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Geoffrey W Stevens

Publications and source records attributed to Geoffrey W Stevens.

11 recordsLinked to original sources
PubMed2007

The role of biological extracellular matrix scaffolds in vascularized three-dimensional tissue growth in vivo.

An in vivo murine vascularized chamber model has been shown to generate spontaneous angiogenesis and new tissue formation. This experiment aimed to assess the effects of common biological scaffolds on tissue growth in this model. Either laminin-1, type I collagen, fibrin glue, hyaluronan, or sea sponge was inserted into silicone chambers containing the epigastric artery and vein, one end was sealed with adipose tissue and the other with bone wax, then incubated subcutaneously. After 2, 4, or 6 weeks, tissue from chambers containing collagen I, fibrin glue, hyaluronan, or no added scaffold (control) had small amounts of vascularized connective tissue. Chambers containing sea sponge had moderate connective tissue growth together with a mild "foreign body" inflammatory response. Chambers containing laminin-1, at a concentration 10-fold lower than its concentration in Matrigel, resulted in a moderate adipogenic response. In summary, (1) biological hydrogels are resorbed and gradually replaced by vascularized connective tissue; (2) sponge-like matrices with large pores support connective tissue growth within the pores and become encapsulated with granulation tissue; (3) laminin-containing scaffolds facilitate adipogenesis. It is concluded that the nature and chemical composition of the scaffold exerts a significant influence on the amount and type of tissue generated in this in vivo chamber model.

Absorbable Implants↗
PubMed2006

Dynamic forces between two deformable oil droplets in water.

The understanding of static interactions in colloidal suspensions is well established, whereas dynamic interactions more relevant to biological and other suspended soft-matter systems are less well understood. We present the direct force measurement and quantitative theoretical description for dynamic forces for liquid droplets in another immiscible fluid. Analysis of this system demonstrates the strong link between interfacial deformation, static surface forces, and hydrodynamic drainage, which govern dynamic droplet-droplet interactions over the length scale of nanometers and over the time scales of Brownian collisions. The results and analysis have direct bearing on the control and manipulation of suspended droplets in soft-matter systems ranging from the emulsions in shampoo to cellular interactions.

Journal Article↗
PubMed2006

A blank slate? Layer-by-layer deposition of hyaluronic acid and chitosan onto various surfaces.

Although poly(alpha-hydroxy esters), especially the PLGA family of lactic acid/glycolic acid copolymers, have many properties which make them promising materials for tissue engineering, the inherent chemistry of surfaces made from these particular polymers is problematic. In vivo, they promote a strong foreign-body response as a result of nonspecific adsorption and denaturation of serum proteins, which generally results in the formation of a nonfunctional fibrous capsule. Surface modification post-production of the scaffolds is an often-utilized approach to solving this problem, conceptually allowing the formation of a scaffold with mechanical properties defined by the bulk material and molecular-level interactions defined by the modified surface properties. A promising concept is the so-called "blank slate": essentially a surface that is rendered resistant to nonspecific protein adsorption but can be readily activated to covalently bind bio-functional molecules such as extracellular matrix proteins, growth factors or polysaccharides. This study focuses on the use of the quartz crystal microbalance (QCM) to follow the layer-by-layer (LbL) electrostatic deposition of high molecular weight hyaluronic acid and chitosan onto PLGA surfaces rendered positively charged by aminolysis, to form a robust, protein-resistant coating. We further show that this surface may be further functionalized via the covalent attachment of collagen IV, which may then be used as a template for the self-assembly of basement membrane components from dilute Matrigel. The response of NIH-3T3 fibroblasts to these surfaces was also followed and shown to closely parallel the results observed in the QCM.

3T3 Cells↗
PubMed2006

Systematic selection of solvents for the fabrication of 3D combined macro- and microporous polymeric scaffolds for soft tissue engineering.

