3D printing viscoelastic hydrogel-based scaffolds with a swelling-dependent gate for cartilage injury regeneration
3D printing viscoelastic hydrogel-based scaffolds with a swelling-dependent gate for cartilage injury regeneration
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DOI：
10.1016/j.cej.2023.147260
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发表时间：
2023-11
影响因子：
15.1
通讯作者：
Anan Zhang;Lili Sun;Kai Chen;Changsheng Liu;Yuan Yuan-Yuan
中科院分区：
文献类型：
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作者：
Anan Zhang;Lili Sun;Kai Chen;Changsheng Liu;Yuan Yuan-Yuan
由于自愈能力差、稳定性差，关节软骨的再生仍然是一个巨大的挑战。微骨折手术（MF）可以提供骨髓间充质干细胞（BMSCs），在临床上普遍使用，但由于缺乏有效的粘附基质以及无法控制的纤维化甚至矿化倾向，其治疗效果仍然受到限制。在这项研究中，成功开发了一种基于小分子载药粘弹性水凝胶的3D打印双层支架，具有膨胀依赖性门，以解决这些局限性。该支架由孔径较小的下层和孔径较大的上层基质组成。前者作为肿胀依赖性门来改变孔径，最初处于开启状态，允许骨髓间充质干细胞浸润，并最终转变为关闭状态，在肿胀引起的毛孔闭合后，充当屏障，阻止骨髓过度血液支持。这种屏障结构与脂肪酸抑制剂一起抑制新软骨基质的肥大。后者提供了生物相容性和粘弹性基质，以引导 MSC 实现稳定的软骨形成。通过将结构设计与抑制剂相结合，双层支架为未来 MF 手术在软骨再生中的临床应用提供了一个有前途的平台。
Regeneration of articular cartilage remains a great challenge due to its poor self-healing capacity and weak stability. The microfracture surgery (MF) can provide bone marrow mesenchymal stem cells (BMSCs) and is commonly used in clinical practice, but its therapeutic effect is still limited by the lack of effective adhesion matrix and the uncontrollable tendency to develop fibrosis and even mineralization. In this study, a small molecular drug-loaded viscoelastic hydrogel-based 3D printing bilayer scaffold with a swelling-dependent gate was successfully developed to address these limitations. The scaffold consisted of a lower layer with a smaller pore size and an upper matrix with larger pore size. The former acted as a swelling-dependent gate to switch pore size, which initially was on-state allowing the infiltration of BMSCs, and eventually transformed into off-state serving as a barrier blocking excessive blood support from the bone marrow after swelling-induced closure of pores. This barrier structure cooperated with fatty acid inhibitor-suppressed hypertrophy of neo-cartilage matrix. The latter provided a biocompatible and viscoelastic matrix to guide MSCs toward stable chondrogenic commitment. By integrating structural design with the inhibitor, the bilayer scaffold provides a promising platform for future clinical applications of MF surgery in cartilage regeneration.