue array (n=180) gastric specimens were utilised. IL-31, IL-32 and IL-33 in GC and non-G...

To determine whether IL-31, IL-32 and IL-33 can be used as biomarkers for the detection of gastric cancer (GC), via evaluating the correlations between IL-31, IL-32 and IL‑33 expression and clinicopathological parameters of GC patients. Tissue array (n=180) gastric specimens were utilised. IL-31, IL-32 and IL-33 in GC and non-GC tissues were detect...

Background Cardiovascular disease is the leading cause of death in Australia. Investment in research solutions has been demonstrated to yield health and a 9.8-fold return economic benefit. The sector, however, is severely challenged with success rates of traditional peer-reviewed funding in decline. Here, we aimed to understand the perceived challe...

Multifunctional nanocarriers (MNCs) promise to improve therapeutic outcomes by combining multiple classes of molecules into a single nanostructure, enhancing active targeting of therapeutic agents and facilitating new combination therapies. However, nanocarrier platforms currently approved for clinical use can still only carry a single therapeutic...

The rise of additive manufacturing has provided a paradigm shift in the fabrication of precise, patient-specific implants that replicate the physical properties of native bone. However, eliciting an optimal biological response from such materials for rapid bone integration remains a challenge. Here we propose for the first time a one-step ion-assis...

Endothelial progenitor cells (EPCs) play a key role in neovascularization and have been linked to improved cardiovascular outcomes. Although there is a well-established inverse relationship between androgen levels and cardiovascular mortality in men, the role of androgens in EPC function is not fully understood. In this study, we investigated the e...

Silk fibroin hydrogels crosslinked through di‐tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light‐mediated photoredox system for di‐tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic‐b...

The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold induced FBR. Macrophage colony-stimulating factor (M-CSF), a haematopoietic growth factor, induces macrophages into an M2-like polarized state, leading...

Conventional tough hydrogels offer enhanced mechanical properties and high toughness. Their application scope however is limited by their lack of processability. Here, a new porous tough hydrogel system is introduced which is processable via gel fiber spinning and 3D printing. The tough hydrogels are produced by rehydrating processable organogels d...

Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted...

Application of bio-functionalized coatings on bone implantable devices is a promising approach to direct rapid bone-implant integration. Plasma polymer (PP) films have become increasingly popular as platforms for surface bio-functionalization of implantable devices. However, the production of a reactive, yet stable PP film represents a technologica...

Orthopedic implants are increasing in global prevalence, with hundreds of thousands of operations performed annually. However, a significant proportion of these operations experiences failure due to poor bone integration. Many avenues of investigation have been explored to address this issue and improve the biocompatibility of orthopedic devices by...

Plasma polymerized nanoparticles (PPN) formed in plasma reactors have been considered undesirable in technological applications. More recently however, PPN were proposed as a new class of multifunctional nanocarriers for drug delivery. Therefore, synthesis of PPN requires cost-effective collection strategies that maximize yield and improve reproduc...

There is abundant evidence that low circulating testosterone levels in older men is associated with adverse cardiovascular outcomes, however, the direction of causality is unclear. Although there is a burgeoning interest in the potential of androgen therapy in older men, the effect of androgens on cardiovascular regeneration in aging males remains...

Highlights • Electrospun polycaprolactone surfaces were immobilized with a monolayer of the cytokine interleukin-4 to create a “bioactive” immunomodulatory surface capable of influencing the phenotype of macrophages responding to the material surface in vivo. • Bioactive surfaces, evaluated in vitro by using macrophage culture, exhibited upregulati...

Bone marrow-derived progenitor cell-mediated vasculogenesis is a key process for vascular repair and regeneration. However, the role of androgens in the mechanism of ischemia-induced vasculogenesis remains unclear. In this study, a gender-mismatch murine bone marrow transplant model was used to allow tissue tracking of transplanted cells. Bone marr...

Osseointegration is essential for ensuring optimal functioning and longevity of orthopedic implants. In a significant number of patients, the body does not fully integrate with the orthopedic implant, which opens the potential for the formation of bacterial biofilms and adverse foreign body reactions. Protein-functionalization of the implant surfac...

β3-peptides uniquely form shear thinning hydrogels which are proteolytically stable and biocompatible. Herein we describe the synthesis, material and optical characterization of a new class of fluorescently labelled hydrogelators based on a helical N-acetylated β3-peptide backbone. We have successfully incorporated a fluorophore into the peptide ba...

In the oral cavity, dental implants are exposed to an environment rich in various microbes that can produce infectious biofilms on the implant surface. Here we report the development of two distinct antimicrobial coatings that prevent biofilm formation by fungi or bacteria. The antimicrobial peptides Mel4 and caspofungin were immobilized on titaniu...

Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (IPSCs) have several advantages of other cell...

Elastin is an abundant extracellular matrix protein in elastic tissues, such as arteries, and comprises 30–57% of the aorta by dry mass. The monomeric precursor tropoelastin (TE), undergoes complex processing to form mature elastic fibers. There is abundant evidence for peroxynitrous acid (ONOOH) formation in the inflamed artery wall, and ONOOH-med...

Highlights • This study shows that apoA-I may be an alternative strategy to improve the biocompatibility of stents. • Systemic infusions of apoA-I reduce in-stent neointimal hyperplasia in a murine model of stenting. • The cellular phenotype of the neointima post-stenting is altered by apoA-I infusions such that the smooth muscle cell phenotype is...

Background: Induced pluripotent stem-cell derived endothelial cells (iPSC-ECs) can be generated from any somatic cell and their iPSC sources possess unlimited self-renewal. Previous demonstration of their proangiogenic activity makes them a promising cell type for treatment of ischemic injury. As with many other stem cell approaches, the low rate...

Elastin is an abundant extracellular matrix protein in elastic tissues, including the lungs, skin and arteries, and comprises 30-57% of the aorta by dry mass. The monomeric precursor, tropoelastin (TE), undergoes complex processing during elastogenesis to form mature elastic fibers. Peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent...

Polyurethanes are a diverse class of polymers, with independently tunable mechanical and biodegradation properties making them a versatile platform material for biomedical implants. Previous iterations have failed to adequately embody appropriate mechanical and biological properties, particularly for vascular medicine where strength, compliance and...

We utilised a plasma activated coating (PAC) to covalently bind the active component of high density lipoproteins (HDL), apolipoprotein (apo) A-I, to stainless steel (SS) surfaces. ApoA-I suppresses restenosis and thrombosis and may therefore improve SS stent biocompatibility. PAC-coated SS significantly increased the covalent attachment of apoA-I,...

Current animal models for the evaluation of synthetic grafts are lacking many of the molecular tools and transgenic studies available to other branches of biology. A mouse model of vascular grafting would allow for the study of molecular mechanisms of graft failure, including in the context of clinically relevant disease states. In this study, we c...

Neointima cellularity. Nuclei count of neoinitma using haematoxylin stain. Data expressed as mean ± SEM and the average nuclei count along the length of the graft was analysed using one-way ANOVA, n = 7 animals/timepoint. (TIF)

Contractile smooth muscle cells in neointima. Representative images of cross section with smooth muscle myosin heavy chain 11 stained in red and nucleus in blue. White dotted lines indicate the graft wall. Scale bar = 100 μm. (TIF)