Jessica Hayes - Academia.edu (original) (raw)

Papers by Jessica Hayes

The field of tissue engineering has expanded at a staggering rate. In terms of bone tissue engine... more The field of tissue engineering has expanded at a staggering rate. In terms of bone tissue engineering research alone this has been represented by a dozen or so manuscripts being published in 1990, increasing to almost 18,000 at the time of writing. This is compounded by the fact that the tissue engineering market is estimated to be approximately 90 billion USD by 2016 [1]. Even so, the leap from research to a reliable commercial product in bone tissue engineering has been slow to say the least, specifically in terms of bioactive materials. This begs the question: What factor(s) are contributing to this evident gap between science and clinics? Does the majority of burden lay with us the scientists? Are clinicians significantly invested in progress? Are the regulatory bodies actively inhibiting progress? Are the industrial targets pulling their weight? And finally, are our funding bodies sufficiently versed in ‘the clinical problem’ to fairly assess true translational medicine? The t...

Training and practice are needed to handle an unusual crisis quickly, safely, and effectively. Fu... more Training and practice are needed to handle an unusual crisis quickly, safely, and effectively. Functional and table-top exercises simulate anticipated CBRNe (Chemical, Biological, Radiological, Nuclear, and Explosive) and public health crises with complex scenarios based on realistic epidemiological, clinical, and biological data from affected populations. For this reason, the use of anonymized databases, such as those from ECDC or NCBI, are necessary to run meaningful exercises. Creating a training scenario requires connecting different datasets that characterise the population groups exposed to the simulated event. This involves interconnecting laboratory, epidemiological, and clinical data, alongside demographic information.The sharing and connection of data among EU member states currently face shortcomings and insufficiencies due to a variety of factors including variations in data collection methods, standardisation practices, legal frameworks, privacy, and security regulation...

Materials science & engineering. C, Materials for biological applications, 2018

Current Stem Cell Research & Therapy, 2015

Long bone fractures in diabetics are slower to heal, have an increased risk for developing non-un... more Long bone fractures in diabetics are slower to heal, have an increased risk for developing non-union and demonstrate greater potential of infection and perioperative complications compared to non-diabetics. The causative aberrant bone mineral density and insufficient bone microstructure of diabetic patients is thought to result from altered osteoblast and osteocyte function, increased bone marrow adiposity, decreased progenitor osteo- and chondral differentiation potential and increased pro-inflammatory cytokine circulation. It is therefore reasonable to hypothesize the root cause of faulty diabetic bone homeostasis and fracture repair is a reduced population of bone marrow progenitor cells and/or their decreased osteochondral capacity complicated by their repressed neo-vascular potential. The potential of transplanted mesenchymal stem cells with a scaffold to support callus formation through the creation of de novo bone in hyperglycemia has been reported. However, there are minimal supporting pre-clinical and clinical investigations confirming these findings. Clinical trials are instead examining mesenchymal stem cell transplantation to slow disease progression, support β-cell viability and function and restore glucose homeostasis while the direct application of allogenic non-diabetic mesenchymal stem cells at the site of orthopaedic injury remains uninvestigated. Here, the literature supporting the application of mesenchymal stem cells in diabetic fracture repair is reviewed including the process of dysfunctional diabetic fracture healing, osteoblast dysregulation and the effect of the hyperglycaemic environment on progenitor cell number and performance with a view to translating the preclinical knowledge base to the administration of mesenchymal stem cells in diabetic fracture repair.

Introduction: Fracture of the tibial and femoral diaphysis constitutes approximately 7% of fractu... more Introduction: Fracture of the tibial and femoral diaphysis constitutes approximately 7% of fractures occurring in children1. Such fractures are commonly repaired by intra-medullary nailing. While removal of implanted nails is often routinely performed after fracture healing it is not always without complication, often due to difficulty or inability to remove the nail.Currently intra-medullary nails are available in either stainless steel or Titanium-Aluminium-Niobium (TAN). TAN is known to have excellent biocompatibility, however, the excellent ability of TAN to promote bone on-growth has been suggested as a cause of the difficulty in removing nails made of this material. Stainless steel nails of a similar design are seldom associated with removal problems from bony integration. Numerous in vitro studies have shown that surface morphology of materials influences osteoblast proliferation, differentiation and phenotype. Work in our group has shown on smooth surfaces such as that of cl...

