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Biomedical subjects

J Sohier

Publications and source records attributed to J Sohier.

At least 19 recordsLinked to original sources

Tailored release of TGF-beta1 from porous scaffolds for cartilage tissue engineering.

In view of cartilage tissue engineering, the possibility to prepare porous scaffolds releasing transforming growth factor-beta(1) (TGF-beta(1)) in a well controlled fashion was investigated by means of an emulsion-coating method. Poly(ether-ester) multiblock copolymers were used to prepare emulsions containing TGF-beta(1) which were subsequently applied onto prefabricated scaffolds. This approach resulted in defined porous structures (66%) with interconnected porosity, suitable to allow tissue ingrowth. The scaffolds were effectively associated with TGF-beta(1) and allowed to tailor precisely the release of the growth factor from 12 days to more than 50 days by varying the copolymer composition of the coating. An incomplete release was measured by ELISA, possibly linked to the rapid concentration decrease of the protein in solution. The released growth factor retained its biological activity as was assessed by a cell proliferation assay and by the ability of the released protein to induce chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. However, exact bioactivity quantification was rendered difficult by the protein concentration decrease during storage. Therefore, this study confirms the interest of poly(ether-ester) multiblock copolymers for controlled release of growth factors, and indicates that emulsion-coated scaffolds are promising candidates for cartilage tissue engineering applications requiring precise TGF-beta(1) release rates.

Animals↗

Dual release of proteins from porous polymeric scaffolds.

To create porous scaffolds releasing in a controlled and independent fashion two different proteins, a novel approach based on protein-loaded polymeric coatings was evaluated. In this process, two water-in-oil emulsions are forced successively through a prefabricated scaffold to create coatings, containing each a different protein and having different release characteristics. In a first step, a simplified three-layered system was designed with model proteins (myoglobin and lysozyme). Poly(ether-ester) multiblock copolymers were chosen as polymer matrix, to allow the diffusion of proteins through the coatings. The model system showed the independent release of the two proteins. The myoglobin release was tailored from a burst to a linear release still on-going after 60 days, while the lysozyme release rate was kept constant. Macro-porous scaffolds, with a porosity of 59 vol.%, showed the same ability to control the release rate of the model proteins independently. The relation between the coatings properties and their release characteristics were investigated with the use of a mathematical diffusion model based on Fick's second law. It confirmed that the multiple coated scaffolds are biphasic system, where each coating controls the release of the protein that it contains. This approach could be of value for tissue engineering applications.

Algorithms↗

Biodegradable poly(ether-ester) multiblock copolymers for controlled release applications: An in vivo evaluation.

Multiblock poly(ether-ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate segments were evaluated for their in vivo degradation and biocompatibility in order to establish a correlation with previously reported in vitro results. Porous polymer sheets were implanted subcutaneously for 32 weeks in rats. The degradation was monitored visually (histology), by molecular weight (GPC), and by copolymer composition (NMR). Substitution of the aromatic terephthalate units by aliphatic succinate units was shown to accelerate the degradation rate of the copolymers. Direct correlation of the in vivo and in vitro degradation of the porous implants showed a slightly faster initial molecular weight decrease in vivo. Besides hydrolysis, oxidation occurs in vivo due to the presence of radicals produced by inflammatory cells. In addition, the higher molecular weight plateau of the residue found in vivo indicated a higher solubility of the oligomers in the extracellular fluid compared to a phosphate buffer. Minor changes in the poly(ether-ester) compositions were noted due to degradation. Microscopically, fragmentation of the porous implants was observed in time. At later stages of degradation, macrophages were observed phagocytozing small polymer particles. Both in vitro cytotoxicity studies and histology on in vivo samples proved the biocompatibility of the poly(ether-ester)s.

Animals↗

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↗

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↗

[Weber-Christian syndrome and chronic pancreatitis (author's transl)].

The authors describe a case of cytosteatonecrosis associated with chronic pancreatitis. Clinical, biological (amylasemia and amylasuria) and radiological (arteriography) signs of pancreatic disease are noticed as well as important radiological lesions of the limbs. The cutaneous lesions are hypodermic nodules located on the lower limbs with swelling of the right big toe and a cutaneous abrasion.

Bone Diseases↗

The lichen planus like and sclerotic phases of the graft versus host disease in man: an ultrastructural study of six cases.

