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Biomedical subjects

Thomas J Webster

Publications and source records attributed to Thomas J Webster.

At least 37 records · Page 2Linked to original sources

Analytically derived material properties of multilaminated extracellular matrix devices using the ball-burst test.

Xenogeneic extracellular matrices (ECMs) have been shown to be effective as naturally occurring scaffolds for soft-tissue repair. As acellular tissue substitutes at the time of surgical implantation, ECMs are subjected to the mechanical forces and micro-environmental conditions representative of the anatomical location in which they are placed. Ideally such natural scaffolds would possess mechanical properties that allow for normal tissue function in and around the implant site. The ball-burst test was used to simulate biaxial forces and to determine the strength of the ECM scaffold under a relevant physiological loading condition. The ball-burst test, in itself, does not quantify intrinsic mechanical properties and therefore a methodology was developed to determine the maximum stress resultant tangent modulus (MSRTM) or the maximum stress tangent modulus (MSTM), stress to failure (sigma(f)), failure stress resultant (N(f)), ball-burst pressure (P), and maximum elongation (lambda(max)) from the raw ball-burst data obtained at a constant-rate of transverse. The analytical methodology was compared to finite element simulations and showed good correlation with the analytical solution presented. The proposed approximations were used to compute biaxial failure properties for a variety of multilaminate ECM devices with varying number of layers, disinfection and sterilization, and organ origin.

Animals↗

Helical rosette nanotubes: a biomimetic coating for orthopedics?

Helical rosette nanotubes (HRN) are obtained through an entropically driven self-assembly process of low-molecular-weight synthetic modules under physiological conditions. Counter-intuitively, these materials undergo extensive self-assembly under the effect of temperature, resulting in networks of very long nanotubes. We have previously shown, using an in vitro model, that titanium (Ti) coated with HRN containing a lysine side chain (HRN-K1) displayed enhanced osteoblast (OB) adhesion when compared to uncoated Ti (p < 0.01). Because it has been widely known that proteins play a critical role in OB adhesion on nanophase materials, here we examine OB adhesion on heated (+T) and unheated (-T) HRN-K1-coated Ti under serum (+S, presence of proteins) and serum-free (-S, absence of proteins) conditions. The results demonstrated that (a) while proteins enhanced OB adhesion on +T HRN-K1-coated Ti, they had no effect on -T HRN-K1-coated Ti, suggesting an active role played by the rosette nanotubes in promoting OB adhesion, and (b) under -S conditions, +T HRN-K1 induced the same level of OB adhesion as uncoated Ti under +S conditions, suggesting that +T HRN-K1 acts as a protein substitute. Finally, transmission electron microscopy and atomic force microscopy studies of +T and -T HRN-K1-coated Ti revealed a significant change in surface coverage, density and hierarchical organization of the nanotubes upon heating, which was correlated with their ability to promote cell adhesion.

Adsorption↗

Nanometer surface roughness increases select osteoblast adhesion on carbon nanofiber compacts.

Carbon nanofibers have exceptional theoretical mechanical properties (such as low weight-to-strength ratios) that, along with possessing nanoscale fiber dimensions similar to crystalline hydroxyapatite found in bone, suggest strong possibilities for use as an orthopedic/dental implant material. To determine, for the first time, cytocompatibility properties pertinent for bone prosthetic applications, osteoblast (bone-forming cells), fibroblast (cells contributing to callus formation and fibrous encapsulation events that result in implant loosening), chondrocyte (cartilage-forming cells), and smooth muscle cell (for comparison purposes) adhesion were determined on carbon nanofibers in the present in vitro study. Results provided evidence that, compared to conventional carbon fibers, nanometer dimension carbon fibers promoted select osteoblast adhesion. Moreover, adhesion of other cells was not influenced by carbon fiber dimensions. In fact, smooth muscle cell, fibroblast, and chondrocyte adhesion decreased with an increase in either carbon nanofiber surface energy or simultaneous change in carbon nanofiber chemistry. To determine properties that selectively enhanced osteoblast adhesion, similar cell adhesion assays were performed on polymer (specifically, poly-lactic-co-glycolic; PLGA) casts of carbon fiber compacts previously tested. Compared to PLGA casts of conventional carbon fibers, results provided the first evidence of enhanced select osteoblast adhesion on PLGA casts of nanophase carbon fibers. The summation of these results demonstrate that due to a high degree of nanometer surface roughness, carbon fibers with nanometer dimensions may be optimal materials to selectively increase osteoblast adhesion necessary for successful orthopedic/dental implant applications.

