Bioprinted Constructs that Mimic the Ossification Center Microenvironment for Targeted Innervation in Bone Regeneration
Bioprinted Constructs that Mimic the Ossification Center Microenvironment for Targeted Innervation in Bone Regeneration
复制标题
模拟骨化中心微环境的生物打印结构，用于骨再生的定向神经支配
DOI：
10.1002/adfm.202109871
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发表时间：
2021-11-23
影响因子：
19
通讯作者：
Wang, Jinwu
中科院分区：
文献类型：
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作者：
Li, Wentao;Miao, Weiqiang;Wang, Jinwu
尽管工程化骨组织已经取得了很大的进展，但由于在其设计中缺乏神经网络重建，延迟或无效的骨再生仍然是一个问题。因此，提出了一种模拟骨化中心微环境以促进神经支配的工程化骨组织构建体。基于此，通过生物打印技术构建了NGF@Lap构建体，该构建体能够长时间释放神经生长因子（NGF），并以高表达的NGF模拟骨化中心的微环境。在体外，NGF@Lap‐GA可以促进轴突延伸。同时，构建体中的NGF和Laponite可分别促进感觉神经元中降钙素基因相关肽（CGRP）的表达和分泌。此外，构建体显示CGRP依赖性成骨和脂肪生成抑制，其主要由AMP活化蛋白激酶-过氧化物酶体增殖物活化受体途径调节。在体内，该结构增加了植入物周围组织中的神经血管网络密度，促进了骨髓间充质干细胞的成骨分化，并有效地改善了颅骨缺损模型中的骨再生。总之，新型组织工程骨模拟骨化中心微环境，促进神经支配，在未来的骨再生应用中具有广阔的潜力。
Although great progress has been made in engineered bone tissues, delayed or ineffective bone regeneration remains an issue due to the lack of neural network reconstruction in their design. Therefore, an engineered bone tissue construct that mimics the ossification center microenvironment to promote innervation is proposed. Based on this, the NGF@Lap constructs are constructed through bioprinting technology, which can release nerve growth factor (NGF) for a long time and simulate the ossification center's microenvironment with high expression NGF. In vitro, NGF@Lap‐GA can promote axonal extension. Meanwhile, the NGF and Laponite from the constructs can respectively promote the expression and secretion of calcitonin gene‐related peptide (CGRP) in sensory neurons. Further, the constructs show a CGRP‐dependent osteogenic and inhibition of adipogenesis, which is mainly regulated by AMP‐activated protein kinase‐peroxisome proliferator activated receptor pathway. In vivo, the constructs increased neurovascular network density in the tissue surrounding the implant, promoted bone marrow mesenchymal stem cells osteogenic differentiation, and effectively improved bone regeneration in the cranial defect model. In conclusion, the novel tissue‐engineered bone simulates the ossification center microenvironment, promotes innervation, and has promising potential for future application in bone regeneration.