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Biomedical subjects

K M Shakesheff

Publications and source records attributed to K M Shakesheff.

24 records · Page 2Linked to original sources
PubMed2000

Printing patterns of biospecifically-adsorbed protein.

The advancement of elastomeric patterning techniques in recent years has significantly enhanced our ability to spatially control biomaterial surface chemistry at the micrometre level. The application of this technology to the patterning of biomolecules onto solid surfaces has created many potential applications including the development of advanced biosensors, combinatorial library screening and the formation of tissue engineering templates. In this paper, we describe the direct patterning of protein by microcontact printing. An important consideration for the fabrication of protein micropatterns intended for these applications is the nature of the protein immobilization to a substrate. To date, the patterning of proteins by direct microcontact printing (microCP) has relied on the non-covalent adsorption to a substrate. Ideally, the proteins need to be firmly anchored onto a surface without adversely effecting their activity. Here, the high affinity avidin-biotin receptor-ligand interaction has been exploited to form arrays of avidin molecules onto a polymeric substrate expressing biotin moieties. This has created a generic technique by which any biotinylated species can be subsequently immobilized into defined patterns. Utilizing atomic force microscopy (AFM), the patterned surfaces have been characterized to molecular resolution. The micropatterned sample supported cell adhesion when biotin-(G)11-GRGDS was bound to the avidin bearing arrays.

3T3 Cells↗
PubMed1998

A novel biotinylated degradable polymer for cell-interactive applications.

We describe the development of a novel biodegradable polymer designed to present bioactive motifs at the surfaces of materials of any architecture. The polymer is a block copolymer of biotinylated poly(ethylene glycol) (PEG) with poly(lactic acid) (PLA); it utilizes the high-affinity coupling of the biotin-avidin system to undergo postfabrication surface engineering. We show, using surface plasmon resonance analysis (SPR) and confocal microscopy that surface engineering can be achieved under aqueous conditions in short time periods. These surfaces interact with cell surface molecules and generate beneficial responses as demonstrated by the model study of integrin-mediated spreading of endothelial cells on polymer surfaces presenting RGD peptide adhesion sequences.

Animals↗
PubMed1998

The use of SIMS, XPS and in situ AFM to probe the acid catalysed hydrolysis of poly(orthoesters).

Due to poly(orthoesters) being susceptible to acid catalysed hydrolysis, these polymers have attracted considerable interest for the controlled delivery of therapeutic agents within biodegradable matrices. The pH-sensitivity of the poly (orthoesters) has lead to several drug delivery systems being developed, whose rate of drug release is predominantly controlled by the rate of polymer hydrolysis. This study reports on the use of X-ray photoelectron spectroscopy (XPS), secondary ion mass spectrometry (SIMS), and atomic force microscopy (AFM) in a multitechnique approach to probe the effect of acid catalysed hydrolysis at the interface of poly(orthoesters). The molecular specificity of SIMS was successfully employed, suggesting that the preferred mechanism for hydrolysis was via the cleavage of an exocyclic alkoxy bond in the 3,9,-diethylidene-2,4,8,10-tetraoxaspiro [5,5] undecane(DETOSU) unit. The resulting change in the surface chemical structure of the partially hydrolysed poly(orthoester) is such that it was not detectable by XPS analysis. Images acquired from an in situ AFM study of the hydrolysis ofa poly(orthoester), showed changes in the surface morphology, seen as the formation of pits, and an overall thinning of the polymer film. The use of SIMS, XPS and AFM has enabled changes in surface chemistry to be compared with changes in surface morphology. These complementary data, on the behaviour of the polymer during degradation have important implications for the further design of novel biodegradable materials.

Biocompatible Materials↗
PubMed1998

Spatially controlled cell engineering on biodegradable polymer surfaces.

Controlling receptor-mediated interactions between cells and template surfaces is a central principle in many tissue engineering procedures (1-3). Biomaterial surfaces engineered to present cell adhesion ligands undergo integrin-mediated molecular interactions with cells (1, 4, 5), stimulating cell spreading, and differentiation (6-8). This provides a mechanism for mimicking natural cell-to-matrix interactions. Further sophistication in the control of cell interactions can be achieved by fabricating surfaces on which the spatial distribution of ligands is restricted to micron-scale pattern features (9-14). Patterning technology promises to facilitate spatially controlled tissue engineering with applications in the regeneration of highly organized tissues. These new applications require the formation of ligand patterns on biocompatible and biodegradable templates, which control tissue regeneration processes, before removal by metabolism. We have developed a method of generating micron-scale patterns of any biotinylated ligand on the surface of a biodegradable block copolymer, polylactide-poly(ethylene glycol). The technique achieves control of biomolecule deposition with nanometer precision. Spatial control over cell development has been observed when using these templates to culture bovine aortic endothelial cells and PC12 nerve cells. Furthermore, neurite extension on the biodegradable polymer surface is directed by pattern features composed of peptides containing the IKVAV sequence (15, 16), suggesting that directional control over nerve regeneration on biodegradable biomaterials can be achieved.

Animals↗
PubMed1996

The role of scanning probe microscopy in drug delivery research.

The success of a drug delivery system is often dependent on the surface properties of the device. These surface properties will determine the complex dynamic interfacial events that occur when the system is introduced into the aqueous environment of a patient. Development of the scanning probe microscopes has provided a number of very powerful new surface analytical techniques that are making a significant contribution to the characterization of drug delivery systems and the interfacial processes that occur when such systems are exposed to aqueous living environments. In this review, we describe the design and attributes of these instruments and discuss the impact of the techniques on a wide range of drug delivery research. The scanning probe microscopes are providing new insights into important problems concerning drug delivery, including the molecular structure of polymeric biomaterial surfaces, the conformation of target biomolecules, the influence of morphology on biodegradation, the adsorption of proteins to synthetic surfaces, and the structure and interactions of colloidal particles. As the whole field of scanning probe microscopy continues to advance, drug delivery research is set to benefit; in the final section of the review, the future potential derived from the ability to characterize new surface properties under aqueous conditions is discussed.

Drug Delivery Systems↗