Biomedical subjects

Jöns Hilborn

Publications and source records attributed to Jöns Hilborn.

14 recordsLinked to original sources

PubMed2007

Protein adsorption onto polyester surfaces: is there a need for surface activation?

Surface hydrolysis of polyester scaffolds is a convenient technique suggested to promote protein adsorption for improving cell attachment. We have, therefore, investigated the effect of hydrolysis of polyester surfaces for protein adsorption to clarify the conditions needed. Three polyesters, poly(ethylene terephthalate) (PET), poly(lactic acid) (PLA), and poly(glycolic acid) (PGA), were selected. Adsorption was investigated by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and quartz crystal microbalance (QCM). Hydrolyzed PET adsorbed significantly more proteins than nonhydrolyzed. Degradable polymers adsorbed at higher rates when the polymers were hydrolyzed prior to adsorption, but the same amount as nonhydrolyzed, suggesting spontaneous hydrolysis during the adsorption. XPS shows that hydrolysis prior to absorption for PET results in a surface nitrogen composition of approximately 14%, similar to pure protein (16%). Nonhydrolyzed PET surfaces showed only approximately 7% nitrogen, indicating protein layers thinner than approximately 10 nm. Adsorption to PLA and PGA shows nitrogen contents of 14-15% in both cases. SEM revealed striking differences in morphology of the protein coating. Hydrolyzed or spontaneously hydrolyzable surfaces display a pronounced fibrous structure while nonhydrolyzed surfaces give smooth structures. In combination, the results show that surface hydrolysis increase adsorption rate, but not the amount of proteins on polyesters that degrades in vivo. Surface treatment of nondegradable polyester increases the total amount of proteins and induces the formation of fibrous protein structures. Post hydrolysis treatment by acetic acid, replacing the counter-ion to a proton, further enhances protein attachment. Finally, cell attachment experiments verifies that protein adsorption increase the cell attachment to polyester surfaces.

3T3 Cells↗

PubMed2006

Photoelectron spectroscopy studies of the functionalization of a silicon surface with a phosphorylcholine-terminated polymer grafted onto (3-aminopropyl)trimethoxysilane.

The structure of a biomimetic phosphorylcholine (PC)-functionalized poly(trimethylene carbonate) (PC-PTMC-PC), linked to a silicon substrate through an aminolysis reaction at 120 degrees C with (3-aminopropyl)trimethoxysilane (APTMS), was studied using photoelectron spectroscopy. Two chemical states were found for the unreacted APTMS amine, a neutral state and a protonated state, where the protonated amine on average was situated closer to the silicon substrate than the neutral amine. The experiments also indicated the presence of a third chemical state, where amines interact with unreacted silanol groups. The PTMC chains of the grafted films were found to consist of only 2-3 repeat units, with the grafted chains enriched in the zwitterionic end group, suggesting that these groups are attracted to the surface. This was further supported by the experiments showing that the PC groups were situated deeper within the film.

Electrons↗

PubMed2006

Synthetic biodegradable ionomers that engulf, store, and deliver intact proteins.

Telechelic anionic and cationic biodegradable ionomers capable of loading, storing, and releasing proteins are presented. Two different ionomers have been synthesized with either anionic or cationic end groups. The reaction was done quantitatively as shown by (1)H NMR. The swelling properties of the hydrophobic poly(trimethylene carbonate) polymer are contributed to the ionic end groups that display hydrophilic properties. Depending on the molecular weight of the ionomer, and also on the ionic charge, the materials swell differently in water, from approximately 50% for M(w) = 12 000 g/mol to approximately 500% when dealing with 2000 g/mol. The high swelling led us to believe that it would be possible to load and release proteins preferably in a still active form. As models, two different proteins were chosen: hemoglobin and cytochrome c. The swelling and release study shows that both ionomers possess the capability to adsorb and later release the proteins with retained structure. Release measurements from both the swollen and dried states have been evaluated with similar results, showing that the dried state seems to release a little bit less than the swollen one. These kinds of materials should be interesting for a wide variety of applications where drug and protein release is wanted, as well as in applications such as protein separation media.

Adsorption↗

PubMed2006

Three-dimensional technology and bone morphogenetic protein in frontal bone reconstruction.

