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Biomedical subjects

W L Murphy

Publications and source records attributed to W L Murphy.

10 recordsLinked to original sources

Bone regeneration via a mineral substrate and induced angiogenesis.

Angiogenesis and biomineral substrates play major roles in bone development and regeneration. We hypothesized that macroporous scaffolds of biomineralized 85:15 poly(lactide-co-glycolide), which locally release vascular endothelial growth factor-165 (VEGF), would direct simultaneous regeneration of bone and vascular tissue. The presence of a bone-like biomineral substrate significantly increased regeneration of osteoid matrix (32 +/- 7% of total tissue area; mean +/- SD; p < 0.05) and mineralized tissue (14 +/- 2%; P < 0.05) within a rat cranium critical defect compared with a non-mineralized polymer scaffold (19 +/- 8% osteoid and 10 +/- 2% mineralized tissue). Further, the addition of VEGF to a mineralized substrate significantly increased the generation of mineralized tissue (19 +/- 4%; P < 0.05) compared with mineralized substrate alone. This appeared to be due to a significant increase in vascularization throughout VEGF-releasing scaffolds (52 +/- 9 vessels/mm(2); P < 0.05) compared with mineralized scaffolds without VEGF (34 +/- 4 vessels/mm(2)). Surprisingly, there was no significant difference in total osteoid between the two samples, suggesting that increased vascularization enhances mineralized tissue generation, but not necessarily osteoid formation. These results indicate that induced angiogenesis can enhance tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.

Analysis of Variance↗

Polymeric delivery of proteins and plasmid DNA for tissue engineering and gene therapy.

In vivo gene expression can be altered by locally delivered DNA and proteins. The ability to deliver bioactive macromolecules, such as proteins and plasmid DNA, over controllable time frames represents a challenging engineering problem. Considerable success has been achieved with polymeric delivery systems that provide the capability to change cell function either acutely or chronically. This review focuses on controlled delivery of proteins and plasmid DNA from polymers and on the effects of controlled delivery on gene expression, and introduces some cell biological and biochemical parameters to be considered when delivering macromolecules to change cell behavior.

Animals↗

Growth of continuous bonelike mineral within porous poly(lactide-co-glycolide) scaffolds in vitro.

Strategies to engineer bone have focused on the use of natural or synthetic degradable materials as scaffolds for cell transplantation or as substrates to guide bone regeneration. The basic requirements of the scaffold material are biocompatibility, degradability, mechanical integrity, and osteoconductivity. A major design problem is satisfying each of these requirements with a single scaffold material. This study addresses this problem by describing an approach to combine the biocompatibility and degradability of a polymer scaffold with the osteoconductivity and mechanical reinforcement of a bonelike mineral film. We report the nucleation and growth of a continuous carbonated apatite mineral on the interior pore surfaces of a porous, degradable polymer scaffold via a one step, room temperature incubation process. A 3-dimensional, porous scaffold of the copolymer 85:15 poly(lactide-co-glycolide) was fabricated by a solvent casting, particulate leaching process. Fourier transform IR spectroscopy and scanning electron microscopy (SEM) analysis after different incubation times in a simulated body fluid (SBF) demonstrate the growth of a continuous bonelike apatite layer within the pores of the polymer scaffold. Quantification of phosphate on the scaffold displays the growth and development of the mineral film over time with an incorporation of 0.43 mg of phosphate (equivalent to 0.76 mg of hydroxyapatite) per scaffold after 14 days in SBF. The compressive moduli of polymer scaffolds increased fivefold with formation of a mineral film after a 16-day incubation time as compared to control scaffolds. In summary, this biomimetic treatment provides a simple, one step, room temperature method for surface functionalization and subsequent mineral nucleation and growth on biodegradable polymer scaffolds for tissue engineering.

Analysis of Variance↗

Sustained release of vascular endothelial growth factor from mineralized poly(lactide-co-glycolide) scaffolds for tissue engineering.

