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Biomedical subjects

J M Schakenraad

Publications and source records attributed to J M Schakenraad.

At least 19 recordsLinked to original sources

In vivo and in vitro degradation of poly[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL], and the implications for the use in nerve reconstruction.

Nerve guides can be used for the reconstruction of peripheral nerve defects. After serving their function, nerve guides should degrade. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] degrades completely within 1 year without the formation of a slow degrading crystalline fraction. Although the tensile strength (TS) of a p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guide is negligible after 2 months, nerve regeneration across a 1-cm gap in the sciatic nerve of the rat is faster and qualitatively better than after reconstruction using autologous nerve grafts. During degradation p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] swells, especially during the first 3 months. This can have a negative influence on the regenerating nerve. p[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL] nerve guides could only be used in the clinical situation in case of short nerve gaps (several mm) in small nerves (for instance digital nerves). Refinements will be needed to successfully reconstruct longer nerve gaps (several cm).

Animals↗

Long-term evaluation of functional nerve recovery after reconstruction with a thin-walled biodegradable poly (DL-lactide-epsilon-caprolactone) nerve guide, using walking track analysis and electrostimulation tests.

This study was performed to evaluate the long-term functional nerve recovery after reconstruction of a 10-mm gap in the sciatic nerve of the rat, with a thin-walled nerve guide, composed of a biodegradable copolymer of DL-lactide and epsilon-caprolactone [p(DLLA-epsilon-CL)]. To evaluate both motor and sensory nerve recovery, walking track analysis and electrostimulation tests were carried out after implantation periods ranging from 3 to 52 weeks postoperatively. The first signs of both motor and sensory nerve recovery could be observed after 5 weeks. After 15 weeks, 70% of the sciatic function and 90% of the sensory nerve function had been recovered. After this period, the sciatic function index (SFI) did not improve further, whereas the sensory nerve function appeared to return to normal. When the results of the SFI measurements, minus those obtained from rats with severe automutilation, are extrapolated, further improvement of the SFI might be expected after 52 weeks. The fact that 100% sensory nerve recovery was obtained, as measured by the electrostimulation test, could be explained by sensory reinnervation from surrounding areas. The SFI was not fully reestablished because automutilation had a great impact on the use of walking track assessment.

Animals↗

Functional assessment of sciatic nerve reconstruction: biodegradable poly (DLLA-epsilon-CL) nerve guides versus autologous nerve grafts.

The aim of this study was to compare functional nerve recovery after reconstruction with a biodegradable p(DLLA-epsilon-CL) nerve guide filled with modified denatured muscle tissue (MDMT), or an autologous nerve graft. We evaluated nerve recovery using walking track analysis (measurement of the sciatic function index [SFI]) and electrostimulation tests. Functional nerve recovery after reconstruction with a biodegradable p(DLLA-epsilon-CL) nerve guide filled with MDMT was faster when compared with nerve reconstruction using an autologous nerve graft. We conclude that in case of a short nerve gap in the rat, reconstruction can best be carried out using a p(DLLA-epsilon-CL) biodegradable nerve guide filled with MDMT.

Absorbable Implants↗

Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration.

The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated using light microscopy, immunohistochemistry and cryo-scanning electron microscopy. Sample C showed the most open extracellular matrix, whilst collagen type IV and laminin (in the basal lamina) could still be observed using immunohistochemistry. An in vivo pilot study showed that the first signs of functional nerve recovery and axon regeneration could be observed after 3 weeks of implantation. We conclude that sample C has the most open structure and leads to good nerve regeneration and functional nerve recovery.

Animals↗

Biocompatibility of a novel tissue connector for fixation of tracheostoma valves and shunt valves.

