Biomanufacturing integrates life science and engineering fundamentals to produce biocompatible products enhancing the quality of life. The state-of-the-art of this rapidly evolving manufacturing sector is presented and discussed, in particular the additive electrical, chemical and physical processes currently being applied to produce synthetic and biological parts. This fabrication strategy is strongly material-dependent, so the main classes of biomaterials are detailed. It is explained the potential to process composite materials combining synthetic and biological materials, such as cells, proteins and growth factors, as well the interdependences between materials and processes. The techniques commonly used to increase the bioactivity of clinical implants and improve the interface characteristics between biological tissues and implants are also presented.

Biomedical production of implants by additive electro-chemical and physical processes

Inertial microfluidics has recently drawn wide attention as an efficient, high-throughput microfluidic cell separation method. However, the achieved separation resolution and throughput, as well as the issues with cell dispersion due to cell-cell interaction, have appeared to be limiting factors in the application of the technique to real-world samples such as blood and other biological fluids. In this paper, we present a novel design of a spiral inertial microfluidic (trapezoidal cross-section) sorter with enhanced separation resolution and demonstrate its ability in separating/recovering polymorphonuclear leukocytes (PMNs) and mononuclear leukocytes (MNLs) from diluted human blood (1-2% hematocrit) with high efficiency (>80%). PMNs enriched by our method also showed negligible activation as compared to original input sample, while the conventional red blood cell (RBC) lysis method clearly induced artificial activation of the sensitive PMNs. Therefore, our proposed technique would be a promising alternative to enrich/separate sensitive blood cells for therapeutic or diagnostic applications.

Separation of leukocytes from blood using spiral channel with trapezoid cross-section.

The cell seeding density and spatial distribution in a 3-D scaffold are critical to the morphogenetic development of an engineered tissue. A dynamic depth-filtration seeding method was developed to improve the initial cell seeding density and spatial distribution in 3-D nonwoven fibrous matrices commonly used as tissue scaffolds. In this work, trophoblast-like ED27 cells were seeded in poly(ethylene terephthalate) (PET) matrices with various porosities (0.85-0.93). The effects of the initial concentration of cells in the suspension used to seed the PET matrix and the pore size of the matrix on the resulting seeding density and subsequent cell proliferation and tissue development were studied. Compared to the conventional static seeding method, the dynamic depth-filtration seeding method gave a significantly higher initial seeding density (2-4 x 10(7) vs 4 x 10(6) cells/cm3), more uniform cell distribution, and a higher final cell density in the tissue scaffold. The more uniform initial cell spatial distribution from the filtration seeding method also led to more cells in S phase and a prolonged proliferation period. However, both uniform spatial cell distribution and the pore size of the matrices are important to cell proliferation and morphological development in the seeded tissue scaffold. Large-pore matrices led to the formation of cell aggregates and thus might reduce cell proliferation. The dynamic depth-filtration seeding method is better in providing a higher initial seeding density and more uniform cell distribution and is easier to apply to large tissue scaffolds. A depth-filtration model was also developed and can be used to simulate the seeding process and to predict the maximum initial seeding densities in matrices with different porosities.

Effects of filtration seeding on cell density, spatial distribution, and proliferation in nonwoven fibrous matrices.

Surface strategies for control of neuronal cell adhesion: A review

Preparation and characterization of chemical gradient surfaces and their application for the study of cellular interaction phenomena

https://ris.utwente.nl/ws/files/6718197/Bruil95mechanisms.pdf

The mechanisms of leukocyte removal by filtration

A method for removing leukocytes from a leukocyte-­containing suspension by passing a leukocyte-containing suspension over a filter unit containing a filter comprising a continuous porous structure, and obtaining a leukocyte-poor liquid, whereby a continuous porous structure or a combination of porous structures is used having a pore gradient with decreasing pore size in the direction of the flow of the suspension.

A method for the removal of leukocytes from a leukocyte-containing suspension and filter unit for use with the method

https://ris.utwente.nl/ws/files/6652967/Bruil92in.pdf

In vitro leucocyte adhesion to modified polyurethane surfaces. I. Effect of ionizable functional groups

As part of a study on the mechanisms of leukocyte filtration, the influence of pore size distribution on filter efficiency was investigated. Conventional leukocyte filters are not suitable for model studies, as these filters are composed of tightly packed synthetic fibers, with a poorly defined porous structure. Therefore, open cellular polyurethane membranes with pore size distributions varying from approximately 15 to 65 m were prepared. Filtration experiments with stacked packages of these membranes showed that leukocytes are best removed (>99%) by filters with a pore size distribution of 11-19 m. These pore sizes approach the size of leukocytes (6-12 m). However, due to fast clogging, blood flow through these filters is rapidly reduced, which results in a low filter capacity. With an asymmetric membrane filter, in which the pore size decreases from about 65 to 15 m in the direction of blood flow, both moderate removal of leukocytes (>80%) and maintenance of flow (0.2 mL/s) are obtained. This results in efficient leukocyte removal. From cell analysis of both filtrate and filter, it is concluded that adhesion rather than sieving is the major filtration mechanism. Thus, further optimization of the filter may be achieved by surface modification.

/pdf/asymmetric-membrane-filters-for-the-removal-of-leukocytes-3p1b6r3smm.pdf

Asymmetric membrane filters for the removal of leukocytes from blood

https://ris.utwente.nl/ws/files/6652141/Bruil94invitro.pdf

Anton Bruil

Papers

The mechanisms of leukocyte removal by filtration

A method for the removal of leukocytes from a leukocyte-containing suspension and filter unit for use with the method

In vitro leucocyte adhesion to modified polyurethane surfaces. I. Effect of ionizable functional groups

Asymmetric membrane filters for the removal of leukocytes from blood

In vitro leukocyte adhesion to modified polyurethane surfaces: II. Effect of wettability