Department of Bioengineering, University of Washington, Seattle, WA.
Biotechnol Bioeng. 2018 Apr;115(4):1086-1095. doi: 10.1002/bit.26532. Epub 2018 Jan 22.
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 μm) 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.
支架基系统在调节体内免疫反应方面显示出了巨大的潜力。虽然人们对组织工程支架与巨噬细胞相互作用以促进组织再生进行了大量研究,但很少有研究关注支架设计对免疫细胞(即树突状细胞 (DC))反应的影响。在这里,我们研究了改变聚 (2-羟乙基甲基丙烯酸酯) (pHEMA) 和聚二甲基硅氧烷 (PDMS,硅胶) 支架孔径对 DC 成熟和体内富集的影响。我们采用精密模板法制造具有均匀定义和可调节结构的 3D 多孔聚合物支架。制备了亲水性 pHEMA 和疏水性 PDMS 支架,孔径分别为 20、40 和 90μm,以量化支架孔径对 DC 体外和体内激活/成熟的影响。体外结果表明,pHEMA 和 PDMS 支架均能促进 DC 细胞系 JAWSII 的成熟,其特征类似于脂多糖 (LPS) 激活/成熟的 DC(mDC)。无论使用哪种聚合物,孔径较小的支架与更高的 DC 成熟度相关。在体内,当植入 C57BL/6J 小鼠的皮下时,孔径较小的支架也显示出更多的 DC 募集和更持续的激活。在不使用 DC 趋化因子或化学佐剂的情况下,我们的结果表明,通过简单改变支架的孔径可以调节 DC 的成熟和支架的渗透特征。