The Biology and Therapeutic Application of Mesenchymal Cells, 2016

Photons Plus Ultrasound: Imaging and Sensing 2016, 2016

Introduction: The necessity of implant removal, chiefly within the paediatric population is widel... more Introduction: The necessity of implant removal, chiefly within the paediatric population is widely accepted on the grounds of avoiding difficulties such as infection, adverse tissue reaction & the hindrance of bone remodeling 1 . However problems associated with device removal are commonplace & can occur mainly as a result of the complete bony-integration of a device. In clinical terms this is highly undesirable, causing increased operative time & blood loss as well as negatively influencing the healing process. Therefore, we investigated the potential of surface polishing of titanium & its alloys to reduce over-integration of a device from a cellular level, since the surface micro-topography of a material has been shown extensively to be a principle determinant of tissue integration 2 . Methods: Commercially pure titanium (cpTi), Titanium6%Niobium7%Aluminium (TAN), Titanium15%Molybdenum (Ti15Mo) & Stainless steel (Ss, negative control) were studied. Micro- rough standard surfaces o...

The realm of surface-dependent cell and tissue responses is the foundation of orthopaedic-device-... more The realm of surface-dependent cell and tissue responses is the foundation of orthopaedic-device-related research. However, to design materials that elicit specific responses from tissues is a complex proposition mainly because the vast majority of the biological principles controlling the interaction of cells with implants remain largely ambiguous. Nevertheless, many surface properties, such as chemistry and topography, can be manipulated in an effort to selectively control the cell-material interaction. On the basis of this information there has been much research in this area, including studies focusing on the structure and composition of the implant interface, optimization of biological and chemical coatings and elucidation of the mechanisms involved in the subsequent cell-material interactions. Although a wealth of information has emerged, it also advocates the complexity and dynamism of the cell-material interaction. Therefore, this chapter aims to provide the reader with an introduction to the basic concepts of the cell-material interaction and to provide an insight into the factors involved in determining the cell and tissue response to specific surface features, with specific emphasis on surface microtopography.

Journal of biomaterials applications, Jan 15, 2015

A host of research opportunities with innumerable clinical applications are open to biomedical gl... more A host of research opportunities with innumerable clinical applications are open to biomedical glasses if one considers their potential as therapeutic inorganic ion delivery systems. Generally, applications have been limited to repair and regeneration of hard tissues while compositions are largely constrained to the original bioactive glass developed in the 1960s. However, in oncology applications the therapeutic paradigm shifts from repair to targeted destruction. With this in mind, the composition-structure-property-function relationships of vanadium-containing zinc-silicate glasses (0.51SiO2-0.29Na2O-(0.20-X)ZnO-XV2O5, 0 ≤ X ≤ 0.09) were characterized in order to determine their potential as therapeutic inorganic ion delivery systems. Increased V2O5 mole fraction resulted in a linear decrease in density and glass transition temperature (Tg). (29)Si MAS NMR peak maxima shifted upfield while (51)V MAS NMR peak maxima were independent of V2O5 content and overlapped well with the spe...

European cells & materials, 2012

The process of bone formation, remodelling and healing involves a coordinated action of various c... more The process of bone formation, remodelling and healing involves a coordinated action of various cell types. Advances in understanding the biology of osteoblast cells during these processes have been enabled through the use of various in vitro culture models from different origins. In an era of intensive bone tissue engineering research, these cell models are more and more often applied due to limited availability of primary human osteoblast cells. While they are a helpful tool in developing novel therapies or biomaterials; concerns arise regarding their phenotypic state and differences in relation to primary human osteoblast cells. In this review we discuss the osteoblastic development of some of the available cell models; such as primary human, rat, mouse, bovine, ovine and rabbit osteoblast cells; as well as MC3T3-E1, MG-63 and SaOs-2 cell lines, together with their advantages and disadvantages. Through this, we provide suggestions on the selection of the appropriate and most rele...

