Lyophilized Scaffolds Fabricated from 3D-Printed Photocurable Natural Hydrogel for Cartilage Regeneration
Lyophilized Scaffolds Fabricated from 3D-Printed Photocurable Natural Hydrogel for Cartilage Regeneration
复制标题
由 3D 打印光固化天然水凝胶制成的冻干支架用于软骨再生
DOI：
10.1021/acsami.8b10926
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发表时间：
2018-09-19
影响因子：
9.5
通讯作者：
Zhou, Guangdong
中科院分区：
文献类型：
--
作者：
Xia, Huitang;Zhao, Dandan;Zhou, Guangdong
软骨缺损的修复在临床治疗中极具挑战性。组织工程为软骨的再生和修复提供了一条新的途径。作为组织工程的核心组成部分，支架材料对软骨再生有着至关重要的影响，尤其是在免疫功能正常的大型动物和人体中。天然聚合物，如明胶和透明质酸，是理想的仿生软骨再生支架来源。然而，如何精确控制它们的结构、降解速率和适合软骨再生的机械性能仍然是一个巨大的挑战。为了解决这些问题，在本研究中引入了一系列策略来优化支架制造。首先，将明胶和透明质酸制备成水凝胶，并采用3D打印来确保外部3D形状和内部孔结构的精确控制。其次，将甲基丙烯酸酐和光引发剂引入水凝胶系统中，使材料在3D打印过程中可光固化。最后，冻干用于进一步增强机械性能和延长降解时间。根据目前的结果，通过整合光固化3D打印和冻干技术，明胶和透明质酸成功地制造成了人耳和鼻形支架，与原始数字模型相比，两种支架的形状相似度均达到90%以上。具有50%填充密度的支架实现了适合于细胞分布、粘附和增殖的适当的内部孔结构。此外，冻干进一步增强了3D打印水凝胶的机械强度，并减缓了其与软骨再生相匹配的降解速率。最重要的是，与软骨细胞结合的支架在体外和自体山羊模型中成功地再生了具有典型陷窝结构和软骨特异性细胞外基质的成熟软骨。本研究建立了天然聚合物的新型支架制造策略，并提供了一种新型天然3D支架，其具有令人满意的外形、孔结构、机械强度、降解速率和用于软骨再生的弱免疫原性。
Repair of cartilage defects is highly challenging in clinical treatment. Tissue engineering provides a promising approach for cartilage regeneration and repair. As a core component of tissue engineering, scaffolds have a crucial influence on cartilage regeneration, especially in immunocompetent large animal and human. Native polymers, such as gelatin and hyaluronic acid, have known as ideal biomimetic scaffold sources for cartilage regeneration. However, how to precisely control their structure, degradation rate, and mechanical properties suitable for cartilage regeneration remains a great challenge. To address these issues, a series of strategies were introduced in the current study to optimize the scaffold fabrication. First, gelatin and hyaluronic acid were prepared into a hydrogel and 3D printing was adopted to ensure precise control in both the outer 3D shape and internal pore structure. Second, methacrylic anhydride and a photoinitiator were introduced into the hydrogel system to make the material photocurable during 3D printing. Finally, lyophilization was used to further enhance mechanical properties and prolong degradation time. According to the current results, by integrating photocuring 3D printing and lyophilization techniques, gelatin and hyaluronic acid were successfully fabricated into human ear- and nose-shaped scaffolds, and both scaffolds achieved shape similarity levels over 90% compared with the original digital models. The scaffolds with 50% infill density achieved proper internal pore structure suitable for cell distribution, adhesion, and proliferation. Besides, lyophilization further enhanced mechanical strength of the 3D-printed hydrogel and slowed its degradation rate matching to cartilage regeneration. Most importantly, the scaffolds combined with chondrocytes successfully regenerated mature cartilage with typical lacunae structure and cartilage-specific extracellular matrixes both in vitro and in the autologous goat model. The current study established novel scaffold-fabricated strategies for native polymers and provided a novel natural 3D scaffold with satisfactory outer shape, pore structure, mechanical strength, degradation rate, and weak immunogenicity for cartilage regeneration.