Rehabilitation after laryngectomy often includes the use of a shunt valve and a tracheostoma valve to restore voice. To improve the fixation method of these valves, a new tissue connector has been developed, basically consisting of a ring that will be integrated into surrounding tracheal soft tissue. The valves can be placed in the ring. To test the principle of the tissue connector, a prototype consisting of a subcutaneous polypropylene mesh and a percutaneous titanium stylus was implanted into the backskin of 10 rats by a two-stage surgical procedure. We reasoned that if a firm connection can be realized with the skin, a firm connection with the trachea will also be possible. The subcutaneous part was implanted first, followed by the percutaneous part after 6 weeks. The complete tissue connector with surrounding tissue was removed 8 weeks later and examined histologically. The principle of the new tissue connector proved to be effective: hardly any epithelial downgrowth appeared, and adhesion of soft tissue was demonstrated. No infection or severe inflammation reaction was detected. The tissue connector seems appropriate for its intended use.

Administration, Cutaneous↗

Long-term evaluation of degradation and foreign-body reaction of subcutaneously implanted poly(DL-lactide-epsilon-caprolactone).

The aim of this study was to evaluate the degradation and foreign-body reaction of poly(DL-lactide-epsilon-caprolactone) (PLA85CL50) bars. This specific biomaterial is used for the construction of nerve guides, which can be used in the reconstruction of short nerve gaps. Subcutaneously implanted PLA85CL50 bars were harvested after implantation periods ranging from 3 to 12 months and evaluated for the rate of degradation and the degree of foreign-body reaction. It was observed that this copolymer degraded completely within 12 months and that no lactide or epsilon-caprolactone crystals were formed. Furthermore, we conclude that the foreign-body reaction of PLA85CL50 is very mild. These properties make the amorphous copolymer of DL-lactide and epsilon-caprolactone (50:50) suitable for the construction of nerve guides.

Administration, Cutaneous↗

Cytotoxic, allergic and genotoxic activity of a nickel-titanium alloy.

The nearly equiatomic nickel-titanium (NiTi) alloy is known for its shape memory properties. These properties can be put to excellent use in various biomedical applications, such as wires for orthodontic tooth alignment and osteosynthesis staples. The aim of this study was to evaluate the short-term biological safety of the NiTi alloy. We carried out an end-point dilution minimal essential medium (MEM) extract cytotoxicity test, a guinea-pig sensitization test and two genotoxicity tests: the Salmonella reverse mutation test and the chromosomal aberration test. The NiTi alloy showed no cytotoxic, allergic or genotoxic activity, similar to the clinical reference control material AISI 316 LVM stainless steel. This promising biological behaviour was most likely due to a minimal release of ions and in that way a reflection of the good corrosion resistance of the NiTi alloy. Given these very good results, together with the good tissue compatibility as shown in several implantation studies in the literature, the NiTi alloy can be regarded as a biologically safe implant material with many promising clinical applications.

Alloys↗

Evaluation of functional nerve recovery after reconstruction with a new biodegradable poly (DL-lactide-epsilon-caprolactone) nerve guide.

The aim of this study was to evaluate functional nerve recovery following reconstruction of a 1 cm gap in the sciatic nerve of a rat, using a new biodegradable p (DLLA-epsilon-CL) nerve guide. To evaluate both motor and sensory nerve recovery, walking track analysis and electrostimulation tests were carried out after implantation periods, ranging from 3 to 15 weeks post-operatively. The first signs of functional nerve recovery were observed after 3 weeks. After 15 weeks, 70% of the motor- and 90% of the sensory nerve function was re-established. Return of nerve function was better, in comparison with results from other studies. This study demonstrated successful functional nerve recovery after the reconstruction of a 1 cm nerve gap with a biodegradable p(DLLA-epsilon-CL) nerve guide.

Animals↗

Light-microscopic and electron-microscopic evaluation of short-term nerve regeneration using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide.