European cells & materials, 2010

Difficulties removing temporary fracture fixation devices due to excessive bony on-growth results... more Difficulties removing temporary fracture fixation devices due to excessive bony on-growth results in extended surgical time leading to excessive blood loss, debris contamination and potentially refracture. Commercially available locking plates and screws are manufactured for clinics with a micro-rough surface, which contributes to the excessive bony on-growth reported. We have applied polishing technology to commercially pure titanium locking compression plates (LCP) and titanium-6%aluminium-7%niobium (TAN) plates and screws to assess if it can alleviate problems with strong bony overgrowth. Samples were implanted for 6, 12 and 18 months in a bilateral sheep tibia non fracture model and assessed for screw removal torque, percentage of bone contact and tissue-material response. Both electropolishing (p=0.001) and paste polishing (p=0.010) of TAN screws significantly reduced the mean torque required for removal compared to their micro-rough counterparts. This was accompanied by a tren...

European cells & materials, 2009

Fractures of the tibia and femoral diaphysis are commonly repaired by intra-medullary (IM) nailin... more Fractures of the tibia and femoral diaphysis are commonly repaired by intra-medullary (IM) nailing. Currently IM nails are available in either electropolished stainless steel (SS) or in Titanium-Aluminium-Niobium (TAN). After healing, removal of the nails still is common but removal of TAN IM nails often has complications whereas SS IM nails of the same design are less often associated with problems. We believe the differences in removal are due to the ability of TAN to promote strong bone on-growth. We have previously shown in vivo that polishing cortical screws reduces removal torque and the percentage of bone-implant contact. Therefore, we postulate that bony on-growth onto IM nails can be reduced by means of surface polishing, for ease of removal. Here we aim to compare the pull-out forces for removal of standard TAN (TAN-S) compared to experimental paste polished TAN (TAN-PP) IM nails from a bilateral non-fracture sheep tibia model after 12 months implantation. Histological ana...

European cells & materials, 2010

The osteoinductive and conductive capabilities of commercially pure titanium and its alloys is we... more The osteoinductive and conductive capabilities of commercially pure titanium and its alloys is well documented, as is their ability to provide long-term stability for permanent implantable devices. Fracture fixation in paediatric and trauma patients generally requires transient fixation after which the implant becomes redundant and requires removal. Removal can be complicated due to excessive bony over-growth which is encouraged by the standard micro-rough implant surface. We have shown in vivo that removal related morbidity can be significantly reduced with surface polishing, a technique which reduces the micro-roughness of clinically available materials. However, tissue integration at the bone-implant interface requires activation of key regulatory pathways which influences osteoblastic differentiation and maturation therefore we do not believe this effect to be purely mechanical. To elucidate potential mechanisms by which surface polishing exerts its effect on bone regeneration t...

Annals of biomedical engineering, Jan 15, 2015

The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MS... more The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene-terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral defect using a rabbit model. Material characterisation using scanning electron microscopy indicated that the scaffold had a 3D architecture characteristic of the additive manufacturing fabrication method, with a strut diameter of 296 ± 52 μm and a pore size of 512 ± 22 μm × 476 ± 25 μm × 180 ± 30 μm. In vitro optimisation revealed that the scaffold did not generate an adverse cell response, optimal cell loading conditions were achieved using 50 μg/ml fibronectin and a cell seeding density of 25 × 10(6) cells/ml and glycosaminoglycan (GAG) accumulation after 28 days culture in the presence of TGFβ3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted in osteochondral defects for 12 weeks, with cell-free scaffolds and empty defects emp...

