Papers by michelle griffin
International journal of biomaterials, 2018
An effective sterilisation technique that maintains structure integrity, mechanical properties, a... more An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide,...
Three-Dimensional Printing Surgical Applications
Eplasty
Three-dimensional printing, a technology used for decades in the industrial field, gains a lot of... more Three-dimensional printing, a technology used for decades in the industrial field, gains a lot of attention in the medical field for its potential benefits. With advancement of desktop printers, this technology is accessible and a lot of research is going on in the medical field. To evaluate its application in surgical field, which may include but not limited to surgical planning, surgical education, implants, and prosthesis, which are the focus of this review. Research was conducted by searching PubMed, Web of science, and other reliable sources. We included original articles and excluded articles based on animals, those more than 10 years old, and those not in English. These articles were evaluated, and relevant studies were included in this review. Three-dimensional printing shows a potential benefit in surgical application. Printed implants were used in patient in a few cases and show successful results; however, longer follow-up and more trials are needed. Surgical and medical education is believed to be more efficient with this technology than the current practice. Printed surgical instrument and surgical planning are also believed to improve with three-dimensional printing. Three-dimensional printing can be a very powerful tool in the near future, which can aid the medical field that is facing a lot of challenges and obstacles. However, despite the reported results, further research on larger samples and analytical measurements should be conducted to ensure this technology's impact on the practice.
Electrical Stimulation Differentiates Adipose Derived Stem Cells (ADSC) to a Neurological Phenotype
Plastic and Reconstructive Surgery, 2015
Eplasty
Objectives: Direct current, capacitive coupling, and inductive coupling are modes of electrical s... more Objectives: Direct current, capacitive coupling, and inductive coupling are modes of electrical stimulation (ES) used to enhance bone healing. It is important to assess the effectiveness of ES for bone healing to ensure optimization for clinical practice. This review aims to examine the level of evidence (LOE) for the application of ES to enhance bone healing and investigate the proposed mechanism for its stimulatory effect. Methods: MEDLINE and EMBASE searches were conducted to identify clinical and in vitro studies utilizing ES for bone healing since 1959. A total of 105 clinical studies and 35 in vitro studies were evaluated. Clinical studies were assigned LOE according to Oxford Centre for Evidence Based Medicine (LOE-1, highest; LOE-5, lowest). Results: Direct current was found to be effective in enhancing bone healing in spinal fusion but only LOE-4 supported its use for nonunions. Eleven studies were retrieved for capacitive coupling with LOE-1 demonstrating its effectiveness...
Acute and Chronic Wound Healing in Diabetic Wounds
Nanoengineering in clinical applications of stem cells
The open orthopaedics journal, 2012
Open lower limb fractures pose a significant challenging pathology for orthopaedic and plastic su... more Open lower limb fractures pose a significant challenging pathology for orthopaedic and plastic surgeons to manage due to the combined soft tissue damage, bone loss and potential vascular compromise. These fracture require extensive team-work and expertise between several surgical specialties and the advice of non-surgical specialties to ensure good clinical outcomes. Extensive research has improved the outcomes of open lower limb fractures and current recommendation on the optimal management is always being updated to enhance patient outcomes. This review serves to provide an overview of the management of open tibial fractures using current evidence and recently updated UK guidelines. The optimal time for surgical debridement, surgical intervention, providing antibiotics and soft tissue coverage will be outlined as well as the indications for amputation.
The open orthopaedics journal, 2012
Compound lower limb fractures pose a significant challenging pathology for orthopaedic and plasti... more Compound lower limb fractures pose a significant challenging pathology for orthopaedic and plastic surgeons to manage due to the combined soft tissue damage, bone injury and potential vascular compromise. These fractures require extensive team-work and expertise between several surgical specialties and the advice of non-surgical specialties, to ensure good clinical outcomes. Extensive research has improved the outcomes of compound lower limb fractures and current recommendation on the optimal management is always being updated to enhance patient outcomes. This review serves to provide an overview of the management of compound tibial fractures using current evidence and recently updated UK guidelines. The optimal time for surgical debridement, surgical intervention, antibiotic regime and soft tissue coverage will be outlined as well as the indications for amputation.