The aim of this study was to evaluate short-term peripheral nerve regeneration across a 10-mm. gap, using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide, with an internal diameter of 1.5 mm and a wall thickness of 0.30 mm. To do so, we evaluated regenerating nerves using light microscopy, transmission electron microscopy and morphometric analysis after implantation of 12-mm nerve guides in the sciatic nerve of the rat. Evaluation times ranged from 3-10 weeks. Three weeks after reconstruction, myelinated nerve fibers could be observed in the distal nerve stump. Ten weeks after reconstruction, the regenerating nerves already resembled normal nerves. In conclusion, we show that poly(DL-lactide-epsilon-caprolacton) nerve guides can be successfully applied in the reconstruction of severed nerves in the rat model. Furthermore, we have observed the fastest nerve regeneration described thus far, after reconstruction using a biodegradable nerve guide.

Animals↗

Evaluation of functional nerve recovery after reconstruction with a poly (DL-lactide-epsilon-caprolactone) nerve guide, filled with modified denatured muscle tissue.

The aim of this study was to compare the speed of functional nerve recovery after reconstruction with a biodegradable p(DLLA-epsilon-CL) nerve guide, as filled with either modified denatured muscle tissue (MDMT) or phosphate-buffered saline (PBS). To evaluate both motor and sensory nerve recovery, walking-track analysis and electrostimulation tests were carried out after implantation periods, ranging from 3-15 weeks. Functional nerve recovery after reconstruction of a 15-mm nerve gap, with a biodegradable p(DLLA-epsilon-CL) nerve guide filled with modified denatured muscle tissue, was slightly faster, compared with nerve reconstruction of a 10-mm gap with a biodegradable p(DLLA-epsilon-CL) nerve guide filled with PBS. We conclude that our experiments have demonstrated that the use of MDMT increases the speed of recovery after reconstruction of a nerve gap with a p(DLLA-epsilon-CL) biodegradable nerve guide. Furthermore, the use of MDMT might open perspectives for repair of longer nerve gaps.

Animals↗

Poly(DL-lactide-epsilon-caprolactone) nerve guides perform better than autologous nerve grafts.

The aim of this study was to compare the speed and quality of nerve regeneration after reconstruction using a biodegradable nerve guide or an autologous nerve graft. We evaluated nerve regeneration using light microscopy, transmission electron microscopy and morphometric analysis. Nerve regeneration across a short nerve gap, after reconstruction using a biodegradable nerve guide, is faster and qualitatively better, when compared with nerve reconstruction using an autologous nerve graft. Therefore, we conclude that in the case of a short nerve gap (1 cm), reconstruction should be carried out using a biodegradable nerve guide constructed of a copolymer of DL-lactide and epsilon-caprolactone.

Analysis of Variance↗

Biological performance of a degradable poly(lactic acid-epsilon-caprolactone) nerve guide: influence of tube dimensions.

One of the ways to reconstruct a nerve defect is to use a biodegradable nerve guide. The aim of this study was to establish a nerve guide constructed of an amorphous copolymer of lactic acid-caprolactone. A pilot study was set up to elucidate the effect of the tube dimensions on nerve regeneration. Four types of nerve guides, with internal diameters ranging from 1.12-1.23 mm and wall thicknesses ranging from 0.34-0.68, were tested for this purpose. We evaluated the biodegradation, foreign body reaction and nerve regeneration by light microscopy, after three different implantation times (1, 2, and 3 months). After 2 months, we observed that all types of nerve guides had changed from a transparent to an opaque and swollen state, and that they had lost their strength. The foreign body reaction was characterized by the presence of giant cells and fibroblasts surrounding the degrading nerve guide. From this pilot study, we conclude that nerve guide type 1, with an internal diameter of 1.23 mm and a wall thickness of 0.34 mm, can ensure nerve regeneration in the case of a 1-cm gap in the sciatic nerve of the rat. Nerve guides types 3 and 4, with relatively small lumens, show nerve compression due to a more pronounced swelling of the degrading tube.

Animals↗

The influence of surface morphology and wettability on the inflammatory response against poly(L-lactic acid): a semi-quantitative study with monoclonal antibodies.

