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Biomedical subjects

K de Groot

Publications and source records attributed to K de Groot.

At least 37 records · Page 2Linked to original sources
PubMed2004

Osteoinductive implants: the mise-en-scène for drug-bearing biomimetic coatings.

In orthopaedic and dental implantology, novel tools and techniques are being sought to improve the regeneration of bone tissue. Numerous attempts have been made to enhance the osteoconductivity of titanium prostheses, including modifications in their surface properties and coating with layers of calcium phosphate. The technique whereby such layers are produced has recently undergone a revolutionary change, which has had profound consequences for their potential to serve as drug-carrier systems. Hitherto, calcium phosphate layers were deposited upon the surfaces of metal implants under highly unphysiological physical conditions, which precluded the incorporation of proteinaceous osteoinductive drugs. These agents could only be adsorbed, superficially, upon preformed layers. Such superficially adsorbed molecules are released too rapidly within a biological milieu to be effective in their osteoinductive capacity. Now, it is possible to deposit calcium phosphate layers under physiological conditions of temperature and pH by the so-called biomimetic process, during which bioactive agents can be coprecipitated. Since these molecules are integrated into the inorganic latticework, they are released gradually in vivo as the layer undergoes degradation. This feature enhances the capacity of these coatings to act as a carrier system for osteogenic agents.

Animals↗
PubMed2004

In vitro/in vivo correlation for 14C-methylated lysozyme release from poly(ether-ester) microspheres.

PURPOSE: The purpose of this study was to obtain an in vitro/in vivo correlation for the sustained release of a protein from poly(ethylene glycol) terephthalate (PEGT)/poly(butylene terephthalate) (PBT) microspheres. METHODS: Radiolabeled lysozyme was encapsulated in PEGT/PBT microspheres via a water-in-oil-in-water emulsion. Three microsphere formulations varying in copolymer composition were administered subcutaneously to rats. The blood plasma was analyzed for radioactivity content representing released lysozyme at various time points post-dose. The in vitro release was studied in phosphate-buffered saline. RESULTS: The encapsulation efficiency, calculated from the radioactivity in the outer water phase of the emulsion, varied from 60-87%. Depending on the PEG segment length and wt% PEGT, the lysozyme was released completely in vitro within 14 to 28 days without initial burst. 14C-methylated lysozyme could be detected in the plasma over the same time courses. The in vitro/in vivo correlation coefficients obtained from point-to-point analysis were greater than 0.96 for all microsphere formulations. In addition, less then 10% of administered radioactivity remained at dose site at 28 days for the microsphere formulations, indicating no notable retention of the protein at the injection site. CONCLUSION: The in vitro release in phosphate-buffered saline and the in vivo release in rats showed an excellent congruence independent of the release rate of 14C-methylated lysozyme from PEGT/PBT microspheres.

Animals↗
PubMed2004

Preparation and characterization of electrodeposited calcium phosphate/chitosan coating on Ti6Al4V plates.

Electrolytically deposited carbonate apatite coating demonstrates higher strength but weaker support for bone marrow stromal cell attachment than do biomimetically deposited coatings. It is hypothesized that the incorporation of chitosan will increase the biocompatibility of electrolytic coating while maintaining its original strength. To verify this hypothesis, we formed a hybrid calcium phosphate/chitosan coating through electrodeposition. We found that the incorporation of chitosan influenced calcium phosphate formation and crystallization. Moreover, coating thickness and surface roughness decreased with increasing chitosan concentration. Hybrid coating exhibited an increased dissolution rate in both acidic and neutral simulated physiologic solution, whereas no significant difference on adhesive strength was found between the hybrid and original coatings (P > 0.05). Most importantly, the calcium phosphate/chitosan coating proved to be a more favorable surface for goat bone marrow stromal cell attachment than an unincorporated coating (P < 0.01). Considering its economic and simple production, a hybrid calcium phosphate/chitosan coating is thought to be an attractive candidate for future applications.

Alloys↗
PubMed2004

Churg Strauss syndrome--successful induction of remission with methotrexate and unexpected high cardiac and pulmonary relapse ratio during maintenance treatment.