Alloys↗

Decreased fibroblast cell density on chemically degraded poly-lactic-co-glycolic acid, polyurethane, and polycaprolactone.

Select prolonged functions of fibroblasts leading to extensive fibrous tissue encapsulation can be detrimental to numerous implant applications, including materials designed for the bladder, vasculature, and bone. Specifically, overextended functions of fibroblasts at the tissue-implant interface for orthopedic applications lead to callus formation, fibrous encapsulation events, and ultimately soft (not desirable hard-bony) tissue juxtaposition. Such events result in insufficient regeneration of bone and compromise the overall success of the implant. The objective of the present in vitro study was to determine, for the first time, fibroblast densities on NaOH-treated poly-lactic-co-glycolic acid co-polymers (PLGA), HNO(3)-treated polyurethane (PU), and NaOH-treated polycaprolactone (PCL). Previous studies have demonstrated increased bladder, vascular, and bone cell densities on chemically treated compared to unaltered PLGA, PU, and PCL films. Results of this study provided evidence of decreased fibroblast numbers on chemically treated PLGA, PU, and PCL after time periods of up to 5 days. Examination of these substrates revealed that all chemically modified polymers possessed a high degree of nanometer surface roughness compared to their respective unaltered polymers. In contrast, other material properties (such as chemistry and wettability) were different when comparing chemically treated PLGA, PU, and PCL films. Since fibroblasts are anchorage-dependent cells whose adhesion is a critical prerequisite to the prolonged, extensive formation of a fibrous-tissue containing extracellular matrix, the present in vitro results of decreased fibroblast densities on chemically degraded PLGA, PU, and PCL suggest that these materials may be suitable materials for numerous tissue-engineering applications and, thus, deserve further investigation.

Absorbable Implants↗

Osteoblast response to hydroxyapatite doped with divalent and trivalent cations.

The present in vitro study doped hydroxyapatite (HA) with various metal cations (Mg(2+), Zn(2+), La(3+), Y(3+), In(3+), and Bi(3+)) in an attempt to enhance properties of HA pertinent to orthopedic and dental applications. X-ray diffraction material characterization indicated that the metal cations may have substituted for calcium in the HA crystal structure and that all of the doped HA formulations were single-phase and crystalline. Scanning electron microscopy analysis revealed a variety of grain sizes, depending on the dopant utilized. Energy-dispersive spectroscopy confirmed that the dopants added during synthesis were present and that all of the HA formulations synthesized were within the defined range of HA phase in the CaO-P(2)O(5)-H(2)O system. Lastly, Bi-doped HA had a slower dissolution rate than either undoped HA or HA doped with other cations when exposed to simulated physiological conditions for 21 days. In terms of cell function, results provided the first evidence that osteoblasts, bone-forming cells, adhered and differentiated (as measured by alkaline phosphatase synthesis) in response to HA doped with trivalent cations (specifically, La(3+), Y(3+), In(3+), Bi(3+)) at earlier time points than either HA doped with divalent cations (Mg(2+), Zn(2+)) or undoped HA. Of the dopants examined, Bi(3+) most enhanced osteoblast long-term calcium-containing mineral deposition. For these reasons, this study revealed for the first time the potential benefits of doping HA with Bi(3+) according to criteria critical for bone prosthetic clinical success.

Alkaline Phosphatase↗

Biaxial strength of multilaminated extracellular matrix scaffolds.