In this study, we investigate the fabrication of 3D porous poly(lactic-co-glycolic acid) (PLGA) scaffolds using the thermally-induced phase separation technique. The current study focuses on the selection of alternative solvents for this process using a number of criteria, including predicted solubility, toxicity, removability and processability. Solvents were removed via either vacuum freeze-drying or leaching, depending on their physical properties. The residual solvent was tested using gas chromatography-mass spectrometry. A large range of porous, highly interconnected scaffold architectures with tunable pore size and alignment was obtained, including combined macro- and microporous structures and an entirely novel 'porous-fibre' structure. The morphological features of the most promising poly(lactic-co-glycolic acid) scaffolds were analysed via scanning electron microscopy and X-ray micro-computed tomography in both two and three dimensions. The Young's moduli of the scaffolds under conditions of temperature, pH and ionic strength similar to those found in the body were tested and were found to be highly dependent on the architectures.

Biocompatible Materials↗
PubMed2005

Postsynthesis vapor-phase functionalization of MCM-48 with hexamethyldisilazane and 3-aminopropyldimethylethoxylsilane for bioseparation applications.

MCM-48 was surface modified via vapor-phase reactions with hexamethyldisilazane (CH(3)-MCM-48) and 3-aminopropyldimethylethoxysilane (NH(2)-MCM-48). (29)Si NMR confirmed that the resulting materials contained covalently attached trimethylsilane and 3-aminopropyldimethylsilane moieties, both important functionalities for bioseparation applications. The surface coverage was approximately 1.8 and 0.9 groups per nm(2), respectively. The X-ray diffraction patterns and the narrow pore size distributions obtained from the gas sorption isotherms showed that the modified materials retained the characteristic pore structure of the underlying MCM-48 material. CH(3)-MCM-48 exhibited significantly improved hydrolytic stability over the unmodified MCM-48 under the aqueous conditions tested, whereas NH(2)-MCM-48 appeared to be less stable than the unmodified MCM-48. The decrease in stability is most likely due to the nature of the attachment of the 3-aminopropyldimethylsilane moiety, where the conversion of surface silanol groups is limited by H bonding with the amino end, leading to a 50% lower surface concentration and resulting in an increased likelihood of nucleophilic attack on the silica surface, enhancing the rate of hydrolysis. Hexamethyldisilazane thus appears to be a superior functional group for modifying the MCM-48 surface.

Indicators and Reagents↗
PubMed2005

Interaction forces between oil-water particle interfaces--non-DLVO forces.

The interaction force between a rigid silica sphere and a butyl or octyl acetate droplet was measured in an aqueous environment using atomic force microscopy (AFM). The force measurements were performed without added stabilizers and the observed force behavior was found to be dependent on the type of inorganic electrolyte present, where the interfacial tension was constant over the electrolyte concentration range used. Force measurements in the presence of sodium nitrate showed repulsion at all concentrations. Force measurements in the presence of calcium nitrate or sodium perchlorate exhibited an initial repulsion followed by an attraction resulting in a mechanical instability in the AFM cantilever, termed jump-in. The force behavior observed was independent of the water solubility of the organic liquid, in that the same force-distance characteristics were obtained for slightly water soluble butyl acetate and the water sparingly soluble octyl acetate droplets. Modeling of the drop profile during particle-droplet interactions for this type of AFM measurement showed that the force-distance data for the sodium nitrate system obeys typical DLVO interactions. The disagreement between the DLVO predictions for the sodium perchlorate and calcium nitrate systems is attributed to a specific ion effect at the liquid-liquid interface, which gives rise to an attraction force that is greater than the electrostatic double layer repulsion over the length scale of 5 to 10 nm.

Journal Article↗
PubMed2004

Architecture control of three-dimensional polymeric scaffolds for soft tissue engineering. I. Establishment and validation of numerical models.

One of the most important functions of artificial three-dimensional (3D) polymeric scaffolds is to serve as a physical support to provide tissues with an appropriate architecture for in vitro cell culture as well as in vivo tissue regeneration. The production of three-dimensional (3D) polymeric scaffolds with tailored macroporous architecture is thus a crucial step in promoting controlled vascularization and tissue growth within host environments. In this study, 3D poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by a thermally induced phase-separation (TIPS) technique. By controlling the quenching strategy, 3D interconnected PLGA scaffolds with tunable pore size and alignment were obtained and characterized with the use of scanning electron microscopy (SEM). A series of numerical heat-transfer models were established in an effort to describe the cooling process within the PLGA freezing regime. Among them, a two-dimensional (2D) solidification model has proved to be the most successful in describing the quenching of the polymer solution and has the potential to be used to infer the various 3D macroporous architectures created from different quenching conditions.

