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Biomedical subjects

K De Groot

Publications and source records attributed to K De Groot.

At least 19 recordsLinked to original sources

Influence of octacalcium phosphate coating on osteoinductive properties of biomaterials.

In this study, we investigated the influence of octacalcium phosphate (OCP) coating on osteoinductive behaviour of the biomaterials. Porous titanium alloy (Ti6Al4V), hydroxyapatite (HA), biphasic calcium phosphate (BCP) and polyethylene glyco terephtalate/polybuthylene terephtalate (PEGT-PBT) copolymer, all uncoated and coated with biomimetically produced OCP, were implanted in back muscles of 10 goats for 6 and 12 weeks. Uncoated Ti6Al4Vand HA did not show any bone formation after intramuscular implantation. All OCP coated implants, except PEGT-PBT, did induce bone in the soft tissue. The reason for the non-inductive behaviour of the copolymer is probably its softness, that makes it impossible to maintain its porous shape after implantation. Both uncoated and OCP coated BCP induced bone. However, the amount of animals in which the bone was induced was higher in the coated BCP implants in comparison to the uncoated ones. Osteoinductive potential of biomaterials is influenced by various material characteristics, such as chemical composition, crystallinity, macro- and microstructure. OCP coating has a positive effect on osteoinductivity of the biomaterials. The combination of the advantages of biomimetic coating method above traditional methods, and a good osteoinductivity of OCP coating that is produced by using this method, opens new possibilities for designing more advanced orthopaedic implants.

Alloys↗

Factors having influence on the rheological properties of Ti6A14V slurry.

A highly porous Ti6Al4V could be produced with a porous polymeric sponge and Ti6Al4V slurry. However, the rheological properties of Ti6Al4V slurry appeared to be the key issue in the preparation of porous Ti6Al4V. In this study, factors having influence on the rheological properties of Ti6Al4V slurry were addressed in detail. Ti6Al4V powders, organic thickening agents (binders), dispersants, concentration of powder and pH values were optimised with regard to the rheological properties of Ti6Al4V slurry. The results show that Ti6Al4V powder with a mean diameter of 45 microm and spherical shape is beneficial for the preparation of Ti6Al4V slurry. Meanwhile binders with two ingredients, which decompose at different temperatures, have the advantage to keep the shape after debinding. The optimised procedure, based on the findings, made it possible to produce highly porous Ti6Al4V with reticulate porous structure. Porous Ti6Al4V produced by this way is expected to be a promising biomaterial for tissue engineering scaffolds and orthopaedic implant applications.

Alloys↗

[Pulmonary renal syndrome].

Pulmonary-renal syndrome is a potentially life-threatening disorder, characterised by diffuse alveolar hemorrhage on the basis of pulmonary capillaritis in association with rapidly progressive glomerulonephritis. It can originate from various systemic autoimmune diseases. ANCA-associated vasculitides account for approximately 60% and Goodpasture's syndrome for approximately 20% of the cases. Fulminant pulmonary capillaritis can result in acute respiratory failure with the more subtle forms only being detectable by bronchoalveolar lavage. Kidney biopsy displays extracapillary proliferating glomerulonephritis and renal immunohistology facilitates detection of the underlying systemic disease. By accelerating the diagnosis of the specific underlying disease, auto-antibody testing fosters rapid initiation of treatment and thereby strongly improves the prognosis of pulmonary-renal syndrome. Intense immunosuppression with cyclophosphamide and glucocorticoids, augmented by plasmapheresis in the event of Goodpastures's syndrome, is the mainstay of therapy. Supportive measures such as temporary ventilation and hemodialysis have further reduced mortality.

Anti-Glomerular Basement Membrane Disease↗

A comparison of the osteoinductive potential of two calcium phosphate ceramics implanted intramuscularly in goats.

The osteoinductive potential, or bone induction potency, of two calcium phosphate ceramics was evaluated after intramuscular implantation in goats. The ceramics were comprised of hydroxyapatite (HA) and biphasic calcium phosphate (BCP), the later of which contained a 85/15 mixture of hydroxyapatite and tricalcium phosphate (TCP). Both ceramics had a similar macroporosity of around 55% and a pore distribution between 100 and 800 microm. Besides the difference in chemistry, BCP was also microporous and hence had a different surface microstructure. After implantation in the back muscles of four goats for 12 weeks, all 8 BCP samples (7x7x7 mm(3)) showed the presence of bone formation in the macropores (1+/-1%), while no bone was found in any of the HA samples. The used BCP can therefore be characterized as an osteoinductive material. Having the ability to induce bone formation in soft tissues, the BCP presented herein may be a useful biomaterial for bone repair when combined with cultured osteogenic cells, growth factors or both.

Journal Article↗

Material-dependent bone induction by calcium phosphate ceramics: a 2.5-year study in dog.