Xenogeneic extracellular matrix (ECM) can be harvested and configured to function as a bioscaffold for tissue and organ reconstruction. The mechanical properties of the ECM vary depending upon the tissue from which it is harvested. Likewise, the manufacturing steps required to develop ECMs into medical grade devices will affect the surface morphology and the mechanical properties of the bioscaffold; important properties for constructive tissue remodeling. The present study compared the ball-burst strength of five different ECM scaffolds before and after treatment with peracetic acid (PAA): porcine small intestinal submucosa (SIS), porcine urinary bladder submucosa (UBS), porcine urinary bladder matrix (UBM), a composite of UBS + UBM, and canine stomach submucosa (SS). This study also compared the mechanical properties of 2- and 4-layer ECM scaffolds. Results showed 2-layer SS devices had the highest ball-burst value of all 2-layer ECM devices. Moreover, all 4-layer ECM devices had similar ball-burst strength except for 4-layer UBM devices which was the weakest. PAA-treatment decreased the ball-burst strength of SS and increased the ball-burst strength of UBS 2-layer devices. This study showed the material properties of the ECM scaffolds could be engineered to mimic those of native soft tissues (i.e. vascular, musculotendinous, etc) by varying the number of layers and modifying the disinfection/sterilization treatments used for manufacturing.

Absorbable Implants↗

Increased viable osteoblast density in the presence of nanophase compared to conventional alumina and titania particles.

In the present in vitro study, osteoblast (bone-forming cells) viability and cell density were investigated when cultured in the presence of nanophase compared to conventional (i.e. micron) alumina and titania particles at various concentrations (from 10,000 to 100 microg/ml of cell culture media) for up to 6h. Results confirmed previous studies of the detrimental influences of all ceramic particulates on osteoblast viability and cell densities. For the first time, however, results provided evidence of increased apoptotic cell death when cultured in the presence of conventional compared to nanophase alumina and titania particles. Moreover, since material characterization studies revealed that the only difference between respective ceramic particles was nanometer- and conventional-dimensions (specifically, phase and chemical properties were similar between respective nanophase and conventional alumina as well as titania particles), these results indicated that osteoblast viability and densities were influenced solely by particle size. Such nanometer particulate wear debris may result from friction between articulating components of orthopedic implants composed of novel nanophase ceramic materials. Results of a less detrimental effect of nanometer--as compared to conventional-dimensioned particles on the functions of osteoblasts provide additional evidence that nanophase ceramics may become the next generation of bone prosthetic materials with increased efficacy and, thus, deserve further testing.

Aluminum Oxide↗

Increased osteoblast adhesion on nanophase metals: Ti, Ti6Al4V, and CoCrMo.

Previous studies have demonstrated increased functions of osteoblasts (bone-forming cells) on nanophase compared to conventional ceramics (specifically, alumina, titania, and hydroxyapatite), polymers (such as poly lactic-glycolic acid and polyurethane), carbon nanofibers/nanotubes, and composites thereof. Nanophase materials are unique materials that simulate dimensions of constituent components of bone since they possess particle or grain sizes less than 100 nm. However, to date, interactions of osteoblasts on nanophase compared to conventional metals remain to be elucidated. For this reason, the objective of the present in vitro study was to synthesize, characterize, and evaluate osteoblast adhesion on nanophase metals (specifically, Ti, Ti6Al4V, and CoCrMo alloys). Such metals in conventional form are widely used in orthopedic applications. Results of this study provided the first evidence of increased osteoblast adhesion on nanophase compared to conventional metals. Interestingly, osteoblast adhesion occurred preferentially at surface particle boundaries for both nanophase and conventional metals. Since more particle boundaries are present on the surface of nanophase compared to conventional metals, this may be an explanation for the measured increased osteoblast adhesion. Lastly, material characterization studies revealed that nanometal surfaces possessed similar chemistry and only altered in degree of nanometer surface roughness when compared to their respective conventional counterparts. Because osteoblast adhesion is a necessary prerequisite for subsequent functions (such as deposition of calcium-containing mineral), the present study suggests that nanophase metals should be further considered for orthopedic implant applications.