Skin biopsies from 6 patients with chronic graft-versus-host disease (GVHD) were studied ultrastructurally. The 6 patients experienced an early lichenoid phase 65-135 days after the graft and 3 of them progressed to a late sclerotic phase 200-340 days after the grafting Damage to the basal membrane and to the keratinocytes of the basal layer and low spinous layers, and presence of epidermal regenerative cells were features common to the lichenoid phase of chronic GVHD and idiopathic lichen planus. The late sclerotic phase of GVHD with persistence of basal cell injury, normal periodicity and structure of the collagen fibres and numerous active fibroblasts in the upper third of the dermis were findings that distinguished GVHD from scleroderma. Satellite cell necrosis, i.e. lymphocyte satellites of necrotic keratinocyte, was observed in the two phases of chronic GVHD. Thus at the ultrastructural level the early phase of chronic GVHD mimics lichen planus, but the late sclerotic phase is distinct from scleroderma.

Adult↗

[Cutaneous manifestations of graft versus host disease (author's transl)].

Skin is a target organ for Graft v Host Reaction (GvHR). Cutaneous changes sometimes are the first symptoms for GvHR. They offer the opportunity for its early recognition. They include: -- A primarily acute phase, as red maculopapular rash, on face, palms and soles, which can spread over large areas, resembling scarlatiniform rash. Some courses have resulted in severe epidermal necrolysis similar to Lyell syndrome. -- A chronic phase, described with a variable time of onset after the acute episode. Two stages have been recognised: -- the early chronic phase has a clinical and histological picture similar to Lichen Planus, a frequent dermatosis which is thought to be the result of a chronic immune injury against epidermis. As early phase is fading, an atrophic aspect of the skin may develop, whose severe type is described as Poïkiloderma. -- The late chronic phase, in which densification of dermal collagen is become the essential features. In some patients, sclerotic changes develop, which are resembling to scleroderma ones. The cutaneous manifestations of GvH Disease can be responsible for considerable morbidity, mortality and sequelles. They may serve as a biological model for several skin diseases.

Acute Disease↗

[Ultrastructural similarities between the planus-like reaction of the graft versus host disease and the idiopathic lichen planus (author's transl)].

An ultrastructural study was performed on skin biopsies of eight patients with lichenoid eruption of chronic graft-versus-host disease (GVHD). The lichenoid eruption is similar to idiopathic lichen planus with the injury of the basal cells, the distribution of the numerous colloid bodies, and the presence of regenerative cells. Lymphocytes satellites of injured keratinocytes were observed in those lichenoid eruptions, as well as in the acute phase of GVHD. The numerous mast cells in the lichenoid eruption of GVHD may be related to the connective tissue changes of the patients progressing to a late sclerotic phase of chronic GVHD.

Adult↗

[Sezary syndrome with serum monoclonal immunoglobulin. Absence of detectable shared idiotype between the monoclonal immunoglobulin and membrane structures of the Sezary cells (author's transl)].

In a case of Sezary syndrome with monoclonal serum immunoglobulin (IgM kappa) haematological investigations and a study of lymphocyte membrane markers failed to demonstrate any proliferation of B-lymphocytes. In order to test the hypothesis that the T-cells of Sezary syndrome and the B-cells producing the monoclonal immunoglobulin derived from the same stem cells and belonged to the same clone, an antiserum specific for the idiotype determinants of the IgM was used to detect by membrane immunofluorescence the possible presence in Sezary cells of surface receptors containing these determinants. The results were negative. The significance of the association--probably relatively too frequent to be fortuitous--between T-lymphocyte proliferation and monoclonal serum immunoglobulin therefore remains uncertain.

B-Lymphocytes↗

Bone marrow transplantation in Fanconi anaemia.

Five patients with Fanconi anaemia have been treated by bone marrow transplantation from HLA identical donors. Only one patient survived for more than 3 years. She is now perfectly healthy with complete haematological reconstitution with chimaerism and disparition of chromosomal abnormalities. In contrast, four patients died of acute severe GVHD soon after grafting. In addition, all had signs of severe cyclophosphamide toxicity. This evolution could be explained by a special sensitivity of FA cells to alkylating agents and may indicate the need to modify the conditioning regimen in FA patients.

Anemia, Aplastic↗

[Photosensitivity and disturbances of tryptophan metabolism (kynurenin pathway) (author's transl)].

We studied a bullous photodermatosis recurring for two years in a old woman. The eruption was diagnosed as a pellagra-like syndrome on tryptophan loading test disorders without any other cause of sun sensitivity. The static and dynamic metabolic investigation was centered on tryptophan and vitaminic coenzymes which mediate catabolic reactions. The defect are located on the kinurenin pathway. The discussion analyses the possible relations between the dermatosis and the biological disturbances observed.

Aged↗