Bone induction by different calcium phosphate biomaterials has been reported previously. With regard to (1) whether the induced bone would disappear with time due to the absence of mechanical stresses and (2) whether this heterotopically formed bone would give rise to uncontrolled growth, a long-time investigation of porous hydroxyapatite ceramic (HA), porous biphasic calcium phosphate ceramic (TCP/HA, BCP), porous alpha-tricalcium phosphate ceramic (alpha-TCP) and porous beta-tricalcium phosphate ceramic (beta-TCP) was performed in dorsal muscles of dog, for 2.5 years. Histological observation, backscattered scanning electron microscopy observation and histomorphometric analysis were made on thin un-decalcified sections of retrieved samples. Normal compact bone with bone marrow was found in all HA implants (n = 4) and in all BCP implants (n = 4), 48 +/- 4% pore area was filled with bone in HA implants and 41 +/- 2% in BCP implants. Bone-like tissue, which was a mineralised bone matrix with osteocytes but lacked osteoblasts and bone marrow, was found in all beta-TCP implants (n = 4) and in one of the four alpha-TCP implants. Both normal bone and bone-like tissues were confined inside the pores of the implants. The results show that calcium phosphate ceramics are osteoinductive in muscles of dogs. Although the quality and quantity varied among different ceramics, the induced bone in both HA and BCP ceramics did neither disappear nor grow uncontrollably during the period as long as 2.5 years.

Animals↗

Biomimetic coatings on titanium: a crystal growth study of octacalcium phosphate.

The biomimetic approach allows the coating of metal implants with different calcium-phosphate (Ca-P) phases. Films elaborated at physiological conditions exhibited structures closely resembling those of bone mineral. For instance, octacalcium phosphate (OCP, Ca8(HPO4)2(PO4)4 . 5H2O) crystals have been deposited on titanium through a two-step procedure. After cleaning and etching, Ti6Al4V plates were immersed for 24 h into a simulated body fluid (SBF1). A thin amorphous carbonated Ca-P layer precipitated on the metal substrate. Secondly, these thinly Ca-P coated titanium substrates were immersed for 48 h into another simulated body fluid (SBF2). The thin amorphous carbonated Ca-P layer induced the fast precipitation of a second Ca-P layer of 55 microm in thickness composed of OCP crystals. The measurements of Ca and P concentrations versus soaking time in SBF2 showed that the carbonated Ca-P layer partially dissolved before the deposition of the OCP coating. X-ray diffraction (XRD) revealed that OCP crystals grew epitaxially on the substrate. OCP is known to be one of the precursors during the bone mineralization process, thereby, this new generation of biomimetic coatings are promising for orthopedic surgery.

Journal Article↗

Use of an osteoinductive biomaterial as a bone morphogenetic protein carrier.

A porous calcium phosphate ceramic, which induced bone formation in soft tissues of dogs, was termed as osteoinductive biomaterial and studied as a carrier of bone morphogenetic protein (rhBMP-2). Cylinder implants (laser spot 4 x 5 mm) impregnated with 0, 1, 10 and 40 microg rhBMP-2 were implanted in dorsal muscles of rabbits for five weeks. Histological observation and histomorphometric analysis were performed on thin un-decalcified sections. No bone formation was detected in the implants without rhBMP-2, while mature lamellar bone was found inside the implants with 1 microg rhBMP-2, both on the outer surface and inside the implants with 10 microg and 40 microg rhBMP-2. Little difference in formed bone was found between 1 microg and 10 microg rhBMP-2, but no difference was found between 10 microg and 40 microg rhBMP-2. A significant difference in bone marrow formation was found among 1, 10 and 40 microg rhBMP-2. The more rhBMP-2, the more bone marrow formed. The present results indicate that osteoinductive biomaterial is a good carrier of BMP and high dose of BMP is not necessary for bone formation in clinic.

Journal Article↗

Bone formation induced by calcium phosphate ceramics in soft tissue of dogs: a comparative study between porous alpha-TCP and beta-TCP.

Two kinds of tri-calcium phosphate ceramics (Ca/P = 1.50), alpha-TCP and beta-TCP, which has the same macrostructure and microstructure, but different phase composition, were implanted in dorsal muscles of dogs. The samples were retrieved at 30, 45 and 150 days, respectively, after implantation, and were analyzed histologically. There were critically different tissue responses between alpha-TCP ceramic and beta-TCP ceramic. Higher cell populations were observed inside the pores of beta-TCP than those of alpha-TCP, bone tissue was found in beta-TCP at 45 and 150 days, but no bone formation could be detected in any alpha-TCP implants in this study. On the other hand, the bone tissue in beta-TCP seemed to degenerate at 150 days. The results indicate that porous beta-TCP can induce bone formation in soft tissues of dogs; while the rapid dissolution of the ceramic and the higher local Ca2+, PO(4)3- concentration due to the rapid dissolution of alpha-TCP may resist bone formation in alpha-TCP and the less rapid dissolution of beta-TCP may be detrimental to already formed bone in beta-TCP.