Biocompatible Materials↗
PubMed2004

Forces between two oil drops in aqueous solution measured by AFM.

The surface and hydrodynamic forces between individual oil droplets in solution can provide insight into both emulsion stability and processes such as drop coalescence in liquid-liquid extraction. We present the first measurements of the interaction forces between alkane droplets in aqueous solution using atomic force microscopy. The radii of the droplets were well below the capillary lengths for the system, thus gravity effects are negligible, and interfacial tension and interaction forces governed the system behavior. The effects of modulating electrostatic double-layer interactions and interfacial tension through the presence of an anionic surfactant are demonstrated. Challenges in interpretation of the force data due to drop deformation are also discussed. A range of drop approach and retract speeds was used to determine the regime where hydrodynamic drainage effects had significant impact on the measurement.

Letter↗
PubMed2004

New murine model of spontaneous autologous tissue engineering, combining an arteriovenous pedicle with matrix materials.

The authors previously described a model of tissue engineering in rats that involves the insertion of a vascular pedicle and matrix material into a semirigid closed chamber, which is buried subcutaneously. The purpose of this study was to develop a comparable model in mice, which could enable genetic mutants to be used to more extensively study the mechanisms of the angiogenesis, matrix production, and cellular migration and differentiation that occur in these models. A model that involves placing a split silicone tube around blood vessels in the mouse groin was developed and was demonstrated to successfully induce the formation of new vascularized tissue. Two vessel configurations, namely, a flow-through pedicle (n = 18 for three time points) and a ligated vascular pedicle (n = 18), were compared. The suitability of chambers constructed from either polycarbonate or silicone and the effects of incorporating either Matrigel equivalent (n = 18) or poly(DL-lactic-co-glycolic acid) (n = 18) on angiogenesis and tissue production were also tested. Empty chambers, chambers with vessels only, and chambers with matrix only served as control chambers. The results demonstrated that a flow-through type of vascular pedicle, rather than a ligated pedicle, was more reliable in terms of patency, angiogenesis, and tissue production, as were silicone chambers, compared with polycarbonate chambers. Marked angiogenesis occurred with both types of extracellular matrix scaffolds, and there was evidence that native cells could migrate into and survive within the added matrix, generating a vascularized three-dimensional construct. When Matrigel was used as the matrix, the chambers filled with adipose tissue, creating a highly vascularized fat flap. In some cases, new breast-like acini and duct tissue appeared within the fat. When poly(dl-lactic-co-glycolic acid) was used, the chambers filled with granulation and fibrous tissue but no fat or breast tissue was observed. No significant amount of tissue was generated in the control chambers. Operative times were short (25 minutes), and two chambers could be inserted into each mouse. In summary, the authors have developed an in vivo murine model for studying angiogenesis and tissue-engineering applications that is technically simple and quick to establish, has a high patency rate, and is well tolerated by the animals.

Animals↗
PubMedDate not supplied

Controllable surface modification of poly(lactic-co-glycolic acid) (PLGA) by hydrolysis or aminolysis I: physical, chemical, and theoretical aspects.

While biodegradable, biocompatible polyesters such as poly (lactic-co-glycolic acid) (PLGA) are popular materials for the manufacture of tissue engineering scaffolds, their surface properties are not particularly suitable for directed tissue growth. Although a number of approaches to chemically modify the PLGA surface have been reported, their applicability to soft tissue scaffolds, which combine large volumes, complex shapes, and extremely fine structures, is questionable. In this paper, we describe two wet-chemical methods, base hydrolysis and aminolysis, to introduce useful levels of carboxylic acid or primary and secondary amine groups, respectively, onto the surface of PLGA with minimal degradation. The effects of temperature, concentration, pH, and solvent type on the kinetics of these reactions are studied by following changes in the wettability of the PLGA using contact angle measurements. In addition, the treated surfaces are studied using X-ray photoelectron spectroscopy (XPS) to determine the effect on the surface chemical structure. Furthermore, we show using XPS analysis that these carboxyl and amine groups are readily activated to allow the covalent attachment of biological macromolecules.

Amines↗