In this study, the influence of surface morphology and wettability of both degradable and nondegradable polymer films on the inflammatory response after subcutaneous implantation in the rat was investigated. Degradable non-porous, porous, and "combi" (porous with a nonporous layer on one side) poly(L-lactic acid) (PLLA) films and nondegradable polytetrafluoroethylene (PTFE) and (porous) expanded PTFE (e-PTFE) were used. Contact angles measurements indicate that PLLA is more hydrophillic than PTFE. Assessment of the inflammatory response was performed after various periods of implantation (up till 180 days), with both conventional light microscopy and immunohistochemistry using monoclonal antibodies (mAbs). The inflammatory response observed initially can largely be considered as part of the wound healing reaction, and up till day 40 the inflammatory response against PLLA was minimally more intense than against PTFE (porous as well as nonporous). From day 40 on, the PLLA films provoke a more intense inflammatory response as compared to the PTFE films. Both porous PLLA and the porous side of the "combi" PLLA film provoke a more intense inflammatory response than nonporous PLLA and the nonporous side of the "combi" PLLA film, respectively. In general, PTFE and e-PTFE films provoke an inflammatory response which is minimally more intense than the one provoked by the sham operation. Almost no ingrowth of tissue was observed in the porous e-PTFE films. In contrast, there was abundant tissue ingrowth in and an inflammatory response against porous PLLA. It can be concluded that biodegradable PLLA films provoke a more intense inflammatory response than nondegradable PTFE films. Also, porosity enhances the inflammatory response. However, porosity enhances the inflammatory response only when the wettability of a biomaterial permits cellular ingrowth.

Animals↗

Adhesion and spreading of human skin fibroblasts on physicochemically characterized gradient surfaces.

In this study, adhesion and spreading of human skin fibroblasts on gradient surfaces of dichlorodimethylsilane (DDS) coupled to glass was investigated. Gradient surfaces were prepared by the diffusion technique and characterized by the Wilhelmy plate technique and characterized by the Wilhelmy plate technique for their wettability and by scanning x-ray photoelectron spectroscopy for their chemical surface composition. A linear relation between the gradient length, based on advancing water contact angles, and the square root of the diffusion time of DDS was observed. XPS analysis and the cellular experiments were carried out on gradient surfaces prepared using a diffusion time of 3 h. A continuously varying chemical composition with Si/O elemental surface concentration ratio being highest on the hydrophobic end of the gradient surfaces. In the presence of serum proteins, human skin fibroblasts seeded on these gradient surfaces showed a preferential adhesion onto the steepest part of the gradient, probably due to an optimal local wettability and/or local chemistry. Furthermore, it was shown that the spread area of human fibroblasts increased over the length of the gradient surface when going from the hydrophobic to the hydrophilic end. Summarizing, this study shows that the use of gradient surfaces to study cellular responses to materials surface properties, like wettability, yields more-convincing conclusions than the use of a variety of materials with different wettabilities due to the control of the specific surface chemistry of gradient surfaces.

Cell Adhesion↗

Influence of luminal pore size on the patency rate and endothelialization of polymeric microvenous prostheses.

In microvenous prosthetic surgery a continuous search for better patency rates is necessary to enable a clinical application. In this search for better patencies, modifications in the wall structure are being made. Directions found in the literature suggest that pore size plays an important role in achieving better patencies. Thus far, no study has been conducted to evaluate the influence of pore size on the patency rate of polyurethane microvenous prostheses. Since polyurethane is known to yield good patency rates, we conducted this study in which we compared different luminal pore sizes with regard to patency. Pore size varied from 0.6 to 20 microns in microvenous polyurethane-based prostheses (length 5-6 mm, internal diameter 1 mm). The results showed a favorable patency rate in the pore sizes larger than 5.0 microns (patency 75%) when compared to pore sizes smaller than 2.0 microns (patency 50%). This study demonstrates that microvenous polyurethane-based prostheses with a luminal pore size larger than 5.0 microns may yield better patency rates than prostheses with a luminal pore size smaller than 5.0 microns. Further studies are currently being performed to elucidate the very reasons for this effect.

