Wang Haoyu, Zhou Xiaqing, Wang Juan, Zhang Xinping, Zhu Meifeng, Wang Hongjun
Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, 07030, United States.
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ, 07030, United States.
Bioact Mater. 2022 Jan 29;17:261-275. doi: 10.1016/j.bioactmat.2022.01.030. eCollection 2022 Nov.
One of the pivotal factors that limit the clinical translation of tissue engineering is the inability to create large volume and complex three-dimensional (3D) tissues, mainly due to the lack of long-range mass transport with many current scaffolds. Here we present a simple yet robust sacrificial strategy to create hierarchical and perfusable microchannel networks within versatile scaffolds via the combination of embedded 3D printing (EB3DP), tunable polyelectrolyte complexes (PEC), and casting methods. The sacrificial templates of PEC filaments (diameter from 120 to 500 μm) with arbitrary 3D configurations were fabricated by EB3DP and then incorporated into various castable matrices (e.g., hydrogels, organic solutions, meltable polymers, etc.). Rapid dissolution of PEC templates within a 2.00 M potassium bromide aqueous solution led to the high fidelity formation of interconnected channels for free mass exchange. The efficacy of such channeled scaffolds for in vitro tissue formation was demonstrated with mouse fibroblasts, showing continuous cell proliferation and ECM deposition. Subcutaneous implantation of channeled silk fibroin (SF) scaffolds with a porosity of 76% could lead to tissue ingrowth as high as 53% in contrast to 5% for those non-channeled controls after 4 weeks. Both histological and immunofluorescence analyses demonstrated that such channeled scaffolds promoted cellularization, vascularization, and host integration along with immunoregulation.
限制组织工程临床转化的关键因素之一是无法制造出大体积且复杂的三维（3D）组织，这主要是由于目前许多支架缺乏长距离的物质传输。在此，我们提出一种简单而稳健的牺牲策略，通过结合嵌入式3D打印（EB3DP）、可调聚电解质复合物（PEC）和浇铸方法，在多功能支架内创建分层且可灌注的微通道网络。通过EB3DP制造具有任意3D构型的PEC细丝（直径为120至500μm）的牺牲模板，然后将其纳入各种可浇铸基质（如水凝胶、有机溶液、可熔聚合物等）中。PEC模板在2.00 M溴化钾水溶液中快速溶解，导致形成用于自由物质交换的相互连接通道的高保真度。用小鼠成纤维细胞证明了这种带通道支架用于体外组织形成的功效，显示出细胞的持续增殖和细胞外基质沉积。孔隙率为76%的带通道丝素蛋白（SF）支架皮下植入4周后，组织向内生长高达53%，相比之下，非通道对照仅为5%。组织学和免疫荧光分析均表明，这种带通道支架促进了细胞化、血管化和宿主整合以及免疫调节。
