Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
Biomater Adv. 2023 Oct;153:213539. doi: 10.1016/j.bioadv.2023.213539. Epub 2023 Jun 30.
Pre-formed hydrogel scaffolds have emerged as favorable vehicles for tissue regeneration, promoting minimally invasive treatment of native tissue. However, due to the high degree of swelling and inherently poor mechanical properties, development of complex structural hydrogel scaffolds at different dimensional scales has been a continuous challenge. Herein, we take a novel approach at the intersections of engineering design and bio-ink chemistry to develop injectable pre-formed structural hydrogel scaffolds fabricated via visible light (VL) induced digital light processing (DLP). In this study, we first determined the minimum concentration of poly(ethylene glycol) diacrylate (PEGDA) to be added to the gelatin methacrylate (GelMA) bio-ink in order to achieve scalable and high printing-fidelity with desired cell adhesion, viability, spreading, and osteogenic differentiation characteristics. Despite the advantages of hybrid GelMA-PEGDA bio-ink in improving scalability and printing-fidelity, compressibility, shape-recovery, and injectability of the 3D bioprinted scaffolds were compromised. To restore these needed characteristics for minimally invasive tissue regeneration applications, we performed topological optimization to design highly compressible and injectable pre-formed (i.e., 3D bioprinted) microarchitectural scaffolds. The designed injectable pre-formed microarchitectural scaffolds showed a great capacity to retain the viability of the encapsulated cells (>72 % after 10 cycles of injection). Lastly, ex ovo chicken chorioallantoic membrane (CAM) studies revealed that the optimized injectable pre-formed hybrid hydrogel scaffold is biocompatible and supports angiogenic growth.
预先形成的水凝胶支架已成为组织再生的有利载体，可促进对原生组织的微创治疗。然而，由于高度的溶胀和固有的机械性能差，在不同的维度尺度上开发复杂结构的水凝胶支架一直是一个持续的挑战。在此，我们在工程设计和生物墨水化学的交叉点上采取了一种新方法，通过可见光 (VL) 诱导的数字光处理 (DLP) 开发可注射的预先形成的结构水凝胶支架。在这项研究中，我们首先确定了聚乙二醇二丙烯酸酯 (PEGDA) 添加到明胶甲基丙烯酸酯 (GelMA) 生物墨水中的最小浓度，以实现具有所需细胞粘附、活力、扩展和成骨分化特性的可扩展和高打印保真度。尽管混合 GelMA-PEGDA 生物墨水在提高可扩展性和打印保真度方面具有优势，但 3D 生物打印支架的可压缩性、形状恢复性和可注射性受到了影响。为了恢复这些用于微创组织再生应用的必要特性，我们进行了拓扑优化设计，以设计高度可压缩和可注射的预先形成（即 3D 生物打印）微结构支架。设计的可注射预先形成的微结构支架表现出保持封装细胞活力的巨大能力（注射 10 次后仍保持>72%的活力）。最后，鸡胚绒毛尿囊膜（CAM）研究表明，优化的可注射预先形成的混合水凝胶支架具有生物相容性，并支持血管生成生长。
