Paul Nieuwenhuis

Bio: Paul Nieuwenhuis is an academic researcher from University of Groningen. The author has contributed to research in topics: Antigen & Germinal center. The author has an hindex of 44, co-authored 159 publications receiving 7217 citations.

Glutaraldehyde as a crosslinking agent for collagen-based biomaterials

Abstract: The formation of Schiff bases during crosslinking of dermal sheep collagen (DSC) with glutaraldehyde (GA), their stability and their reactivity towards GA was studied. All available free amine groups had reacted with GA to form a Schiff base within 5 min after the start of the reaction under the conditions studied (0.5% (w/w) GA). Before crosslinks are formed the hydrolysable Schiff bases initially present were stabilized by further reaction with GA molecules. An increase in shrinkage temperature (Ts) from 56°C for non-crosslinked DSC (N-DSC) to 78°C for GA crosslinked DSC (G-DSC) was achieved after crosslinking for 1 h. From the relationship between the free amine group content and the Ts during crosslinking it was concluded that higher GA concentrations and longer reaction times will result in the introduction of pendant-GA-related molecules rather than crosslinks. After 24 h crosslinking an average uptake of 3 GA molecules per reacted amine group was found. No increase in the tensile strength of the materials was observed after crosslinking, which may be a result of formation of crosslinks within the fibres rather than in between fibres. Aligning of the fibres by applying a pre-strain to the samples and subsequent crosslinking yielded materials with an increased tensile strength.

Origin of neointimal endothelium and alpha-actin-positive smooth muscle cells in transplant arteriosclerosis.

Abstract: The development of transplant arteriosclerosis (TA) is today's most important problem in clinical organ transplantation. Histologically, TA is characterized by perivascular inflammation and progressive intimal thickening. Current thought on this process of vascular remodeling assumes that neointimal vascular smooth muscle (VSM) cells and endothelium in TA are graft-derived, holding that medial VSM cells proliferate and migrate into the subendothelial space in response to signals from inflammatory cells and damaged graft endothelium. Using MHC class I haplotype-specific immunohistochemical staining and single-cell PCR analyses, we show that the neointimal alpha-actin-positive VSM cells in rat aortic or cardiac allografts are of recipient and not of donor origin. In aortic but not in cardiac allografts, recipient-derived endothelial cells (ECs) replaced donor endothelium. Cyclosporine treatment prevents neointima formation and preserves the vascular media in aortic allografts. Recipient-derived ECs do not replace graft endothelium after cyclosporine treatment. We propose that, although it progresses beyond the needs of functional repair, TA reflects the activity of a normal healing process that restores vascular wall function following allograft-induced immunological injury.

Long-Circulating and Target-Specific Nanoparticles: Theory to Practice

Abstract: The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

Molecular Regulation of Vascular Smooth Muscle Cell Differentiation in Development and Disease

Abstract: The focus of this review is to provide an overview of the current state of knowledge of molecular mechanisms/processes that control differentiation of vascular smooth muscle cells (SMC) during normal development and maturation of the vasculature, as well as how these mechanisms/processes are altered in vascular injury or disease. A major challenge in understanding differentiation of the vascular SMC is that this cell can exhibit a wide range of different phenotypes at different stages of development, and even in adult organisms the cell is not terminally differentiated. Indeed, the SMC is capable of major changes in its phenotype in response to changes in local environmental cues including growth factors/inhibitors, mechanical influences, cell-cell and cell-matrix interactions, and various inflammatory mediators. There has been much progress in recent years to identify mechanisms that control expression of the repertoire of genes that are specific or selective for the vascular SMC and required for its differentiated function. One of the most exciting recent discoveries was the identification of the serum response factor (SRF) coactivator gene myocardin that appears to be required for expression of many SMC differentiation marker genes, and for initial differentiation of SMC during development. However, it is critical to recognize that overall control of SMC differentiation/maturation, and regulation of its responses to changing environmental cues, is extremely complex and involves the cooperative interaction of many factors and signaling pathways that are just beginning to be understood. There is also relatively recent evidence that circulating stem cell populations can give rise to smooth muscle-like cells in association with vascular injury and atherosclerotic lesion development, although the exact role and properties of these cells remain to be clearly elucidated. The goal of this review is to summarize the current state of our knowledge in this area and to attempt to identify some of the key unresolved challenges and questions that require further study.