OBJECTIVE: To examine the safety and efficacy of methotrexate (MTX) plus low-dose prednisolone for induction of remission in non life- or organ-threatening courses and for remission maintenance in Churg-Strauss syndrome (CSS). METHODS: In an open-label study 11 patients were treated with MTXfor induction of remission at initial diagnosis and relapse. Twenty-five patients received MTX for maintenance of remission. Primary endpoints were the achievement of remission and the incidence of relapses, respectively. Doses of concomitant prednisolone (PRD) and side effects were secondary endpoints. RESULTS: Induction of remission was achieved in 8/11 patients with MTX/PRD. Median time to remission was 5 months (range 2-9). Remission was maintained in 12 of 23 with available long-term follow-up (median 48 months). Eleven patients experienced 8 major and 3 minor relapses with a median time from remission to first relapse of 9 months. With MTX, the median cumulative PRD dose during the induction phase was 6.2 g. In the maintenance phase PRD could be reduced by 53% in responders. Apart from one case of MTX-induced pneumonitis, adverse events were confined to mild/moderate episodes of infection and leucopenia. No opportunistic infections occurred, neither did steroid-specific adverse events. CONCLUSIONS: MTX is safe and effective for the induction of remission in non-life-threatening CSS. It allows a considerable reduction of PRD and thus avoidance of PRD-related adverse events. However, the ability of MTX to prevent relapses in CSS appears limited. The identification of an optimal maintenance regimen and prognostic factors for treatment response requires trials with larger patient numbers.

Adolescent↗
PubMed2003

Remineralization of demineralized albumin-calcium phosphate coatings.

Calcium phosphate and bovine serum albumin were coprecipitated (under physiological conditions of temperature and pH) upon the surfaces of titanium-alloy samples, which thereby became coated with a dense, proteinaceous mineral layer 30-50 microm in thickness. Dissolution of the inorganic phase by treatment with acidic saline yielded a self-supporting protein scaffold, 7-10 microm in thickness. Energy-dispersive X-ray analysis and Fourier-transform infrared spectroscopy confirmed the absence of inorganic components from the demineralized albumin scaffolds. When titanium-alloy samples bearing these demineralized protein scaffolds were immersed in a supersaturated solution of calcium phosphate (again at physiological temperature and pH), they remineralized. These redux albumin-calcium phosphate layers corresponded in thickness to the original coatings. When titanium-alloy discs bearing the demineralized protein scaffolds were implanted ectopically (subcutaneously) in mice, they, too, remineralized. No uniform mineral layer was deposited upon the surfaces of naked titanium-alloy implants. To the best of our knowledge, this is the first demonstration of remineralization within the interstices of a noncollagenous protein scaffold, either in vitro or in vivo.

Alloys↗
PubMed2003

Biodegradable poly(ether-ester) multiblock copolymers for controlled release applications.

Multiblock poly(ether-ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate units were synthesized by a two-step melt polycondensation reaction, with the aim of developing a new series of degradable polymers for controlled release applications. The copolymers were characterized with respect to their composition (NMR), thermal properties (DSC), and swelling. The main focus was on the degradation kinetics and release properties of the copolymers. The crystallinity and swelling could be tailored by the PEG segment length and the ratio of the building units. With increasing mol fraction succinate in the hard segment, the swelling increased. The in vitro degradation was found to occur by molecular weight decrease and mass loss. Substitution of the aromatic terephthalate units by aliphatic succinate units increased the degradation rate of the copolymers. Polymers with PEG segments of 1000 kg/mol showed a more pronounced degradation than copolymers containing shorter and longer PEG segments. Model proteins were successfully incorporated and released from the poly(ether-ester) films. Depending on the size of the protein, the release mechanism was based on diffusion of the protein and degradation of the matrix.

Animals↗
PubMed2003

Osteointegration of biomimetic apatite coating applied onto dense and porous metal implants in femurs of goats.

Biomimetic calcium phosphate (Ca-P) coatings were applied onto dense titanium alloy (Ti6Al4V) and porous tantalum (Ta) cylinders by immersion into simulated body fluid at 37 degrees C and then at 50 degrees C for 24 h. As a result, a homogeneous bone-like carbonated apatitic (BCA) coating, 30 microm thick was deposited on the entire surface of the dense and porous implants. Noncoated and BCA-coated implants were press-fit implanted in the femoral diaphysis of 14 adult female goats. Bone contact was measured after implantation for 6, 12, and 24 weeks, and investigated by histology and backscattered electron microscopy (BSEM). After 6 weeks, bone contact of the BCA-coated Ti6Al4V implants was about 50%. After 12 and 24 weeks, bone contact was lower in comparison with the 6-week implantations at, respectively 24 and 39%. Regarding the BCA-coated porous Ta implants, bone contacts were 17, 30, and 18% after 6, 12, and 24 weeks, respectively. However, bone contact was always found significantly higher for BCA-coated dense Ti6Al4V and porous Ta cylinders than the corresponding noncoated implants. The results of this study show that the BCA coating enhances the bone integration as compared to the noncoated implants.

