ABSTRACT
Cryogels made of components of natural extracellular matrix components are potent biomaterials for bioengineering and regenerative medicine. Human dermal fibroblasts are key cells for tissue replacement during wound healing. Thus, any biomaterial for wound healing applications should enable growth, differentiation and matrix synthesis by these cells. Cryogels are highly porous scaffolds consisting of a network of interconnected pores. Here, we used a novel group of cryogels generated from acrylated hyaluronan where the polymerization was initiated by accelerated electrons (E-beam). This novel procedure omits any toxic polymerization initiators and results in sterile, highly elastic scaffolds with adjustable pore size, excellent swelling and low flow resistance properties. We show that these cryogels are effective 3D-substrates for long-term cultures of human dermal fibroblasts in vitro. The cells proliferate for at least 28days throughout the cryogels and deposit their own matrix in the pores. Moreover, key modulators of dermal fibroblasts during wound healing like TGFß and PDGF efficiently stimulated the expression of wound healing-relevant genes. In conclusion, electron beam initiated cryogels of acrylated hyaluronan represent a functional and cell compatible biomaterial that could be adapted for special wound healing applications by further functionalization.
Subject(s)
Acrylates/pharmacology , Cryogels/pharmacology , Electrons , Extracellular Matrix/metabolism , Fibroblasts/drug effects , Hyaluronic Acid/pharmacology , Acrylates/chemistry , Biocompatible Materials , Cell Proliferation/drug effects , Cryogels/chemical synthesis , Dermis/cytology , Dermis/metabolism , Elasticity , Extracellular Matrix/chemistry , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Hyaluronic Acid/chemistry , Male , Platelet-Derived Growth Factor/pharmacology , Polymerization , Porosity , Primary Cell Culture , Tissue Engineering , Tissue Scaffolds , Transforming Growth Factor beta/pharmacologyABSTRACT
Inflammatory bowel disease (IBD) has a definite genetic component as documented by epidemiological and linkage evidence. It shows an earlier onset of disease in children of affected patients than in their parents. This has lead to speculations about genetic anticipation in this disorder. 2,007 IBD patients with sporadic disease and 472 multiplex familial cases (including 103 affected parents and 99 children of affected patients) were evaluated with a multi-item questionnaire as part of a study of inflammatory bowel disease genetics. The Mann-Whitney U-test and the general linear model were used for analysis. Clinical characteristics such as presence of fistulae, stenoses, extraintestinal manifestations, and other parameters, which are related to the severity of the disease, were found to be similar between familial and sporadic cases of IBD (corrected P > or = 0.31 for all tests). The mean-age-of onset in children of affected patients was 19.4 years earlier than in their parents. However, the age of the parental cohort was significantly higher (27 years) and the diagnostic interval also longer (1.7 years). If these confounders are corrected in a general linear model, no significant difference is evident for the age-of-onset between the groups (P > or = 0.52). There is no evidence for genetic anticipation in inflammatory bowel disease. The absence of genetic anticipation is consistent with the clinical similarity of familial and sporadic inflammatory bowel disease. This finding justifies the primary genetic analysis of familial disease under the assumption that their genetic background will be representative for all presentations of IBD.
Subject(s)
Anticipation, Genetic , Inflammatory Bowel Diseases/genetics , Adult , Age of Onset , Cohort Studies , Confounding Factors, Epidemiologic , Data Interpretation, Statistical , Germany/epidemiology , Humans , Infant , Infant, Newborn , Inflammatory Bowel Diseases/epidemiology , Surveys and Questionnaires , Trinucleotide Repeat ExpansionABSTRACT
In mature male rats both estradiol administration as well as castration had a striking suppressive effect on the hepatic activity of the microsomal ethanol-oxidizing system, whereas alcohol dehydrogenase activity was increased under these experimental conditions. The castration effects on the activities of the alcohol-metabolizing enzymes could be completely prevented by the administration of testosterone. Therefore, these results indicate the sex-dependent nature of the hepatic microsomal ethanol-oxidizing system and alcohol dehydrogenase.