Osteoinductive bone morphogenetic proteins (BMPs) may be used in humans to facilitate healing of bony defects. The effect of different BMPs is, as with many other growth factors, highly dependent on the delivery vehicle. Bovine type I collagen is currently used in the clinical setting as a carrier and has been approved in several countries for human use. Here, we report the reconstruction of a frontal bone defect using heparin together with bovine type I collagen, hyaluronic acid, and fibrin as vehicles for BMP-2. A bony structure was created on the back of the patient by treating the latissimus dorsi muscle with the growth factor. A polyamide mold was used as a template to achieve the desired shape. The bone structure was transplanted into the defect site via microsurgical techniques. Although the prefabricated bone was not large enough tocover the entire frontal defect, the reconstruction was completed by using an additional cranial implant.

Animals↗

PubMed2006

Biocompatible and biodegradable phosphorylcholine ionomers with reduced protein adsorption and cell adhesion.

In this paper a recently developed biodegradable phosphorylcholine ionomer (PC ionomer) was evaluated in different biological environments with a focus on the adsorption of proteins (fibrinogen) and the adhesion of cells. Our results have shown that the polar phosphoryl choline (PC) group may be enriched at the surface of cast films with an added hydrophilic environment. X-ray photoelectron spectroscopy confirmed the surface depletion of PC groups in dry conditions, as nitrogen and phosphorous atoms were found in the bulk of the material but not at the outermost surface layer. The surface enrichment leads to a strongly hydrophilic surface that prevents the adsorption of proteins and reduces the adhesion of cells. The non-functional and hydrophobic reference poly(trimethylene carbonate) (PTMC) adsorbs both proteins and cells, thus the wetting and low adhesion behavior of the PC ionomer can be attributed to the introduced PC functionality. Since the in vivo acceptance of biomaterials is determined by their ability to withstand protein adsorption the PC ionomer described in this paper is highly interesting for a number of in vivo applications in which the adsorption of proteins may be critical, for example, blood contact events.

Adsorption↗

PubMed2006

Effects of hydrolysis on a new biodegradable co-polymer.

The aim of this study was to examine the feasibility of using a new low-modulus biodegradable thermoplastic elastomer for in vivo application as a stent cover. The new polymer, a thermoplastic elastomer, consists of a three-armed co-polymer of poly(lactide)acid (PLLA), poly(trimethylene carbonate) (PTMC) and poly(caprolactone) (PCL). A degradation study was performed in a buffer solution at 37 degrees C for 4 and 6 weeks. The effect of degradation on mechanical properties was studied by stress-strain measurements and explained by using modulated DSC, GPC and mass measurements. A tapered block of PLLA and trimethylene carbonate connecting the crystalline outer part and the inner elastic part was highly susceptible to hydrolysis and caused rapid degradation and subsequent loss of mechanical properties. Random chain scission and homogenous hydrolysis resulted in a loss in mass and molecular weight. After 6 weeks of in vitro hydrolysis the molecular weight had decreased 54% and the elongation-at-break dropped from more than 300% to 90%. A medium free cell seeding study showed that endothelial cells adhered well to the polymeric material. An indicative animal study with the polymer acting as a stent cover showed very low levels of inflammation; however, pronounced neointima thickening was observed which was probably due to the premature failure of the material.

Animals↗

PubMed2006

Intrinsically radiopaque iodine-containing polyvinyl alcohol as a liquid embolic agent: evaluation in experimental wide-necked aneurysms.

OBJECT: To evaluate iodine-containing polyvinyl alcohol (I-PVA) as a precipitating liquid embolic agent, implant characteristics--including radiopacity, setting behavior, and biocompatibility--were studied in an aneurysm model in swine. METHODS: Twelve broad-based carotid artery (CA) sidewall aneurysms were surgically constructed in six pigs. Iodine-containing polyvinyl alcohol dissolved in dimethyl sulfoxide (DMSO) was injected during temporary balloon occlusion bridging the aneurysm neck. Control angiography as well as multidetector row computerized tomography (CT) angiography was performed after 4 weeks. Harvested aneurysms were investigated histopathologically and by 3-tesla high-field magnetic resonance (MR) imaging. The mean degree of aneurysm occlusion achieved was 96%. In two aneurysms a minimal protrusion of I-PVA into the CA lumen was observed. During one embolization, leakage of the liquid embolic agent due to DMSO-induced damage of the microcatheter resulted in CA occlusion. Aneurysms embolized with I-PVA could be discriminated clearly from the parent artery on CT angiograms because there was no beam-hardening artifact. High-field MR imaging allowed a detailed depiction of the liquid embolic distribution within the aneurysm. Histologically, a mild to moderate inflammatory response was found in successfully embolized aneurysms, and the polymer mass was frequently covered by a membrane of fibroblasts and endothelial cells. CONCLUSIONS: Iodine-containing polyvinyl alcohol is a ready-to-use liquid embolic agent clearly visible under fluoroscopy; additives are not required. The setting behavior allows for controlled delivery in aneurysm cavities. Histological studies performed 4 weeks after embolization revealed no sign of toxic tissue response to the liquid embolic agent. Overall, I-PVA exhibits interesting implant characteristics in that radiopaque admixtures are not necessary, thus allowing for artifact-free evaluation of treated aneurysms by using CT and MR angiography.