Alloys↗

Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features.

Biomaterials that successfully integrate into surrounding tissue should match not only the tissue's mechanical properties, but also its topography. The cellular response to a biomaterial may be enhanced in synthetic polymer formulations by mimicking the surface roughness created by the associated nano-structured extra-cellular matrix components of natural tissue. As a first step towards this endeavor, the goal of the present in vitro study was to use these design parameters to develop a synthetic, nano-structured, polymeric biomaterial that promotes cell adhesion and growth for vascular applications. In a novel manner, poly(lactic-co-glycolic acid) (PLGA) (50/50wt% mix) was synthesized to possess a range (from micron to nanometer) of surface features. Reduction of surface features was accomplished by treating conventional PLGA with various concentrations of NaOH for select periods of time. Results from cell experiments indicated that, compared to conventional PLGA, NaOH treated PLGA enhanced vascular smooth muscle cell adhesion and proliferation. However, PLGA prepared by soaking in NaOH decreased endothelial cell adhesion and proliferation compared to conventional PLGA. After further investigation, this finding was determined to be a result of chemical (and not topographical) changes during polymer synthesis. Surface chemistry effects were removed while retaining nano-structured topography by using polymer/elastomer casting methods. Results demonstrated that endothelial and smooth muscle cell densities increased on nano-structured cast PLGA. For these reasons, the present in vitro study provided the first evidence that nano-structured surface features can significantly improve vascular cell densities; such design criteria can be used in the synthesis of the next-generation of more successful tissue-engineered vascular grafts.

Animals↗

Nanobiotechnology: implications for the future of nanotechnology in orthopedic applications.

Nanotechnology involves the use of materials with components, such as fibers, grains and particles, that have dimensions of less than 100 nm. While numerous advantages of nanomaterials have been elucidated for catalytic, processing, mechanical, electrical, and optical applications, few have been described for orthopedic applications. Better orthopedic biomaterials are needed since the average lifetime of a bone biomaterial is less than 15 years. This review discusses recent studies that have been conducted to determine the efficacy of nanophase materials as bone implants. In doing so, it is suggested that nanophase materials can be synthesized to possess similar nanometer dimensions to components of bone tissue to promote new bone formation, compared with conventional orthopedic implant materials.

Biotechnology↗

Technological advances in nanoscale biomaterials: the future of synthetic vascular graft design.

Currently, autologous veins are the first choice for patients in need of bypass grafting materials. However, due to either pre-existing conditions or previous bypass surgery, some patients lack the necessary amount of host tissue for such procedures. Unfortunately, current synthetic vascular grafts of less than 6 mm in diameter have been plagued by a variety of problems. For this reason, there has been significant research aimed at finding more suitable small-diameter vascular graft materials. In order to improve vascular cell functions on such synthetic materials, several techniques are currently under development that attempt to mimic the natural nanometer architecture of the vascular basement membrane. This review presents several processes including colloidal lithography, chemical etching, electrospinning and solid free-form fabrication that could play a role in the future of vascular nanostructured biomaterial development.

Biocompatible Materials↗

Osteoblast function on nanophase alumina materials: Influence of chemistry, phase, and topography.

Alumina is a material that has been used in both dental and orthopedic applications. It is with these uses in mind that osteoblast (bone-forming cell) function on alumina of varying particulate size, chemistry, and phase was tested in order to determine what formulation might be the most beneficial for bone regeneration. Specifically, in vitro osteoblast adhesion, proliferation, intracellular alkaline phosphatase activity, and calcium deposition was observed on delta-phase nanospherical, alpha-phase conventional spherical, and boehmite nanofiber alumina. Results showed for the first time increased osteoblast functions on the nanofiber alumina. Specifically, a 16% increase in osteoblast adhesion over nanophase spherical alumina and a 97% increase over conventional spherical alumina were found for nanofiber alumina after 2 h. A 29% increase in cell number after 5 days and up to a 57% greater amount of calcium was found on the surface of the nanofiber alumina compared with other alumina surfaces. Some of the possible explanations for such enhanced osteoblast behavior on nanofiber alumina may be attributed to chemistry, crystalline phase, and topography. Increased osteoblast function on nanofiber alumina suggests that it may be an ideal material for use in orthopedic and dental applications.