Alloys↗
PubMed2003

A novel method to obtain protein release from porous polymer scaffolds: emulsion coating.

To obtain the controlled release of proteins from macro-porous polymeric scaffolds, a novel emulsion-coating method has been developed. In this process, a water-in-oil emulsion, from an aqueous protein solution and a polymer solution, is forced through a prefabricated scaffold by applying a vacuum. After solvent evaporation, a polymer film, containing the protein, is then deposited on the porous scaffold surface. This paper reports the effect of processing parameters on the emulsion coating characteristics, scaffold structure, and protein release and stability. Poly(ether-ester) multiblock copolymers were chosen as the polymer matrix for both scaffolds and coating. Macro-porous scaffolds, with a porosity of 77 vol% and pores of approximately 500 microm were prepared by compression moulding/salt leaching. A micro-porous, homogeneous protein-loaded coating could be obtained on the scaffold surface. Due to the coating, the scaffold porosity was decreased, whereas the pore interconnection was increased. A model protein (lysozyme) could effectively be released in a controlled fashion from the scaffolds. Complete lysozyme release could be achieved within 3 days up to more than 2 months by adjusting the coated emulsion parameters. In addition, the coating process did not reduce the enzymatic activity. This new method appears to be promising for tissue engineering applications.

Animals↗
PubMed2003

In vitro and in vivo degradation of biomimetic octacalcium phosphate and carbonate apatite coatings on titanium implants.

Calcium phosphate (Ca-P) coatings have been applied onto titanium alloys prosthesis to combine the srength of metals with the bioactivity of Ca-P. It has been clearly shown in many publications that Ca-P coating accelerates bone formation around the implant. However, longevity of the Ca-P coating for an optimal bone apposition onto the prosthesis remains controversial. Biomimetic bone-like carbonate apatite (BCA) and Octacalcium Phosphate (OCP) coatings were deposited on Ti6Al4V samples to evaluate their in vitro and in vivo dissolution properties. The coated plates were soaked in alpha-MEM for 1, 2, and 4 weeks, and they were analyzed by Back Scattering Electron Microscopy (BSEM) and by Fourier Transform Infra Red spectroscopy (FTIR). Identical coated plates were implanted subcutaneously in Wistar rats for similar periods. BSEM, FTIR, and histomorphometry were performed on the explants. In vitro and in vivo, a carbonate apatite (CA) formed onto OCP and BCA coatings via a dissolution-precipitation process. In vitro, both coatings dissolved overtime, whereas in vivo BCA calcified and OCP partially dissolved after 1 week. Thereafter, OCP remained stable. This different in vivo behavior can be attributed to (1) different organic compounds that might prevent or enhance Ca-P dissolution, (2) a greater reactivity of OCP due to its large open structure, or (3) different thermodynamic stability between OCP and BCA phases. These structural and compositional differences promote either the progressive loss or calcification of the Ca-P coating and might lead to different osseointegration of coated implants.

Alloys↗
PubMed2003

[Therapy of primary systemic vasculitis].

The treatment of systemic vasculitides has changed during the past ten years from a uniform immunosuppressive regimen consisting of cyclophosphamide and prednisolone to a stage- and activity-adapted, more differentiated immunosuppressive and immunomodulating therapy. Due to the low incidence of these diseases, the assessment of these regimens by prospective, randomized, controlled trials has only been enabled through multicenter cooperation. In primary systemic vasculitides of small- or medium-sized vessels induction of remission therapy comprises methotrexate in early generalized disease without significant renal insufficiency, cyclophosphamide in full-blown generalized disease and additional plasma exchanges in cases of rapidly progressive glomerulonephritis if oliguric, each in conjunction with oral prednisolone. After achievement of remission patients are switched to a less potent maintenance of remission therapy with better long-term tolerability, such as azathioprine. Glucocorticoids are the mainstay for large vessel vasculitides, supplemented by azathioprine or methotrexate in cases of critical organ perfusion or demand for high steroid doses. Therapy for secondary vasculitides relies essentially on the treatment of the underlying disease, which means virus elimination in cases of hepatitis B or C associated vasculitides. Immunosuppression in these diseases is reserved for organ- or life-threatening manifestations only.

Adjuvants, Immunologic↗
PubMed2003

Proteins incorporated into biomimetically prepared calcium phosphate coatings modulate their mechanical strength and dissolution rate.

