Medical Devices, Life Sciences Division, National Research Council of Canada, Boucherville, QC J4B 6Y4, Canada.
Center for Research and Applications in Fluidic Technologies (CRAFT), Toronto, ON M5S 3G8, Canada.
Lab Chip. 2024 Oct 22;24(21):4948-4961. doi: 10.1039/d4lc00530a.
Transplantable ready-made microvessels have therapeutic potential for tissue regeneration and cell replacement therapy. Inspired by the natural rapid angiogenic sprouting of microvessels , engineered injectable 3D microvessel networks are created using thermoplastic elastomer (TPE) microfluidic devices. The TPE material used here is flexible, optically transparent, and can be robustly yet reversibly bonded to a variety of plastic substrates, making it a versatile choice for microfluidic device fabrication because it overcomes the weak self-adhesion properties and limited manufacturing options of poly(dimethylsiloxane) (PDMS). By leveraging the reversible bonding characteristics of TPE material templates, we present their utility as an organ-on-a-chip platform for forming and handling microvessel networks, and demonstrate their potential for animal-free tissue generation and transplantation in clinical applications. We first show that TPE-based devices have nearly 6-fold higher bonding strength during the cell culture step compared to PDMS-based devices while simultaneously maintaining a full reversible bond to (PS) culture plates, which are widely used for biological cell studies. We also demonstrate the successful generation of perfusable and interconnected 3D microvessel networks using TPE-PS microfluidic devices on both single and multi-vessel loading platforms. Importantly, after removing the TPE slab, microvessel networks remain intact on the PS substrate without any structural damage and can be effectively harvested following gel digestion. The TPE-based organ-on-a-chip platform offers substantial advantages by facilitating the harvesting procedure and maintaining the integrity of microfluidic-engineered microvessels for transplant. To the best of our knowledge, our TPE-based reversible bonding approach marks the first confirmation of successful retrieval of organ-specific vessel segments from the reversibly-bonded TPE microfluidic platform. We anticipate that the method will find applications in organ-on-a-chip and microphysiological system research, particularly in tissue analysis and vessel engraftment, where flexible and reversible bonding can be utilized.
可移植的现成微血管具有组织再生和细胞替代治疗的治疗潜力。受微血管快速血管生成发芽的启发，使用热塑性弹性体 (TPE) 微流控装置创建了工程可注射 3D 微血管网络。这里使用的 TPE 材料具有柔韧性、光学透明性，并且可以与各种塑料基板牢固但可重复地结合，使其成为微流控器件制造的多功能选择，因为它克服了聚二甲基硅氧烷 (PDMS) 的弱自粘特性和有限的制造选择。通过利用 TPE 材料模板的可逆键合特性，我们展示了它们作为用于形成和处理微血管网络的芯片上器官平台的实用性，并展示了它们在无动物组织生成和移植方面的潜在应用在临床应用中。我们首先表明，与基于 PDMS 的设备相比，基于 TPE 的设备在细胞培养步骤中的结合强度高近 6 倍，同时与广泛用于生物细胞研究的 PS 培养板保持完全可逆的键合。我们还展示了在单血管和多血管加载平台上使用 TPE-PS 微流控装置成功生成可灌注和互连的 3D 微血管网络。重要的是，在去除 TPE 平板后，微血管网络在 PS 基板上保持完整，没有任何结构损坏，并且可以在凝胶消化后有效地收获。基于 TPE 的芯片上器官平台具有很大的优势，它可以简化收获过程并保持微流控工程微血管的完整性以进行移植。据我们所知，我们基于 TPE 的可逆键合方法首次证实了从可重复键合的 TPE 微流控平台成功回收特定于器官的血管段。我们预计该方法将在芯片上器官和微生理系统研究中得到应用，特别是在组织分析和血管移植中，可以利用灵活和可逆的键合。