Alkaline Phosphatase↗

Polymers with nano-dimensional surface features enhance bladder smooth muscle cell adhesion.

Previous studies investigating the design of synthetic bladder wall substitutes have involved polymers with micro dimensional structures. Since the body is made up of nano-structured components (e.g., extracellular matrix proteins), the focus of the present in vitro study was to design nano-structured polymers for use as synthetic bladder constructs that mimic the topography of natural bladder tissue. In order to complete this task, novel nano-structured biodegradable polymeric films of poly-lactic-co-glycolic-acid (PLGA), poly-ether-urethane (PU), and poly-caprolactone (PCL) were fabricated and separately treated with various concentrations of NaOH (for PLGA and PCL) and HNO(3) (for PU) for select time periods. These treatments reduced the polymer surface feature dimensions from conventional micron dimensions to biologically inspired nanometer dimensions. Select cytocompatibility properties of these biomaterials were tested in vitro. Results provide the first evidence that adhesion of bladder smooth muscle cells is enhanced as polymer surface feature dimensions are reduced into the nanometer range. In addition, surface analysis results reveal that the polymer nanometer surface roughness is the primary design parameter that increases bladder smooth muscle cell adhesion. For this reason, the "next generation" of tissue-engineered bladder constructs with increased efficacy should contain surfaces with nanometer (as opposed to micron) surface features.

Animals↗

Increased osteoblast adhesion on titanium-coated hydroxylapatite that forms CaTiO3.

CaTiO(3) is a strong candidate to form at the interface between hydroxylapatite (HA) and titanium implants during many coating procedures. However, few studies have compared the cytocompatibility properties of CaTiO(3) to HA pertinent for bone-cell function. For this reason, the objective of the present in vitro study was to determine the ability of bone-forming cells (osteoblasts) to adhere on titanium coated with HA that resulted in the formation of CaTiO(3). To accomplish the formation of CaTiO(3), titanium was coated on HA discs and annealed either under air or a N(2)+H(2) environment. Materials were characterized by X-ray diffraction (XRD), Rutherford backscattering spectroscopy (RBS), and atomic force microscopy (AFM). These characterization techniques demonstrated the formation of a nanometer rough CaTiO(3) layer as a consequence of interactions between HA and titanium during coating conditions. Results from cytocompatibility tests revealed increased osteoblast adhesion on materials that contained CaTiO(3) compared to both pure HA and uncoated titanium. The greatest osteoblast adhesion was observed on titanium-coated HA annealed under air conditions. Because adhesion is a crucial prerequisite to subsequent functions of osteoblasts (such as the deposition of calcium containing mineral), the present in vitro results imply that orthopedic coatings that form CaTiO(3) could increase osseointegration with juxtaposed bone needed for increased implant efficacy.

Animals↗

Selective bone cell adhesion on formulations containing carbon nanofibers.

Bone cell adhesion on novel carbon nanofibers and polycarbonate urethane/carbon nanofiber (PCU/CNF) composites is investigated in the present in vitro study. Carbon nanofibers have exceptional theoretical mechanical properties (such as high strength to weight ratios) that, along with possessing nanoscale fiber dimensions similar to crystalline hydroxyapatite found in physiological bone, suggest strong possibilities for use as an orthopedic/dental implant material. The effects of select properties of carbon fibers (specifically, dimension, surface energy, and chemistry) on osteoblast, fibroblast, chondrocyte, and smooth muscle cell adhesion were determined in the present in vitro study. Results provided evidence that smaller-scale (i.e., nanometer dimension) carbon fibers promoted osteoblast adhesion. Adhesion of other cells was not influenced by carbon fiber dimensions. Also, smooth muscle cell, fibroblast, and chondrocyte adhesion decreased with an increase in either carbon nanofiber surface energy or simultaneous change in carbon nanofiber chemistry. Moreover, greater weight percentages of high surface energy carbon nanofibers in the PCU/CNF composite increased osteoblast adhesion while at the same time decreased fibroblast adhesion.

