Trinity Centre for Bioengineering and Department of Mechanical and Manufacturing Engineering, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
Departments of Biomedical Engineering and Orthopedic Surgery, and the National Centre for Regenerative Medicine, Case Western Reserve University, Cleveland, OH, USA.
Adv Healthc Mater. 2016 Sep;5(18):2353-62. doi: 10.1002/adhm.201600182. Epub 2016 Jun 9.
The ability to print defined patterns of cells and extracellular-matrix components in three dimensions has enabled the engineering of simple biological tissues; however, bioprinting functional solid organs is beyond the capabilities of current biofabrication technologies. An alternative approach would be to bioprint the developmental precursor to an adult organ, using this engineered rudiment as a template for subsequent organogenesis in vivo. This study demonstrates that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp adhesion peptides. Furthermore, these soft tissue templates can be reinforced with a network of printed polycaprolactone fibers, resulting in a ≈350 fold increase in construct compressive modulus providing the necessary stiffness to implant such immature cartilaginous rudiments into load bearing locations. As a proof-of-principal, multiple-tool biofabrication is used to engineer a mechanically reinforced cartilaginous template mimicking the geometry of a vertebral body, which in vivo supported the development of a vascularized bone organ containing trabecular-like endochondral bone with a supporting marrow structure. Such developmental engineering approaches could be applied to the biofabrication of other solid organs by bioprinting precursors that have the capacity to mature into their adult counterparts over time in vivo.
能够在三维空间中打印定义的细胞和细胞外基质成分模式，使简单的生物组织工程成为可能；然而，生物打印功能性实体器官超出了当前生物制造技术的能力。一种替代方法是生物打印成年器官的发育前体，使用这种工程化的雏形作为体内随后器官发生的模板。本研究表明，可以使用含有 Arg-Gly-Asp 粘附肽的支持性伽马辐照藻酸盐生物墨水内的干细胞在体外工程化发育诱导性肥大软骨模板。此外，可以用打印的聚己内酯纤维网络来增强这些软组织模板，从而使构建体的压缩模量增加约 350 倍，为植入这种未成熟的软骨雏形提供必要的刚度，使其能够植入承重部位。作为原理验证，多工具生物制造用于工程化模仿椎体几何形状的机械增强软骨模板，该模板在体内支持了包含小梁样软骨内骨和支持骨髓结构的血管化骨器官的发育。通过生物打印具有随时间在体内成熟为其成体对应物的能力的前体，可以将这种发育工程方法应用于其他实体器官的生物制造。
