3D bioprinting via an in situ crosslinking technique towards engineering cartilage tissue
3D bioprinting via an in situ crosslinking technique towards engineering cartilage tissue
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DOI：
10.1038/s41598-019-56117-3
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发表时间：
2019-12-27
影响因子：
4.6
通讯作者：
Burdick, Jason A.
中科院分区：
文献类型：
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作者：
Galarraga, Jonathan H.;Kwon, Mi Y.;Burdick, Jason A.
3D生物打印是一种有前途的方法，用于修复因损伤或疾病造成的损伤后的软骨组织;然而，3D打印支架的设计受到具有必要的可打印性，细胞相容性和生物活性的生物墨水的可用性的限制。为了解决这个问题，我们开发了一种称为原位交联的方法，该方法允许在沉积之前通过光可渗透的毛细管通过光直接固化生物墨水来打印非粘性的、可光交联的生物墨水。使用二烯改性的透明质酸（NorHA）大分子单体作为代表性的生物墨水和我们对可见光下硫醇-烯固化动力学的理解，我们改变了打印参数（例如，毛细管长度、流速、光强度）来识别对于油墨最佳的印刷条件。打印过程是细胞相容性的，在整个打印的构建体中观察到高细胞活力和间充质基质细胞（MSC）的均匀分布。在软骨形成培养基中培养超过56天，打印的构建体的压缩模量、生化含量（即，硫酸化糖胺聚糖、胶原蛋白）和与软骨组织相关的基质的组织学染色。这种可推广的打印方法可以用于修复关节软骨中的局灶性缺陷，或者广泛地用于现在可以打印的一系列可光交联生物墨水的广泛生物医学应用。
3D bioprinting is a promising approach for the repair of cartilage tissue after damage due to injury or disease; however, the design of 3D printed scaffolds has been limited by the availability of bioinks with requisite printability, cytocompatibility, and bioactivity. To address this, we developed an approach termed in situ crosslinking that permits the printing of non-viscous, photocrosslinkable bioinks via the direct-curing of the bioink with light through a photopermeable capillary prior to deposition. Using a norbornene-modified hyaluronic acid (NorHA) macromer as a representative bioink and our understanding of thiol-ene curing kinetics with visible light, we varied the printing parameters (e.g., capillary length, flow rate, light intensity) to identify printing conditions that were optimal for the ink. The printing process was cytocompatible, with high cell viability and homogenous distribution of mesenchymal stromal cells (MSCs) observed throughout printed constructs. Over 56 days of culture in chondrogenic media, printed constructs increased in compressive moduli, biochemical content (i.e., sulfated glycosaminoglycans, collagen), and histological staining of matrix associated with cartilage tissue. This generalizable printing approach may be used towards the repair of focal defects in articular cartilage or broadly towards widespread biomedical applications across a range of photocrosslinkable bioinks that can now be printed.