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Biomedical subjects

Christopher G Williams

Publications and source records attributed to Christopher G Williams.

12 recordsLinked to original sources
PubMed2006

Prognostic significance of microalbuminuria in postdiarrheal hemolytic uremic syndrome.

Patients who survive the acute phase of postdiarrheal hemolytic uremic syndrome (D+ HUS) may develop renal complications after years of apparent recovery. The optimal regimen for monitoring these children is unclear. We therefore determined if screening for microalbuminuria, in the absence of overt proteinuria at follow-up, increased the sensitivity for predicting long-term renal-related sequelae. We found that screening for microalbuminurea, within the first 6-18 months following an episode of HUS, increased the sensitivity for predicting later sequelae from 22 to 66.7%, compared to screening for overt proteinuria alone. These findings, if confirmed by a larger cohort with more years of follow-up, may facilitate early initiation of intervention strategies designed to reduce progressive renal damage.

Adolescent↗
PubMed2005

Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation.

The development of biocompatible photopolymerizing polymers for biomedical and tissue engineering applications has the potential to reduce the invasiveness and cost of biomaterial implants designed to repair or augment tissues. However, more information is needed about the cellular toxicity of the compounds and initiators used in these systems. The current study evaluates the cellular toxicity of three ultraviolet sensitive photoinitiators on six different cell populations that are used for engineering numerous tissues. The photoinitiator 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Irgacure 2959) caused minimal toxicity (cell death) over a broad range of mammalian cell types and species. It was also demonstrated that different cell types have variable responses to identical concentrations of the same photoinitiator. While inherent differences in the cell lines may contribute to the variable cytotoxicity, a correlation between cellular proliferation rate (population doubling time) and increased cytotoxicity of the photoinitiator was observed. Cell lines that divided more quickly were more sensitive to photoinitiator-induced cell death. In summary, the photoinitiator Irgacure 2959 is well tolerated by many cell types over a range of mammalian species. Cell photoencapsulation strategies may be optimized to improve cell survival by manipulating proliferation rate.

Biocompatible Materials↗
PubMed2005

The effect of incorporating RGD adhesive peptide in polyethylene glycol diacrylate hydrogel on osteogenesis of bone marrow stromal cells.

Advances in tissue engineering require biofunctional scaffolds that can not only provide cells with structural support, but also interact with cells in a biological manner. To achieve this goal, a frequently used cell adhesion peptide Arg-Gly-Asp (RGD) was covalently incorporated into poly(ethylene glycol) diacrylate (PEODA) hydrogel and its dosage effect (0.025, 1.25 and 2.5 mm) on osteogenesis of marrow stromal cells in a three-dimensional environment was examined. Expression of bone-related markers, osteocalcin (OCN) and Alkaline phosphatase (ALP), increased significantly as the RGD concentration increased. Compared with no RGD, 2.5 mm RGD group showed a 1344% increase in ALP production and a 277% increase in OCN accumulation in the medium. RGD helped MSCs maintain cbfa-1 expression when shifted from a two-dimensional environment to a three-dimensional environment. Soluble RGD was found to completely block the mineralization of marrow stromal cells, as manifested by quantitative calcium assay, phosphorus elemental analysis and Von Kossa staining. In conclusion, we have demonstrated that RGD-conjugated PEODA hydrogel promotes the osteogenesis of MSCs in a dosage-dependent manner, with 2.5 mm being optimal concentration.

Alkaline Phosphatase↗
PubMed2004

Photocrosslinkable polysaccharides based on chondroitin sulfate.

Photopolymerizing hydrogels have demonstrated potential for use as a scaffold in numerous tissue-engineering applications. The majority of photopolymerizing hydrogels are made from purely synthetic polymers. The purpose of this study was to synthesize and characterize photopolymerizing hydrogels derived from the biopolymer chondroitin sulfate in order to enhance the bioactivity of the scaffold and potentially improve tissue regeneration. Methacrylate groups were added to chondroitin sulfate, a major component of cartilage, using glycidyl methacrylate. The gels exhibited viscoelastic behavior typical of hydrogels. Cogels based on chondroitin sulfate and poly(ethylene glycol) demonstrated increasing pore size with increasing concentration of chondroitin sulfate as determined by water content, mechanical strength, and morphology using scanning electron microscopy. The chondroitin sulfate hydrogels degraded specifically in the presence of the enzyme chondroitinase. Chondrocytes remained viable after photoencapsulation and incubation in the biogels, suggesting their possible use for cartilage tissue engineering.

Animals↗
PubMed2004

Adult stem cell driven genesis of human-shaped articular condyle.

Uniform design of synovial articulations across mammalian species is challenged by their common susceptibility to joint degeneration. The present study was designed to investigate the possibility of creating human-shaped articular condyles by rat bone marrow-derived mesenchymal stem cells (MSCs) encapsulated in a biocompatible poly(ethylene glycol)-based hydrogel. Rat MSCs were harvested, expanded in culture, and treated with either chondrogenic or osteogenic supplements. Rat MSC-derived chondrogenic and osteogenic cells were loaded in hydrogel suspensions in two stratified and yet integrated hydrogel layers that were sequentially photopolymerized in a human condylar mold. Harvested articular condyles from 4-week in vivo implantation demonstrated stratified layers of chondrogenesis and osteogenesis. Parallel in vitro experiments using goat and rat MSCs corroborated in vivo data by demonstrating the expression of chondrogenic and osteogenic markers by biochemical and mRNA analyses. Ex vivo incubated goat MSC-derived chondral constructs contained cartilage-related glycosaminoglycans and collagen. By contrast, goat MSC-derived osteogenic constructs expressed alkaline phosphatase and osteonectin genes, and showed escalating calcium content over time. Rat MSC-derived osteogenic constructs were stiffer than rat MSC-derived chondrogenic constructs upon nanoindentation with atomic force microscopy. These findings may serve as a primitive proof of concept for ultimate tissue-engineered replacement of degenerated articular condyles via a single population of adult mesenchymal stem cells.