BioTechniques, 2012
Isolation of high-quality RNA from pancreas is challenging because the organ contains large quant... more Isolation of high-quality RNA from pancreas is challenging because the organ contains large quantities of RNases and undergoes autolysis upon harvest. Here we present a simplified perfusion method of the pancreas using an RNase inhibitor. The technique consistently yields high-quality RNA from stored pancreas samples suitable for molecular biology applications, including quantitative RT-PCR. Yields are comparable to RNA isolated from pancreas immediately, but superior to RNA isolated from stored samples that were snap-frozen or immersed in an RNase inhibitor solution. In addition, when compared to the previously reported in situ ductal perfusion technique, our method does not cause histological artifacts.
The open orthopaedics journal, 2011
Mesenchymal stem cells (MSCs) were first discovered by Friedenstein and his colleagues in 1976 fr... more Mesenchymal stem cells (MSCs) were first discovered by Friedenstein and his colleagues in 1976 from bone marrow. The unique property of these cells was their potential to develop into fibroblastic colony forming cells. Since Friedenstein's discovery of these cells the interest in adult MSCs has been progressively growing. Nowadays MSCs are defined as undeveloped biological cells capable of proliferation, self renewal and regenerating tissues. All these properties of MSCs have been discovered in the past 35 years. MSCs can play a crucial role in tissue engineering, organogenesis, gene therapy, transplants as well as tissue injuries. These cells were mainly extracted from bone marrow but there have been additional sources for MSCs discovered in the laboratories including: muscle, dermis, trabecular bone, adipose tissue, periosteum, pericyte, blood, synovial membrane and so forth. The discovery of the alternative sources of MSCs helps widen the application of these cells in differe...
Clinical Science, 2014
Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cy... more Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cystic fibrosis related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared with non-CF. In summary, glycaemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycaemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD.
English
OA Musculoskeletal Medicine, 2013
Toxicologic Pathology, 2009
A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. ... more A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. Five histochemical methods previously reported for eosinophil detection were quantitatively and qualitatively compared in an established murine RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was evaluated in tissue sections of neutrophilic soft tissue lesions and bone marrow from respective animals. Eosinophils had granular red to orange-red cytoplasmic staining, depending on the method, whereas neutrophils had, when stained, a more homogenous cytoplasmic pattern. Nonspecific background staining of similar coloration was variably seen in vascular walls and erythrocytes. Astra Blue/Vital New Red, Congo Red, Luna, Modified Hematoxylin and Eosin, and Sirius Red techniques were all effective in detecting increased eosinophil recruitment compared to controls; however, differences in eosinophil quantification varied significantly between techniques. Astra Blue/Vital New Red had the best specificity for differentiating eosinophils and neutrophils but had a reduced ability to enumerate eosinophils and was the most time intensive. The Luna stain had excessive nonspecific staining of tissues and a reduced enumeration of infiltrating eosinophils, which made it suboptimal. For multiple parameters such as eosinophil detection, specificity, and contrast with background tissues, the Sirius Red followed by Congo Red and Modified Hematoxylin and Eosin methods were useful, each with their own staining qualities.
Exploring the application of mesenchymal stem cells in bone repair and regeneration
The Journal of bone and joint surgery. British volume, 2011
Failure of bone repair is a challenging problem in the management of fractures. There is a limite... more Failure of bone repair is a challenging problem in the management of fractures. There is a limited supply of autologous bone grafts for treating nonunions, with associated morbidity after harvesting. There is need for a better source of cells for repair. Mesenchymal stem cells (MSCs) hold promise for healing of bone because of their capacity to differentiate into osteoblasts and their availability from a wide variety of sources. Our review aims to evaluate the available clinical evidence and recent progress in strategies which attempt to use autologous and heterologous MSCs in clinical practice, including genetically-modified MSCs and those grown on scaffolds. We have compared various procedures for isolating and expanding a sufficient number of MSCs for use in a clinical setting. There are now a number of clinical studies which have shown that implantation of MSCs is an effective, safe and durable method for aiding the repair and regeneration of bone.