The field of tissue engineering has expanded at a staggering rate. In terms of bone tissue engine... more The field of tissue engineering has expanded at a staggering rate. In terms of bone tissue engineering research alone this has been represented by a dozen or so manuscripts being published in 1990, increasing to almost 18,000 at the time of writing. This is compounded by the fact that the tissue engineering market is estimated to be approximately 90 billion USD by 2016 [1]. Even so, the leap from research to a reliable commercial product in bone tissue engineering has been slow to say the least, specifically in terms of bioactive materials. This begs the question: What factor(s) are contributing to this evident gap between science and clinics? Does the majority of burden lay with us the scientists? Are clinicians significantly invested in progress? Are the regulatory bodies actively inhibiting progress? Are the industrial targets pulling their weight? And finally, are our funding bodies sufficiently versed in ‘the clinical problem’ to fairly assess true translational medicine? The t...

Training and practice are needed to handle an unusual crisis quickly, safely, and effectively. Fu... more Training and practice are needed to handle an unusual crisis quickly, safely, and effectively. Functional and table-top exercises simulate anticipated CBRNe (Chemical, Biological, Radiological, Nuclear, and Explosive) and public health crises with complex scenarios based on realistic epidemiological, clinical, and biological data from affected populations. For this reason, the use of anonymized databases, such as those from ECDC or NCBI, are necessary to run meaningful exercises. Creating a training scenario requires connecting different datasets that characterise the population groups exposed to the simulated event. This involves interconnecting laboratory, epidemiological, and clinical data, alongside demographic information.The sharing and connection of data among EU member states currently face shortcomings and insufficiencies due to a variety of factors including variations in data collection methods, standardisation practices, legal frameworks, privacy, and security regulation...

Materials science & engineering. C, Materials for biological applications, 2018

Current Stem Cell Research & Therapy, 2015

Long bone fractures in diabetics are slower to heal, have an increased risk for developing non-un... more Long bone fractures in diabetics are slower to heal, have an increased risk for developing non-union and demonstrate greater potential of infection and perioperative complications compared to non-diabetics. The causative aberrant bone mineral density and insufficient bone microstructure of diabetic patients is thought to result from altered osteoblast and osteocyte function, increased bone marrow adiposity, decreased progenitor osteo- and chondral differentiation potential and increased pro-inflammatory cytokine circulation. It is therefore reasonable to hypothesize the root cause of faulty diabetic bone homeostasis and fracture repair is a reduced population of bone marrow progenitor cells and/or their decreased osteochondral capacity complicated by their repressed neo-vascular potential. The potential of transplanted mesenchymal stem cells with a scaffold to support callus formation through the creation of de novo bone in hyperglycemia has been reported. However, there are minimal supporting pre-clinical and clinical investigations confirming these findings. Clinical trials are instead examining mesenchymal stem cell transplantation to slow disease progression, support β-cell viability and function and restore glucose homeostasis while the direct application of allogenic non-diabetic mesenchymal stem cells at the site of orthopaedic injury remains uninvestigated. Here, the literature supporting the application of mesenchymal stem cells in diabetic fracture repair is reviewed including the process of dysfunctional diabetic fracture healing, osteoblast dysregulation and the effect of the hyperglycaemic environment on progenitor cell number and performance with a view to translating the preclinical knowledge base to the administration of mesenchymal stem cells in diabetic fracture repair.

Introduction: Fracture of the tibial and femoral diaphysis constitutes approximately 7% of fractu... more Introduction: Fracture of the tibial and femoral diaphysis constitutes approximately 7% of fractures occurring in children1. Such fractures are commonly repaired by intra-medullary nailing. While removal of implanted nails is often routinely performed after fracture healing it is not always without complication, often due to difficulty or inability to remove the nail.Currently intra-medullary nails are available in either stainless steel or Titanium-Aluminium-Niobium (TAN). TAN is known to have excellent biocompatibility, however, the excellent ability of TAN to promote bone on-growth has been suggested as a cause of the difficulty in removing nails made of this material. Stainless steel nails of a similar design are seldom associated with removal problems from bony integration. Numerous in vitro studies have shown that surface morphology of materials influences osteoblast proliferation, differentiation and phenotype. Work in our group has shown on smooth surfaces such as that of cl...