Journal Article↗

Local low-dose IL-2 therapy.

Interleukin-2 (IL-2) is a powerful drug for treating cancer. However, it is only powerful if it is properly applied. That is, IL-2 should be applied at the tumor site, because at the transition of normal and malignant tissue are the tumor infiltrating cells. These should be activated by IL-2. Local application implies that IL-2 can be used in relatively low doses. It is becoming clear that even a single injection of IL-2 can cure cancer. IL-2 can also enhance the therapeutic effects of irradiation and Cisplatin. Locally applied IL-2 therapy is virtually non-toxic.

Animals↗

Preparation of bioactive microporous titanium surface by a new two-step chemical treatment.

Microporous oxide layers allowing fast deposition of calcium phosphate layers (CPLs) were formed on commercially pure titanium (c.p.Ti) after the application of a newly developed two-step chemical treatment. The micropores were of submicrometre size. The two-step treatment was carried out by etching c.p.Ti samples with HCl and H2SO4 first and then treating them in boiling 0.2 N NaOH solution at 140 degrees C for 5 h. Conformal CPLs, about 20 microm thick, were deposited on the two-step treated c.p.Ti surface by means of a two-day immersion in an in vitro supersaturated calcification solution. The CPL was characterized to be mainly composed of two sublayers, i.e. an outside loose octacalcium phosphate crystal sublayer and an inside dense carbonated apatite sublayer. A scratching test indicated that the apatite sublayer was strongly bonded to the c.p.Ti substrate. Moreover, it was observed that the untreated or single-step treated c.p.Ti surfaces are not only morphologically different from one another but significantly different from the two-step treated one, in that no precipitation was observed on them up to 14 d immersion in the same calcification solution. It is indicated that the two-step chemical treatment is a simple and easily controllable method to prepare bioactive titanium surfaces and subsequently to induce the rapid precipitation of conformal and adherent CPL from in vitro supersaturated calcification solutions.

Journal Article↗

In vitro testing of surface-modified biomaterials.

The influence of surface modification treatments such as ion implantation and sputter coating on an in vitro rat bone-marrow cell culture was studied by scanning electron microscopy and X-ray microanalysis. 316 L stainless steel, Ti-6Al-4V and Ti-5Al-2.5Fe were nitrogen ion-implanted with three fluences: 10(15), 10(16) and 10(17) ion cm-2 with an energy beam of 40 keV. Both nitrogen and carbon sputter-coated 316 L stainless steel samples were also studied. Polished 316 L stainless steel, Ti-6Al-4V, Ti-5Al-2.5Fe and Thermanox were also studied, in order to give comparative information. The materials were inoculated with a droplet of cell suspension and were maintained for 3 wk. A mineralized extracellular matrix was formed on all materials except on nitrogen sputter-coated 316 L stainless steel. The morphology of the cell cultures obtained on nitrogen-ion implanted materials was similar to those obtained on the untreated materials and Thermanox. The observation of the interface between the cell layer and the substrata showed the presence of calcium- and phosphorus-rich globular deposits associated with collagen fibres. A higher density of these globular deposits was observed on the ion-implanted materials.

Journal Article↗

Osteoinduction by calcium phosphate biomaterials.

Different materials were implanted in muscles of dogs to study the osteoinduction of calcium phosphate biomaterials. Bone formation was only seen in calcium phosphate biomaterials with micropores, and could be found in hydroxyapatite (HA) ceramic, tricalcium phosphate/hydroxyapatite ceramic (BCP), beta-TCP ceramic and calcium phosphate cement. The osteoinductive potential was different in different materials. The results indicate that osteoinduction can be a property of calcium phosphate biomaterials when they exhibit specific chemical and structural characteristics.

Journal Article↗

Bone morphogenetic protein and ceramic-induced osteogenesis.

To investigate the relationship between bone morphogenetic proteins (BMP) and calcium phosphate ceramic-induced osteogenesis in soft tissues, in vitro and in vivo experiments were performed. In an in vitro study, the ability of different calcium phosphate ceramics to absorb bovine BMP (bBMP) from a bBMP solution was tested. In vivo studies included immunohistochemical BMP staining before bone formation in the ceramics was detected, and the enhancement of bone formation in calcium phosphate ceramics by bBMP. The results were: (1) calcium phosphate ceramics have a strong ability to absorb bBMP; (2) a high BMP concentration reaches inside the ceramic implants before bone formation in soft tissues of domestic pig occurs; (3) by 56% at 50 d and by 23% at 100 d, bBMP enhances bone formation in calcium phosphate ceramics implanted in soft tissues of dogs. The results indicate the BMP plays an important role in calcium phosphate ceramic-induced osteogenesis and that adsorption of native BMP from the body fluids to ceramic implants may be a key step in osteoinduction by calcium phosphate ceramics.