In a previous investigation, we demonstrated that when bovine serum albumin (BSA) is biomimetically co-precipitated with Ca(2+) and PO(4)(3-) ions upon titanium-alloy implants, it becomes incorporated into the crystal lattice and is not merely deposited on its surface. Moreover, the protein elicited a change in crystal structure from an octacalcium phosphate type to a carbonated apatite one, which bears a closer resemblance to natural bone mineral. In the present study, we investigated the dissolution rate and mechanical strength of such BSA-containing coatings as a function of protein concentration within the bathing medium (10 ng/ml to 1.0 mg/ml). BSA-containing coatings released Ca(2+) ions more slowly (5 ppm/min) than did non-BSA-containing ones (10 ppm/min), but this rate did not change as a function of protein concentration within the bathing medium. In contrast, the strength of coatings increased almost linearly as a function of protein concentration within the bathing medium, indicating that BSA incorporated into the crystal lattice enhances its mechanical strength in a concentration-dependent manner.

Alloys↗
PubMed2003

Release of small water-soluble drugs from multiblock copolymer microspheres: a feasibility study.

Poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) multiblock copolymer was investigated as a possible matrix for controlled delivery of small water-soluble drugs. Two molecules were selected as sustained release candidates from microspheres: leuprorelin acetate (peptide of Mw = 1270 D) and vitamin B(12) (Mw = 1355 D). First, vitamin B(12)-loaded microspheres were prepared using a double emulsion method and preparation parameters were varied (surfactant in the first emulsion and copolymer composition). The resulting microsphere structure, entrapment efficiency and release rate were evaluated. Vitamin B(12)-loaded microsphere parameters could easily be tailored to achieve specific requirements. The addition of surfactant in the first preparation process led to a significant increase of the microsphere entrapment efficiency, whereas the decrease of the PEGT copolymer content allowed the release rates from microspheres to be precisely decreased. However, leuprorelin acetate-loaded microspheres did not show the same characteristics when prepared with the same parameters, possibly because of a high water solubility discrepancy between the vitamin B(12) and the peptide. This study shows the suitability of PEGT/PBT microspheres as a controlled release system for vitamin B(12), but not for leuprorelin acetate. It also underlines the necessity of tailored development for each individual drug and emphasizes the risk of using model molecules.

Delayed-Action Preparations↗
PubMed2003

Evaluation of two biodegradable polymeric systems as substrates for bone tissue engineering.

The aim of this study was to evaluate two biodegradable polymeric systems as scaffolds for bone tissue engineering. Rat bone marrow cells were seeded and cultured for 1 week on two biodegradable porous polymeric systems, one composed of poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) and the other composed of cornstarch blended with poly(epsilon-caprolactone) (SPCL). Porous hydroxyapatite granules were used as controls. The ability of cells to proliferate and form extracellular matrix on these scaffolds was assessed by a DNA quantification assay and by scanning electron microscopy examination; their osteogenic differentiation was screened by the expression of alkaline phosphatase. In addition, the in vivo osteogenic potential of the engineered constructs was evaluated through ectopic implantation in a nude mouse model. Results revealed that cells were able to proliferate, differentiate, and form extracellular matrix on all materials tested. Moreover, all constructs induced abundant formation of bone and bone marrow after 4 weeks of implantation. The extent of osteogenesis (approximately 30% of void volume) was similar in all types of implants. However, the amount of bone marrow and the degree of bone contact were higher on HA scaffolds, indicating that the polymers still need to be modulated for higher osteoconductive capacity. Nevertheless, the findings suggest that both PEGT/PBT and SPCL systems are excellent candidates to be used as scaffolds for a cell therapy approach in the treatment of bone defects.

Alkaline Phosphatase↗
PubMed2002

Stability aspects of salmon calcitonin entrapped in poly(ether-ester) sustained release systems.

Poly(ether-ester)s composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were studied as matrix for the controlled release of calcitonin. Salmon calcitonin loaded PEGT/PBT films were prepared from water-in-oil emulsions. The initial calcitonin release rate could be tailored by the copolymer composition, but incomplete release of calcitonin was observed. FTIR measurements indicated aggregation of calcitonin in the matrix, which was not due to the preparation method of the matrices, but due to the instability of calcitonin in an aqueous environment. Release experiments showed the susceptibility of calcitonin towards the composition of the release medium, in particular to the presence of metal ions. With increasing amount of sodium ions, a decrease in the total amount of released calcitonin was observed due to enhanced aggregation. The calcitonin had to be stabilized in the matrix to prevent aggregation. Incorporation of sodium dodecyl sulphate (SDS) as a stabilizer in PEGT/PBT matrices increased the percentage of calcitonin released, but could not avoid aggregation on a longer term.