The Biology and Therapeutic Application of Mesenchymal Cells, 2016

Photons Plus Ultrasound: Imaging and Sensing 2016, 2016

Introduction: The necessity of implant removal, chiefly within the paediatric population is widel... more Introduction: The necessity of implant removal, chiefly within the paediatric population is widely accepted on the grounds of avoiding difficulties such as infection, adverse tissue reaction & the hindrance of bone remodeling 1 . However problems associated with device removal are commonplace & can occur mainly as a result of the complete bony-integration of a device. In clinical terms this is highly undesirable, causing increased operative time & blood loss as well as negatively influencing the healing process. Therefore, we investigated the potential of surface polishing of titanium & its alloys to reduce over-integration of a device from a cellular level, since the surface micro-topography of a material has been shown extensively to be a principle determinant of tissue integration 2 . Methods: Commercially pure titanium (cpTi), Titanium6%Niobium7%Aluminium (TAN), Titanium15%Molybdenum (Ti15Mo) & Stainless steel (Ss, negative control) were studied. Micro- rough standard surfaces o...

The realm of surface-dependent cell and tissue responses is the foundation of orthopaedic-device-... more The realm of surface-dependent cell and tissue responses is the foundation of orthopaedic-device-related research. However, to design materials that elicit specific responses from tissues is a complex proposition mainly because the vast majority of the biological principles controlling the interaction of cells with implants remain largely ambiguous. Nevertheless, many surface properties, such as chemistry and topography, can be manipulated in an effort to selectively control the cell-material interaction. On the basis of this information there has been much research in this area, including studies focusing on the structure and composition of the implant interface, optimization of biological and chemical coatings and elucidation of the mechanisms involved in the subsequent cell-material interactions. Although a wealth of information has emerged, it also advocates the complexity and dynamism of the cell-material interaction. Therefore, this chapter aims to provide the reader with an introduction to the basic concepts of the cell-material interaction and to provide an insight into the factors involved in determining the cell and tissue response to specific surface features, with specific emphasis on surface microtopography.

Journal of biomaterials applications, Jan 15, 2015

A host of research opportunities with innumerable clinical applications are open to biomedical gl... more A host of research opportunities with innumerable clinical applications are open to biomedical glasses if one considers their potential as therapeutic inorganic ion delivery systems. Generally, applications have been limited to repair and regeneration of hard tissues while compositions are largely constrained to the original bioactive glass developed in the 1960s. However, in oncology applications the therapeutic paradigm shifts from repair to targeted destruction. With this in mind, the composition-structure-property-function relationships of vanadium-containing zinc-silicate glasses (0.51SiO2-0.29Na2O-(0.20-X)ZnO-XV2O5, 0 ≤ X ≤ 0.09) were characterized in order to determine their potential as therapeutic inorganic ion delivery systems. Increased V2O5 mole fraction resulted in a linear decrease in density and glass transition temperature (Tg). (29)Si MAS NMR peak maxima shifted upfield while (51)V MAS NMR peak maxima were independent of V2O5 content and overlapped well with the spe...

European cells & materials, 2012

The process of bone formation, remodelling and healing involves a coordinated action of various c... more The process of bone formation, remodelling and healing involves a coordinated action of various cell types. Advances in understanding the biology of osteoblast cells during these processes have been enabled through the use of various in vitro culture models from different origins. In an era of intensive bone tissue engineering research, these cell models are more and more often applied due to limited availability of primary human osteoblast cells. While they are a helpful tool in developing novel therapies or biomaterials; concerns arise regarding their phenotypic state and differences in relation to primary human osteoblast cells. In this review we discuss the osteoblastic development of some of the available cell models; such as primary human, rat, mouse, bovine, ovine and rabbit osteoblast cells; as well as MC3T3-E1, MG-63 and SaOs-2 cell lines, together with their advantages and disadvantages. Through this, we provide suggestions on the selection of the appropriate and most rele...

