IEEE Trans Nanobioscience. 2019 Apr;18(2):261-264. doi: 10.1109/TNB.2019.2905510. Epub 2019 Mar 15.
Controlled cell delivery has shown some promising outcomes compared with traditional cell delivery approaches over the past decades, and strategies focused on optimization or engineering of controlled cell delivery have been intensively studied. In this paper, we demonstrate the fabrication of a 3D printed hydrogel scaffold infused with degradable PEGPLA/NB composite hydrogel core for controlled cell delivery with improved cell viability and facile tunability. The 3D printed poly (ethylene glycol) diacrylate (PEGDA) scaffold with specifically designed architectures can provide mechanical support while allowing bidirectional diffusion of small molecules, thus permitting structural integrity and long-term cell viability. Poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA), which is highly susceptible to hydrolysis, however, the acrylation reactions it utilizes for chain growth have been reported as toxic to cells. Poly(ethylene glycol) norbornene (PEGNB), validated for its excellent cytocompatibility, was therefore mixed and infused together with PLA-PEG-PLA into the printed PEGDA scaffold. Cells encapsulated microfluidically into PEGNB microspheres and then polymerized within PEGPLA/NB composite hydrogel maintained excellent viability over a week. Controlled cell release was achieved via the manipulation of PEGPLA/NB composition. By increasing PEGNB proportion in the core, cell release was significantly slowed while increasing PLA-PEG-PLA proportion eventually resulted in a very robust cell release within a short time frame. The functionality of released cells was validated by their cell viability and proliferation potential. In summary, we have shown this droplet-microencapsulation technique coupled with composite degradable hydrogel and 3D printing could offer an alternative route for controlled cell delivery.
在过去几十年中，与传统的细胞递送方法相比，受控细胞递送显示出了一些有前景的结果，并且集中于优化或工程化受控细胞递送的策略已经得到了深入研究。在本文中，我们展示了一种 3D 打印水凝胶支架的制造，该支架中注入了可降解的 PEGPLA/NB 复合水凝胶芯，用于控制细胞递送，提高了细胞活力和易于调节性。具有特定设计结构的 3D 打印聚乙二醇二丙烯酸酯（PEGDA）支架可以提供机械支撑，同时允许小分子的双向扩散，从而保持结构完整性和长期细胞活力。然而，聚乳酸-聚乙二醇-聚乳酸（PLA-PEG-PLA）高度易水解，但其用于链增长的丙烯酰化反应已被报道对细胞有毒。因此，聚乙二醇降冰片烯（PEGNB）被混合并注入到打印的 PEGDA 支架中。细胞被微流控封装到 PEGNB 微球中，然后在 PEGPLA/NB 复合水凝胶中聚合，在一周内保持良好的活力。通过操纵 PEGPLA/NB 组成，可以实现受控的细胞释放。通过增加核心中的 PEGNB 比例，可以显著减缓细胞释放速度，而增加 PLA-PEG-PLA 比例最终会在短时间内导致非常强劲的细胞释放。通过细胞活力和增殖潜力验证了释放细胞的功能。总之，我们已经表明，这种液滴微包封技术与复合可降解水凝胶和 3D 打印相结合，可以为受控细胞递送提供另一种途径。