Journal Article↗

A simple method to prepare calcium phosphate coatings on Ti6Al4V.

A two-step chemical treatment followed by immersion in a supersaturated calcification solution (SCS) was found to be a simple way to prepare calcium phosphate (Ca-P) coatings on Ti6Al4V. The Ca-P deposition on the treated metallic surfaces could be accelerated by employing a pre-calcification (Pre-Ca) procedure prior to immersion in SCS. The two-step treatment was performed by etching the metallic plates with a mixture of HCl and H2SO4 followed by ageing in boiling diluted NaOH solution at 140 degrees C. Pre-Ca was carried out by incubating the two-step treated plates in Na2HPO4 solution and then in saturated Ca(OH)2 solution. The formation of a bioactive microporous surface oxide layer on Ti6Al4V by the two-step treatment was most probably responsible for the induction of Ca-P precipitation. The deposition rates and compositions of Ca-P coatings in two different SCSs were investigated by means of scanning electron microscopy, X-ray diffraction and infrared spectrophotometry.

Journal Article↗

Response to trimethoprim/sulfamethoxazole in Wegener's granulomatosis depends on the phase of disease.

We prospectively studied trimethoprim/sulfamethoxazole (T/S) in inducing remission in 'initial phase' Wegener's granulomatosis (WG), and in sustaining remission in generalized WG, in 72 patients in various disease stages. Nineteen patients with initial phase WG received T/S (2 x 960 mg/day). Another 24 patients with generalized WG received the same dose of T/S (group A) and were compared with 21 patients receiving no further treatment after standard therapy (group B). Eight patients were given T/S plus low-dose prednisone (group C). Eleven of 19 patients (58%) with initial phase WG achieved complete or partial remission lasting a median 43 months (range 6-88 months). Of the remaining eight (42%), five showed local disease progression, and three developed generalized WG. In group A (T/S alone, generalized WG), 10/24 (42%) suffered a relapse after a median 13 months (range 4-58 months). In group B (generalized WG, no further treatment) 29% of patients relapsed after a median 22.5 months (range 18-26 months). All eight patients treated with T/S plus low-dose prednisone (group C) suffered serious relapse after 2-24 months. T/S induced long-term remission in > 50% of patients with initial phase WG; however, neither T/S alone nor T/S plus low-dose prednisone sustained remission in generalized WG.

Adult↗

Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

Adult↗

The effect of partial coating with hydroxyapatite on bone remodeling in relation to porous-coated titanium-alloy dental implants in the dog.

For inhibition of crestal bone resorption due to stress shielding and disuse atrophy, an hydroxyapatite (HA) plasma coating was added to the coronal portion of partially porous-coated endosseous dental implants. These implants, as well as control non-HA-coated implants were placed in healed mandibular premolar extraction sites in dogs for a 72-week period of function. Histological examination showed that both implant designs became securely fixed by bone ingrowth into the porous-coated apical region of the implants. The plasma-sprayed HA coating resulted in significantly greater bone height formation and maintenance next to the coronal portion of the implant compared with non-HA-coated implants of similar design. In addition, significant resorption of the 20-to-50-microns-thick plasma-sprayed HA coating occurred over the 18-month period of function.

Alloys↗

A clinical, radiographic, and histological evaluation of permucosal dental implants of dense hydroxylapatite in dogs.

A clinical, histological, and radiographic examination was performed on 77 permucosal dental implants, made of dense sintered hydroxylapatite: 34 solid cylinders and 43 hollow cylinders. The hollow cylinders were pre-compressed between two titanium caps. The implants were placed in partly edentulous mandibles of dogs, and were physiologically loaded. Healing was clinically and radiographically evaluated during a six-month to five-year period. At various times, implants with their surrounding tissues were removed and prepared for light and electron microscopy. All implants showed a good initial fit and were maintained in place without undercut or mechanical stabilization. After 18 months, 76% of the solid cylinders had fractured at the implant/bone junction due to fatigue. However, the submerged portions of the solid cylinders were preserved without clinical problems, and became entirely embedded in bone. The pre-stressed implants did not fracture, and 91% were functioning 24 months after placement. The average scores of pocket depths and gingival bleeding showed no significant differences between implants and surrounding natural teeth. Bone deposition occurred on the entire surface of the implant below the crest of the alveolar bone, and intimate bone contact was confirmed by electron microscopy. It was also observed that a layer of bone tissue was deposited on the implant surface in the permucosal area just above the alveolar bone level. Embedding of gingival fibers in this layer resulted in gingival attachment to the implant, comparable with that of natural teeth.

Alveolar Process↗