Aneurysm↗

PubMed2004

Synthesis of tethered-polymer brush by atom transfer radical polymerization from a plasma-polymerized-film-coated quartz crystal microbalance and its application for immunosensors.

This study synthesizes a tethered surface-grafted poly(acrylic acid) with quartz crystal microbalance (QCM) surfaces and provides detailed analysis of their properties and application. A tethered polyelectrolyte brush of poly(acrylic acid) is generated by first covering the substrate with a plasma-polymerized allyl alcohol (pp-AA) film, changing the polymerization initiators (bromination), and then grafting through atom transfer radical polymerization (ATRP) of tert-butyl acrylate (t-BA); these initiators are immobilized on a surface and exposed to a monomer. Finally, we convert the poly(t-BA) brush into poly(acrylic acid) through hydrolysis. We use the QCM technique to measure configuration change of the tethered poly(acrylic acid) grafted chains with two different degrees of polymerization (DP=50,200) in aqueous solutions at three different pH values (4.0, 4.8, and 5.4). The tethered poly(acrylic acid) grafted QCM shows that repeatable frequency responses are induced by pH change of solution. These frequency responses of large DP for pH are 20 times larger than responses of lower DP for pH. The frequency response of antibody immobilization on tethered poly(acrylic acid) grafted QCM (DP=200) and its frequency response of immunoreaction are 10 times larger than conventional immobilization methods by cysteamine with glutalaldehyde coupling of the antibody. The tethered poly(acrylic acid) grafted QCM can increase the frequency response for pH, the immobilization amount of antibody, and immunosensor response.

Acrylic Resins↗

PubMed2004

Phosphoryl choline introduces dual activity in biomimetic ionomers.

Dual activity of phosphoryl choline (PC) functional poly(trimethylene carbonate) (PTMC) was found which induces the zwitterionic biomimetic PC group to form physical cross-links with ionomers in the bulk, and at the same time enrich at the surface of cast films. The formation of zwitterionic domains from a bifunctional PC-PTMC-PC (ionomer) provided firm films with a low elastic modulus in contrast to the tacky PTMC starting material (Mn approximately 3900 g/mol) with poor mechanical performance. In addition, the ionomer possessed improved hemocompatible properties that was explained by the enrichment of PC at the surface, suggesting a way to tailor the mechanical performance of biodegradable PTMC-based ionomers while providing its bioactivity. Tailored elasticity while maintaining hemocompatibility of a biodegradable ionomer should be of particular interest for a variety of in vivo applications.

Biocompatible Materials↗

PubMed2002

Human urothelial cells grown on collagen adsorbed to surface-modified polymers.

OBJECTIVES: Tissue engineering methods can be applied to regenerate diseased, or congenitally missing, urinary tract tissues. Urinary tract tissue cell cultures must be established in vitro and adequate matrices, acting as cell carriers, must be developed. Although degradable and nondegradable polymer matrices offer adequate mechanical stability, they are not optimal for cell adherence and growth. To overcome this problem, extracellular matrix proteins, permitting cell adhesion and regulation of cell proliferation and differentiation, can be adsorbed to the surface-modified polymer. METHODS: In this study, nondegradable polymer films, poly(ethylene terephthalate), were used as an experimental model. Films were modified by graft polymerization of acrylic acid to subsequently allow collagen type I and III immobilization. The following adhesion, proliferation of human urothelial cells, and induction of their stratification were analyzed. RESULTS: Collagen adsorption on 0.2 microg/cm2 poly(acrylic acid)-grafted polymer films rendered the matrix apt for human urothelial cell adhesion and proliferation. Furthermore, stratification of urothelial cells was demonstrated on these surface-modified matrices. CONCLUSIONS: These results have shown that surface-modified polymer matrices can be used to act as cell carriers for cultured human urothelial cells. Such a cell-matrix construct could be applied in reparative surgery of the urinary tract.

Animals↗

PubMed2002

Plasma-induced graft polymerization of acrylic acid onto poly(ethylene terephthalate) films: characterization and human smooth muscle cell growth on grafted films.

