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Precision-porous templated scaffolds of varying pore size drive dendritic cell activation.

ABSTRACT: Scaffold based systems have shown significant potential in modulating immune responses in vivo. While there has been much attention on macrophage interactions with tissue engineered scaffolds for tissue regeneration, fewer studies have looked at the effects of scaffold design on the response of immune cells-that is, dendritic cells (DCs). Here, we present the effects of varying pore size of poly (2-hydroxyethyl methacrylate) (pHEMA) and poly(dimethylsiloxane) (PDMS, silicone) scaffolds on the maturation and in vivo enrichment of DCs. We employ a precision templating method to make 3-D porous polymer scaffolds with uniformly defined and adjustable architecture. Hydrophilic pHEMA and hydrophobic PDMS scaffolds were fabricated in three pore sizes (20, 40, 90??m) to quantify scaffold pore size effects on DCs activation/maturation in vitro and in vivo. In vitro results showed that both pHEMA and PDMS scaffolds could promote maturation in the DC cell line, JAWSII, that resembled lipopolysaccharide (LPS)-activated/matured DCs (mDCs). Scaffolds with smaller pore sizes correlate with higher DC maturation, regardless of the polymer used. In vivo, when implanted subcutaneously in C57BL/6J mice, scaffolds with smaller pore sizes also demonstrated more DCs recruitment and more sustained activation. Without the use of DC chemo-attractants or chemical adjuvants, our results suggested that DC maturation and scaffold infiltration profile can be modulated by simply altering the pore size of the scaffolds.

SUBMITTER: Chen R

PROVIDER: S-EPMC6176859 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Precision-porous templated scaffolds of varying pore size drive dendritic cell activation.

Chen Ruying R Ma Hongyan H Zhang Lei L Bryers James D JD

Biotechnology and bioengineering 20180122 4

Scaffold based systems have shown significant potential in modulating immune responses in vivo. While there has been much attention on macrophage interactions with tissue engineered scaffolds for tissue regeneration, fewer studies have looked at the effects of scaffold design on the response of immune cells-that is, dendritic cells (DCs). Here, we present the effects of varying pore size of poly (2-hydroxyethyl methacrylate) (pHEMA) and poly(dimethylsiloxane) (PDMS, silicone) scaffolds on the ma ...[more]

PMID: 29280498

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Project description:3D printed scaffolds can be used, for example, in medical applications for simulating body tissues or for manufacturing prostheses. However, it is difficult to print porous structures of specific porosity and pore size values with fused deposition modelling (FDM) technology. The present paper provides a methodology to design porous structures to be printed. First, a model is defined with some theoretical parallel planes, which are bounded within a geometrical figure, for example a disk. Each plane has randomly distributed points on it. Then, the points are joined with lines. Finally, the lines are given a certain volume and the structure is obtained. The porosity of the structure depends on three geometrical variables: the distance between parallel layers, the number of columns on each layer and the radius of the columns. In order to obtain mathematical models to relate the variables with three responses, the porosity, the mean of pore diameter and the variance of pore diameter of the structures, design of experiments with three-level factorial analysis was used. Finally, multiobjective optimization was carried out by means of the desirability function method. In order to favour fixation of the structures by osseointegration, porosity range between 0.5 and 0.75, mean of pore size between 0.1 and 0.3 mm, and variance of pore size between 0.000 and 0.010 mm² were selected. Results showed that the optimal solution consists of a structure with a height between layers of 0.72 mm, 3.65 points per mm² and a radius of 0.15 mm. It was observed that, given fixed height and radius values, the three responses decrease with the number of points per surface unit. The increase of the radius of the columns implies the decrease of the porosity and of the mean of pore size. The decrease of the height between layers leads to a sharper decrease of both the porosity and the mean of pore size. In order to compare calculated and experimental values, scaffolds were printed in polylactic acid (PLA) with FDM technology. Porosity and pore size were measured with X-ray tomography. Average value of measured porosity was 0.594, while calculated porosity was 0.537. Average value of measured mean of pore size was 0.372 mm, while calculated value was 0.434 mm. Average value of variance of pore size was 0.048 mm², higher than the calculated one of 0.008 mm². In addition, both round and elongated pores were observed in the printed structures. The current methodology allows designing structures with different requirements for porosity and pore size. In addition, it can be applied to other responses. It will be very useful in medical applications such as the simulation of body tissues or the manufacture of prostheses.

Dataset Information

Precision-porous templated scaffolds of varying pore size drive dendritic cell activation.

Publications

Precision-porous templated scaffolds of varying pore size drive dendritic cell activation.

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