Strategies to engineer bone tissue have focused on either: (1) the use of scaffolds for osteogenic cell transplantation or as conductive substrates for guided bone regeneration; or (2) release of inductive bioactive factors from these scaffold materials. This study describes an approach to add an inductive component to an osteoconductive scaffold for bone tissue engineering. We report the release of bioactive vascular endothelial growth factor (VEGF) from a mineralized, porous, degradable polymer scaffold. Three dimensional, porous scaffolds of the copolymer 85 : 15 poly(lactide-co-glycolide) were fabricated by including the growth factor into a gas foaming/particulate leaching process. The scaffold was then mineralized via incubation in a simulated body fluid. Growth of a bone-like mineral film on the inner pore surfaces of the porous scaffold is confirmed by mass increase measurements and quantification of phosphate content within scaffolds. Release of 125I-labeled VEGF was tracked over a 15 day period to determine release kinetics from the mineralized scaffolds. Sustained release from the mineralized scaffolds was achieved, and growth of the mineral film had only a minor effect on the release kinetics from the scaffolds. The VEGF released from the mineralized and non-mineralized scaffolds was over 70% active for up to 12 days following mineralization treatment, and the growth of mineral had little effect on total scaffold porosity.

Biocompatible Materials↗

Controlled delivery of inductive proteins, plasmid DNA and cells from tissue engineering matrices.

It has been estimated that half the annual health care budget in the United States is spent on patients suffering from tissue loss and late stage organ failure. Critical limitations inherent in traditional therapies call for novel tissue and organ replacement strategies. This paper discusses development of biomaterials for conductive, inductive and cell-based tissue replacement strategies. Biodegradable polymer scaffolds can be used as space-filling matrices for tissue development and barriers to migration of epithelial cells in tissue conductive approaches. Inductive approaches involve sustained delivery of bioactive factors, such as protein growth factors and DNA, to alter cell function in localized regions. Factors can be released from highly porous polymer scaffolds to allow factor delivery and tissue development to occur in concert. Cell-based approaches involve seeding of cells onto polymeric scaffolds in vitro and subsequent transplantation of the scaffold. New scaffold materials are being developed that address specific tissue engineering design requirements, and in some cases attempt to mimic natural extracellular matrices. These strategies together offer the possibility of predictably forming specific tissue structures, and may provide solutions to problems such as periodontal ligament detachment, alveolar bone resorption and furcation defects.

Absorbable Implants↗

False positive lymphography in Hodgkin's disease: a histologic-lymphadenographic correlation.

A series of 99 consecutive patients having a staging laparotomy for Hodgkin's disease was reviewed. Negative lymph nodes removed during the laparotomy were correlated with lymphograms reported as positive or suspicious. Four patients had large nodes with a prominent hilar area or irregular cortical fat deposits. In two other patients a cluster of small lymph nodes accounted for the radiologic misinterpretation.

Adult↗

Automatic processing quality assurance program: impact on a radiology department.

A method for evaluating processing variability as well as quantitative data on a quality assurance program tested at a radiology department are presented. Thirty per cent of all retakes due to improper overall density could be attributed to processing variation; these could be prevented through a QA program which is highly cost-effective in both monetary and patient-care terms.

Cost-Benefit Analysis↗

Role of 67gallium citrate scanning in the management of non-Hodgkin's lymphoma.

67Gallium scans were performed as part of the initial evaluation in 45 patients with non-Hodgkin's lymphoma. Eighteen of these patients underwent staging laparotomy and splenectomy. In addition, scans were performed either shortly after therapy was completed or during subsequent followup in 10 patients. The initial scans were found most useful for patients with histiocytic lymphoma: in detecting sites of involvement above the diaphragm and the high para-aortic/mesenteric region, and when tumors were greater than 2 cm in diameter. The addition of 67Ga scanning to the pre-operative clinical evaluation reduced the number of incorrectly staged patients from 8 to 4. Reversion of previously positive 67Ga scans to negative in 3 patients with suspected persistent or recurrent disease was associated with fibrosis and no lymphoma when biopsied. Five other patients had histologically documented positive 67Ga scans post-therapy; in 1 the 67Ga scan was only definitive noninvasive procedure. Despite the occurrence of both false-positive and false-negative 67Ga scans, this procedure appears to be a useful supplement to the pretreatment evaluation of patients with non-Hodgkin's lymphoma, especially the histiocytic form. Confirmation of its ability to detect high para-aortic/mesentric involvement may subsequently result in a reduction of the number of staging laparotomies necessary. For the post-treatment followup of these patients 67Ga scans may prove to be valuable noninvasive investigation.

Abdominal Neoplasms↗