Graft polymerization of acrylic acid onto plasma treated poly(ethylene terephthalate) (PET) films was carried out to develop surfaces for protein immobilization and smooth muscle cell seeding. Films with various graft densities were characterized by contact angle measurements, attenuated total reflectance infrared spectroscopy, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The contact angle was observed to decrease from 72.9 degrees for the virgin PET films to between 26 degrees and 33 degrees depending on the graft density. Storage of grafted films led to an increase in the contact angle, suggesting molecular rearrangement at the surface. However, films with the lowest graft levels showed maximum enhancement in the contact angle up on storage. XPS confirmed the presence of the polyacrylic acid grafts at the film surface and AFM showed a marked increase in the wavelength of the surface roughness as the graft density increased. The amount of collagen immobilized at the surface of the grafted films also increased as the graft density increased. The collagen immobilized films provided an excellent substrate for the growth of human smooth muscle cells.

Acrylates↗

PubMed2002

Acrylic acid grafting and collagen immobilization on poly(ethylene terephthalate) surfaces for adherence and growth of human bladder smooth muscle cells.

In tissue engineering, degradable or non-degradable polymer matrices can act as cell-carrier-scaffolds. Cell adhesion and growth on these scaffolds can be promoted by immobilizing extracellular matrix proteins. Therefore, in this study, polymer poly(ethylene terephthalate) (PET) films were surface modified by graft polymerization of acrylic acid, to subsequently allow collagen (types I and III) immobilization and human smooth muscle cell expansion. The surfaces of PET were activated by plasma, followed by acrylic acid graft polymerization, resulting in covalently bound brushes, containing an average of either 0.22+/-0.1 or 5.93+/-0.87 microg/cm2 of poly(acrylic acid) (PAA). Subsequent electrostatic adsorption of collagen gave a surface concentration of 4.96 and 17.2 microg/cm2, respectively, as determined using radiolabelled 125I collagen. Both PET films grafted with 0.22 microg/cm2 of PAA with or without adsorbed collagen were apt for smooth muscle cell adhesion and proliferation. However, films grafted with 5.93 microg/cm2 were not. PAA-grafted PET films, onto which serum proteins of the culture medium adsorbed spontaneously, proved to be better matrices than films on which collagen has been immobilized. It, therefore, can be speculated that other serum proteins are more important than collagen for the human smooth muscle cell adhesion and growth on surface-modified polymer matrices.

Acrylic Resins↗

PubMedDate not supplied

Build-up of collagen and hyaluronic acid polyelectrolyte multilayers.

We have used a novel polyelectrolyte multilayer (PEM) coating consisting of the polyelectrolytes collagen and hyaluronic acid. The build-up by the layer-by-layer deposition technique is outlined by ex situ and in situ ellipsometric measurements. When collagen was added, the thickness of the PEM was increased, and the refractive index was decreased. Corresponding but opposite effects were noted when hyaluronic acid was added. These changes are considered to be explained by a diffusion mechanism. It was also found that the PEM layers were unstable at physiological pH. However, by cross-linking using N-(3-di-methylaminopropyl)-N'-ethylcarbodiimide together with N-hydroxysuccinimide, a stable PEM layer resulted. These tissue friendly PEM layers are expected to have a great impact in the design of artificial extracellular matrixes. Also, the insertion of fluorescence labels demonstrates the potential for incorporation of other functionalities.

Collagen↗

PubMedDate not supplied

Organo hydrogel hybrids. Formation of reservoirs for protein delivery.

A biodegradable organo hydrogel hybrid material is presented, which is formed through the water uptake of a phosphoryl choline zwitterionomer (PC ionomer). The water uptake and subsequent swelling is induced by the phosphoryl choline (PC) end group functionality. The nonfunctional poly(trimethylene carbonate) is hydrophobic and as such does not absorb any water. Disks of the PC ionomer showed significant water uptake, typically above 90 wt % when fully swollen. This high water uptake triggered us to utilize the material for drug and protein loading and subsequent release. Fluorescein and fluorescein-labeled proteins were used as simple models for the loading and release characteristics of the material which was studied by fluorescence spectroscopy. The rate of release of the loaded molecules was compared, and it was shown that the release rate was similar for FITC and insulin but slightly slower for albumin. These results suggest that the PC ionomer may be used as a biodegradable and low elastic modulus material with an additional drug and/or protein release capacity. Such materials are of particular interest for use in a variety of applications in vivo, for example as drug eluting stents.

Albumins↗