Animals↗
PubMed2002

Biomimetic calcium phosphate coatings on Polyactive 1000/70/30.

Precalcification of Polyactive 1000/70/30 with a biomimetic calcium phosphate coating is expected to enhance the bioactivity of this biodegradable polymer for the application as bone filler or scaffold of bone tissue engineering. This study presents a 1-day one-step incubation method to obtain either amorphous or bone-like apatitic calcium phosphate coating on Polyactive 1000/70/30. Either dense plates or three-dimensional porous blocks of the polymer were incubated in a simplified but concentrated simulated body fluid-derived solution at 37 degrees C. By bubbling CO2 gas, a solution was prepared with calcium and phosphate ion concentrations five times of that of regular simulated body fluid. With controlled stirring, the CO2 was released out of the solution and exchanged by air. The pH of the solution increased to induce coating formation. Adjusting stirring rate and CO2/air exchange rate controlled the process kinetics. The reaction kinetics had little influence on the crystallographic structure of the final coating mineral for a given solution composition as shown by Fourier transform infrared spectroscopy and X-ray diffraction. However, the interface structure between the coating and substrate was kinetics-dependent. A fast precipitation condition resulted in a uniform but superficial calcification pattern at the surface of polymer. A slow process by selecting either a slow stirring or a slow CO2/air exchange, on the contrary, induced a localized but deep inside calcification pattern. A tensile test showed no statistically significant difference in the mechanical properties among uncoated and coated polymers. The cracking behavior of coatings from different kinetics, however, exhibited different manners, as can be attributed to different interface structures and interfacial strengths.

Bone Substitutes↗
PubMed2002

Control of vitamin B12 release from poly(ethylene glycol)/poly(butylene terephthalate) multiblock copolymers.

The release of vitamin B12 (1355 Da) from matrices based on multiblock copolymers was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion method. The copolymer properties, like permeability, could be varied by increasing the PEG-segment length from 300 up to 4,000 g/mol and by changing the wt% of PEGT. From permeation and release experiments. the diffusion coefficient of vitamin B12 through PEGT/PBT films of different compositions was determined. The diffusion coefficient of Vitamin B12 was strongly dependent on the composition of the copolymers. Although an increased wt% of PEGT (at a constant PEG-segment length) resulted in a higher diffusion coefficient, a major effect was observed at increasing PEG-segment length. By varying the copolymer composition, a complete release of vitamin B12 in 1 day up to a constant release for over 12 weeks was obtained. The release rate could be effectively tailored by blending copolymers with different PEG-segment lengths. The swelling and the crystallinity of the matrix could explain the effect of the matrix composition on the release behavior.

Biocompatible Materials↗
PubMed2002

Influence of ionic strength and carbonate on the Ca-P coating formation from SBFx5 solution.

Biomimetic calcium-phosphate (Ca-P) coatings were applied on Ti6Al4V by using simulated body fluids concentrated by a factor 5 (SBFx5). The production of SBFx5 solution was possible by decreasing the pH of the solution to approximately 6 using CO2 gas. The subsequent release of this mildly acidic gas led to a pH rise and thus, increasing supersaturation. After immersion for 5(1/2) h a Ca-P coating on Ti6Al4V plates and a precipitate simultaneously formed at pH = 6.8. Sodium chloride (NaCl) and hydrogencarbonate (HCO3) contents were studied in relation to CO2 release and coating formation by changing their individual concentration in SBFx5 solution. On one hand, NaCl-free or low NaCl-content SBFx5 solution led to the earlier aspecific precipitation in the solution than for SBFx5 solution. In contrast, Ca-P coating was formed later and was thinner than the coating obtained in regular SBFx5 solution. High ionic strength delayed precipitation and favored Ca-P heterogeneous nucleation on Ti6Al4V. On the other hand, HCO3- content increased the pH of the solution due to its buffering capacity and influenced the release rate of dissolved CO2. Thus, HCO3- content strongly affected the supersaturation and Ca-P structure. Furthermore, HCO3- favored the attachment of Ca-P mineral on Ti6Al4V by decreasing Ca-P crystal size resulting in a better physical attachment of Ca-P coating on Ti6Al4V substrate.

Alloys↗