In an effort to contribute to research in scalable production systems for polymeric delivery systems loaded with antimicrobial peptides (AMPs), we here investigate effects of hydrodynamic flow conditions on microfluidic particle generation. For this purpose, rapid prototyping using 3D printing was applied to prepare micromixers with three different geometric designs, which were used to prepare Ca²⁺-cross-linked alginate microgels loaded with the AMP polymyxin B in a continuous process. Based on fluid dynamic simulations, the hydrodynamic flow patterns in the micromixers were designed to be either (i) turbulent with chaotic disruption, (ii) laminar with convective mixing, or (iii) convective with microvortex formation. The physicochemical properties of the microgels prepared with these micromixers were characterized by photon correlation spectroscopy, laser-Doppler micro-electrophoresis, small-angle x-ray scattering, and ellipsometry. The particle size and compactness were found to depend on the micromixer geometry: From such studies, particle size and compactness were found to depend on micromixer geometry, the smallest and most compact particles were obtained by preparation involving microvortex flows, while larger and more diffuse microgels were formed upon laminar mixing. Polymyxin B was found to be localized in the particle interior and to cause particle growth with increasing peptide loading. Ca²⁺-induced cross-linking of alginate, in turn, results in particle contraction. The peptide encapsulation efficiency was found to be higher than 80% for all investigated micromixer designs; the highest encapsulation efficiency observed for the smallest particles generated by microvortex-mediated self-assembly. Ellipsometry results for surface-immobilized microgels, as well as results on peptide encapsulation, demonstrated electrolyte-induced peptide release. Taken together, these findings demonstrate that rapid prototyping of microfluidics using 3D-printed micromixers offers promises for continuous manufacturing of AMP-loaded microgels. Although the micromixer combining turbulent flow and microvortexes was demonstrated to be the most efficient, all three micromixer designs were found to mediate self-assembly of small microgels displaying efficient peptide encapsulation. This demonstrates the robustness of employing 3D-printed micromixers for microfluidic assembly of AMP-loaded microgels during continuous production.

为了为可扩展生产系统的研究做出贡献，该系统用于载有抗菌肽（AMP）的聚合物输送系统，我们在这里研究流体动力学流动条件对微流体颗粒产生的影响。为了这个目的，使用3D打印的快速原型被应用于制备具有三种不同几何设计的微混合器，所述微混合器被用于以连续过程制备负载有AMP多粘菌素B的Ca 2 ⁺ -交联的藻酸盐微凝胶。基于流体动力学模拟，将微型混合器中的流体动力学流型设计为（i）带有紊乱的湍流，（ii）对流混合的层流或（iii）与微涡旋形成对流。用光子相关光谱，激光多普勒微电泳，小角X射线散射和椭圆偏振法对用这些微混合器制备的微凝胶的理化性质进行了表征。发现颗粒大小和密实度取决于微混合器的几何形状：从此类研究中，发现颗粒大小和密实度取决于微混合器的几何形状，通过涉及微涡流的制备获得最小和最紧密的颗粒，而较大和更多分散的微凝胶在层流混合时形成。发现多粘菌素B位于颗粒内部，并随着肽负载的增加而引起颗粒生长。钙²⁺诱导的藻酸盐的交联又导致颗粒收缩。对于所有研究的微混合器设计，发现肽的包封效率均高于80％。对于微涡旋介导的自组装产生的最小颗粒，观察到的最高包封效率。表面固定的微凝胶的椭偏结果以及肽包封的结果证明了电解质诱导的肽释放。综上所述，这些发现表明，使用3D打印的微混合器对微流体进行快速原型设计可为连续制造AMP装载的微凝胶提供希望。尽管已证明结合湍流和微涡流的微型混合器是最有效的，发现所有这三种微混合器设计都可以介导小微凝胶的自组装，从而显示出有效的肽包封。这证明了在连续生产过程中，使用3D打印的微混合器对装有AMP的微凝胶进行微流体组装的鲁棒性。