European cells & materials, 2010

Difficulties removing temporary fracture fixation devices due to excessive bony on-growth results... more Difficulties removing temporary fracture fixation devices due to excessive bony on-growth results in extended surgical time leading to excessive blood loss, debris contamination and potentially refracture. Commercially available locking plates and screws are manufactured for clinics with a micro-rough surface, which contributes to the excessive bony on-growth reported. We have applied polishing technology to commercially pure titanium locking compression plates (LCP) and titanium-6%aluminium-7%niobium (TAN) plates and screws to assess if it can alleviate problems with strong bony overgrowth. Samples were implanted for 6, 12 and 18 months in a bilateral sheep tibia non fracture model and assessed for screw removal torque, percentage of bone contact and tissue-material response. Both electropolishing (p=0.001) and paste polishing (p=0.010) of TAN screws significantly reduced the mean torque required for removal compared to their micro-rough counterparts. This was accompanied by a tren...

European cells & materials, 2009

Fractures of the tibia and femoral diaphysis are commonly repaired by intra-medullary (IM) nailin... more Fractures of the tibia and femoral diaphysis are commonly repaired by intra-medullary (IM) nailing. Currently IM nails are available in either electropolished stainless steel (SS) or in Titanium-Aluminium-Niobium (TAN). After healing, removal of the nails still is common but removal of TAN IM nails often has complications whereas SS IM nails of the same design are less often associated with problems. We believe the differences in removal are due to the ability of TAN to promote strong bone on-growth. We have previously shown in vivo that polishing cortical screws reduces removal torque and the percentage of bone-implant contact. Therefore, we postulate that bony on-growth onto IM nails can be reduced by means of surface polishing, for ease of removal. Here we aim to compare the pull-out forces for removal of standard TAN (TAN-S) compared to experimental paste polished TAN (TAN-PP) IM nails from a bilateral non-fracture sheep tibia model after 12 months implantation. Histological ana...

European cells & materials, 2010

The osteoinductive and conductive capabilities of commercially pure titanium and its alloys is we... more The osteoinductive and conductive capabilities of commercially pure titanium and its alloys is well documented, as is their ability to provide long-term stability for permanent implantable devices. Fracture fixation in paediatric and trauma patients generally requires transient fixation after which the implant becomes redundant and requires removal. Removal can be complicated due to excessive bony over-growth which is encouraged by the standard micro-rough implant surface. We have shown in vivo that removal related morbidity can be significantly reduced with surface polishing, a technique which reduces the micro-roughness of clinically available materials. However, tissue integration at the bone-implant interface requires activation of key regulatory pathways which influences osteoblastic differentiation and maturation therefore we do not believe this effect to be purely mechanical. To elucidate potential mechanisms by which surface polishing exerts its effect on bone regeneration t...

Annals of biomedical engineering, Jan 15, 2015

The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MS... more The main objective of this study was to evaluate the effectiveness of a mesenchymal stem cell (MSC)-seeded polyethylene-oxide-terephthalate/polybutylene-terephthalate (PEOT/PBT) scaffold for cartilage tissue repair in an osteochondral defect using a rabbit model. Material characterisation using scanning electron microscopy indicated that the scaffold had a 3D architecture characteristic of the additive manufacturing fabrication method, with a strut diameter of 296 ± 52 μm and a pore size of 512 ± 22 μm × 476 ± 25 μm × 180 ± 30 μm. In vitro optimisation revealed that the scaffold did not generate an adverse cell response, optimal cell loading conditions were achieved using 50 μg/ml fibronectin and a cell seeding density of 25 × 10(6) cells/ml and glycosaminoglycan (GAG) accumulation after 28 days culture in the presence of TGFβ3 indicated positive chondrogenesis. Cell-seeded scaffolds were implanted in osteochondral defects for 12 weeks, with cell-free scaffolds and empty defects emp...