Animals↗
PubMed2003

Synthesis and characterization of a novel degradable phosphate-containing hydrogel.

A phosphate-containing and photocrosslinkable polymer, poly(ethylene glycol) di-[ethyl phosphatidyl (ethylene glycol) methacrylate], "PhosPEG-dMA", was synthesized. As a water-soluble macromer, PhosPEG-dMA is suitable for in situ injection and cell-encapsulation by light-induced gelation to produce a novel biocompatible and biodegradable hydrogel for application to cartilage and bone tissue engineering. 1H-NMR, MALDI-TOF mass spectrometry, and elemental analysis were performed to characterize the macromer. Fifteen and 20% (w/v) PhosPEG gels were photopolymerized using UV light with 0.05% photoinitiator. The swelling and water content of the hydrogels was studied and the crosslinking efficiency (density) of the macromers was simulated based on the Peppas-Merrill model. Torsional mechanical analysis of the gels demonstrated a viscoelastic characteristic with high elasticity. The results indicated that, with the fixed PEG-segment size, the greater strength and water-content of the gels depend on the higher crosslinking density. Degradation experiments revealed a linear dry-weight loss of 22.88% and 16.08% from 15% and 20% PhosPEG gels after 9 weeks. The 31P-NMR detected the signals of both phosphate and phosphoric acid in the degrading systems (the gel bulks and the supernatants). Finally, human mesenchymal stem cells (hMSC) were encapsulated into PhosPEG Gel constructs and remained viable as qualitatively demonstrated by "Live/Dead" cell staining assay and MTT assay. The cell-encapsulation efficiency was determined by the characterization of DNA content in each gel construct and the semi-quantitative analysis of the cell viability was also performed by the DNA assay combined with MTT assay.

Acrylates↗
PubMed2003

In vitro chondrogenesis of bone marrow-derived mesenchymal stem cells in a photopolymerizing hydrogel.

Mesenchymal stem cells (MSCs) from skeletally mature goats were encapsulated in a photopolymerizing poly(ethylene glycol)-based hydrogel and cultured with or without transforming growth factor beta1 (TGF) to study the potential for chondrogenesis in a hydrogel scaffold system amenable to minimally invasive implantation. Chondrogenic differentiation was evaluated by histological, biochemical, and RNA analyses for the expression of cartilage extracellular matrix components. The two control groups studied were MSCs cultured in monolayer and MSCs encapsulated in the hydrogel and cultured for 6 weeks in chondrogenic medium without TGF-beta1 (6wk-TGF). The three experimental time points for encapsulated cells studied were 0 days (0d), 3 weeks, and 6 weeks in chondrogenic medium with TGF-beta1 at 10 ng/ml (3wk+TGF and 6wk+TGF). MSCs proliferated in the hydrogels with TGF-beta1. Glycosaminoglycan (GAG) and total collagen content of the hydrogels increased to 3.5% dry weight and 5.0% dry weight, respectively, in 6wk+TGF constructs. Immunohistochemistry revealed the presence of aggrecan, link protein, and type II collagen. Upregulation of aggrecan and type II collagen gene expression compared with monolayer MSCs was demonstrated. Type I collagen gene expression decreased from 3 to 6 weeks in the presence of TGF-beta1. 6wk-TGF hydrogels produced no GAG and only moderate amounts of collagen. However, immunohistochemistry and RT-PCR demonstrated a small amount of spontaneous differentiation in this control group. This study demonstrates the ability to encapsulate MSCs to form cartilage-like tissue in vitro in a photopolymerizing hydrogel. This system may be useful for minimally invasive implantation, MSC differentiation, and engineering of composite tissue structures with multiple cellular phenotypes.

Animals↗
PubMedDate not supplied

A palpable, obstructing carcinoma of the colon incarcerated within a large ventral hernia.

Uncovering the etiology of a bowel obstruction in a patient with a hernia represents a diagnostic dilemma. Although the hernia is often initially the presumptive cause of the bowel obstruction, obstructive carcinoma or another pathological process hidden by the hernia are important considerations. Here we describe a case of a man with an obstructing neoplasm of the colon within a large ventral hernia, whose constipation was initially attributed to incarceration of the hernia.

Aged↗
PubMedDate not supplied

Bioresponsive phosphoester hydrogels for bone tissue engineering.

Bioresponsive and intelligent biomaterials are a vehicle for manipulating cell function to promote tissue development and/or tissue engineering. A photopolymerized hydrogel based on a phosphoester- poly(ethylene glycol) polymer (PhosPEG) was synthesized for application to marrow-derived mesenchymal stem cell (MSC) encapsulation and tissue engineering of bone. The phosphor-containing hydrogels were hydrolytically degradable and the rate of degradation increased in the presence of a bone-derived enzyme, alkaline phosphatase. Gene expression and protein analysis of encapsulated MSCs demonstrated that PhosPEG-PEG cogels containing an intermediate concentration of phosphorus promoted the gene expression of bone-specific markers including type I collagen, alkaline phosphatase, and osteonectin, without the addition of growth factors or other biological agents, compared with pure poly(ethylene glycol)-based gels. Secretion of alkaline phosphatase, osteocalcin, and osteonectin protein was also increased in the PhosPEG cogels. Mineralization of gels increased in the presence of phosphorus in both cellular and acellular constructs compared with PEG gels. In summary, phosphate-PEG-derived hydrogels increase gene expression of bone-specific markers, secretion of bone-related matrix, and mineralization and may have a potential impact on bone-engineering therapies.

Alkaline Phosphatase↗