Animals↗

Degradation and intrahepatic compatibility of albumin-heparin conjugate microspheres.

The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by proteolytic enzymes such as trypsin, proteinase K and lysosomal enzymes. The degradation rate was inversely related to the cross-link density of the microspheres. After intrahepatic administration of AHCMS, cross-linked with 0.5% glutaraldehyde, to male Wag/Rij rats by injection into a mesenteric vein (intravenoportal: i.v.p.), the microspheres were entrapped in the hepatic vascular system. The AHCMS were entrapped within terminal portal veins predominantly at the periphery of the liver. The AHCMS were degraded by cellular enzymatic processes within 2 wk after injection, with a half life of approximately 1 d. Biocompatibility of AHCMS and adriamycin-loaded AHCMS was evaluated by histological assessment of the mitotic activity of liver parenchyma and inflammatory response, and by determination of liver damage marker enzymes during 4 wk after administration. Liver damage marker enzymes were not increased compared with controls, nor were adverse effects observed upon histological examination. There was no difference in response between empty and adriamycin-loaded AHCMS.

Albumins↗

Fluid shear induced endothelial cell detachment from glass--influence of adhesion time and shear stress.

In this study, human umbilical vein and human saphenous vein endothelial cells were seeded on glass and exposed to fluid shear in a parallel-plate flow chamber. Cell retention, morphology and migration were studied as a function of shear stress and of adhesion time prior to exposure to shear. Three-hour and 24-h adhesion times gave rise to comparable cell retention values after 2 h of flow for both cell types. Cell retention decreased from 85 to 20% as shear stress increased from 88 to 264 dynes cm-2 (8.8 to 26 Pa). Mean spreading areas decreased after the onset of flow, but subsequently stabilized to plateau values, which were smaller at higher shear stresses. Shape factors increased faster to higher values as cells were exposed to higher shear stresses, without any obvious preference in orientation of the cells with respect to the direction of flow. Migration was unidirectional with flow and linear with time. Migration was faster for cells which had adhered for 24 h than for cells which had adhered for 3 h and was accompanied by the presence of fibrillar structures left behind on the surface upstream of migrating cells. It is concluded that after 3 h adhesion to glass, cells have adhered with an adhesion strength that does not substantially increase during the next 21 h. However, during this time changes in cell-substratum interactions seem to occur judging by the differences in, e.g., migration rates.

Blood Vessel Prosthesis↗

Reherniation after repair of the abdominal wall with expanded polytetrafluoroethylene.

Defects of the abdominal wall that are not amendable to primary closure have to be bridged by synthetic materials. The use of a nonabsorbable expanded polytetrafluoroethylene (ePTFE) soft-tissue patch is advocated for this purpose. To investigate the suitability of the ePTFE patch, abdominal wall defects in 30 rats were repaired with ePTFE and compared with polypropylene (PP) mesh. Herniations and adhesions were scored, qualitatively and quantitatively, eight weeks after implantation and the patches were histologically examined. Herniations, all observed at the fascia and patch interface, were significantly more frequent in abdominal wall defects repaired with ePTFE (60 percent) than with PP (zero percent) (p < 0.001, chi-square test). Adhesion formation was less frequently found in rats treated with ePTFE and adhesions were less strongly attached. Histologic examination revealed no ingrowth of fibro-collagenous tissue into the ePTFE patch, whereas the PP mesh was completely incorporated into fibrocollagenous tissue, which was continuous with the adjacent fascia. We conclude that this study confirms our clinical experience that reherniations at the fascia and patch interface in abdominal wall defects closed with an ePTFE soft-tissue patch are the result of insufficient ingrowth of fibrocollagenous tissue into the patch, which results in an insufficient anchorage of the patch to the fascia.

Abdominal Muscles↗