Journal of Clinical Investigation, 2010
Animal modeling of this disease has been challenging, with species-and strain-specific difference... more Animal modeling of this disease has been challenging, with species-and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments.
The open orthopaedics journal, 2012
Flexor tendon injuries still remain a challenging condition to manage to ensure optimal outcome f... more Flexor tendon injuries still remain a challenging condition to manage to ensure optimal outcome for the patient. Since the first flexor tendon repair was described by Kirchmayr in 1917, several approaches to flexor tendon injury have enabled successful repairs rates of 70-90%. Primary surgical repair results in better functional outcome compared to secondary repair or tendon graft surgery. Flexor tendon injury repair has been extensively researched and the literature demonstrates successful repair requires minimal gapping at the repair site or interference with tendon vascularity, secure suture knots, smooth junction of tendon end and having sufficient strength for healing. However, the exact surgical approach to achieve success being currently used among surgeons is still controversial. Therefore, this review aims to discuss the results of studies demonstrating the current knowledge regarding the optimal approach for flexor tendon repair. Post-operative rehabilitation for flexor te...
Book and Media Reviews
Addiction Biology, 2003
Radial artery grafts for lower limb revascularisation
PLoS ONE, 2013
Non-unions pose complications in fracture management that can be treated using electrical stimula... more Non-unions pose complications in fracture management that can be treated using electrical stimulation (ES). Bone marrow mesenchymal stem cells (BMMSCs) are essential in fracture healing; however, the effect of different clinical ES waveforms on BMMSCs cellular activities remains unknown. We compared the effects of direct current (DC), capacitive coupling (CC), pulsed electromagnetic field (PEMF) and degenerate wave (DW) on cellular activities including cytotoxicity, proliferation, cell-kinetics and apoptosis by stimulating human-BMMSCs 3 hours a day, up to 5 days. In addition, migration and invasion were assessed using fluorescence microscopy and by quantifying gene and protein expression. We found that DW had the greatest proliferative and least apoptotic and cytotoxic effects compared to other waveforms. DC, DW and CC stimulations resulted in a higher number of cells in S phase and G 2 /M phase as shown by cell cycle analysis. CC and DW caused more cells to invade collagen and showed increased MMP-2 and MT1-MMP expression. DC increased cellular migration in a scratch-wound assay and all ES waveforms enhanced expression of migratory genes with DC having the greatest effect. All ES treated cells showed similar progenitor potential as determined by MSC differentiation assay. All above findings were shown to be statistically significant (p,0.05). We conclude that ES can influence BMMSCs activities, especially DW and CC, which show greater invasion and higher cell proliferation compared to other types of ES. Application of DW or CC to the fracture site may help in the recruitment of BMMSCs to the wound that may enhance rate of bone healing at the fracture site. Citation: Griffin M, Iqbal SA, Sebastian A, Colthurst J, Bayat A (2011) Degenerate Wave and Capacitive Coupling Increase Human MSC Invasion and Proliferation While Reducing Cytotoxicity in an In Vitro Wound Healing Model. PLoS ONE 6(8): e23404.
The open orthopaedics journal, 2011
A bone graft has been the gold standard treatment for repairing bone defects. However, due to bon... more A bone graft has been the gold standard treatment for repairing bone defects. However, due to bone grafts associated donor site morbidity several alternative bone substitutes options have been made available but with their added expense and limited osteoinductive properties they are not ideal. Therefore, research has begun in tissue engineering to investigate stem cells, which are one of the body's own mechanisms used to repair bone. Stem cells are clonogenic undifferentiated cells capable of self-renewal. Readily available from numerous of sources stem cells have the potential to differentiate in osteoblasts and chrondrocytes showing capability to repair both bone and cartilage. The known immunologic properties of stem cells further enhance their therapeutic appeal. Stem cells have shown to be excellent carriers for gene transfer having the capability to be transduced. Gene transfer could enable growth factors and bone morphogentic proteins to enhance bone repair. Stem cells ar...
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Papers by michelle griffin