3T3 Cells↗

Nano-structured polymers enhance bladder smooth muscle cell function.

It is the hypothesis of the present study that a biocompatible material which mimics the nanometer topography of native bladder tissue will enhance cellular responses and lead to better tissue integration in vivo. Previous in vitro studies have verified the ability to successfully reduce the surface feature dimensions of poly(lactic-co-glycolic acid) (PLGA) and poly(ether urethane) (PU) films into the nanometer regime via chemical etching procedures. Results from these studies also provided the first evidence that bladder smooth muscle cell adhesion was enhanced on chemically treated nano-structured polymeric surfaces compared to their conventional counterparts. Although cell adhesion is necessary for a biomaterial's success, subsequent cell functions (such as long-term cell growth and proliferation) are also critical for tissue ingrowth and long-term implant survival. The present in vitro study, therefore, investigated the function of bladder smooth muscle cells on these novel, nano-structured polymers over the expanded periods of 1, 3 and 5 days. Results indicated that cell number was influenced by both surface roughness and surface chemistry changes; the important contributor, however, was increased nanometer surface roughness. This claim is supported by the fact that cell number was enhanced on nano-structured compared to conventional PLGA and PU once chemistry changes were eliminated using casting techniques.

Animals↗

Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. I. Structure and microstructure.

Hydroxylapatite (HA) was made containing magnesium, zinc, cadmium, and yttrium. Salts of these cations were added to precipitating HA; the precipitates were dried and sintered at 1100 degrees C for 1 h. Lattice parameters from X-ray diffraction spectra showed that these elements were incorporated into the apatite structure at a level of 2% added fraction of calcium in HA and up to 7% for yttrium. The densities of different substituted apatites were close to theoretical for pressed and sintered samples, which is evidence for low bulk porosity. The grain sizes of substituted apatites were smaller than those of pure HA except for cadmium-containing apatite. Surfaces of etched samples showed no second phases, whereas surfaces of unetched samples showed second phases and higher porosity than etched surfaces.

Biocompatible Materials↗

Hydroxylapatite with substituted magnesium, zinc, cadmium, and yttrium. II. Mechanisms of osteoblast adhesion.

The present in vitro study investigated osteoblast adhesion on hydroxylapatite (HA) doped with either cadmium (Cd), zinc (Zn), magnesium (Mg), or yttrium (Y). Compared with any other dopant tested in the present study, osteoblast adhesion was significantly (p < 0.05) greater on HA doped with Y after 4 h; in addition, osteoblast adhesion increased with concentration (2-7 mol%) of Y in HA. The findings that HA doped with greater amounts of Y adsorbed higher concentrations of calcium and, subsequently, of vitronectin and collagen (proteins known to mediate osteoblast adhesion), but not of albumin, laminin, and fibronectin, may explain the observed enhanced adhesion of osteoblasts on these substrates. Interactions (i.e., adsorption and configuration/bioactivity) of vitronectin and collagen may have been promoted by increased porosity of doped HA. Through doping with Y, the present study provided the first evidence that HA can be synthesized and processed with improved cytocompatibility properties for osteoblast adhesion, and thus offered essential information for the design of novel proactive bioceramics. Proactive bioceramics which elicit specific, timely, and desired responses from surrounding cells and tissues are necessary for improving bonding of orthopaedic/dental implants to juxtaposed bone; such osseointegration will, undoubtedly, enhance implant efficacy.

Adsorption↗