Gao Xiang, Song Jinlin, Zhang Yancong, Xu Xiao, Zhang Siqi, Ji Ping, Wei Shicheng
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education , Chongqing 401147, China.
Department of Oral and Maxillofacial Surgery, Central Laboratory, Peking University School and Hospital of Stomatology , Beijing 100081, China.
ACS Appl Mater Interfaces. 2016 Oct 19;8(41):27594-27610. doi: 10.1021/acsami.6b10417. Epub 2016 Oct 7.
The design and development of functional biomimetic systems for programmed stem cell response is a field of topical interest. To mimic bone extracellular matrix, we present an innovative strategy for constructing drug-loaded composite nanofibrous scaffolds in this study, which could integrate multiple cues from calcium phosphate mineral, bioactive molecule, and highly ordered fiber topography for the control of stem cell fate. Briefly, inspired by mussel adhesion mechanism, a polydopamine (pDA)-templated nanohydroxyapatite (tHA) was synthesized and then surface-functionalized with bone morphogenetic protein-7-derived peptides via catechol chemistry. Afterward, the resulting peptide-loaded tHA (tHA/pep) particles were blended with polycaprolactone (PCL) solution to fabricate electrospun hybrid nanofibers with random and aligned orientation. Our research demonstrated that the bioactivity of grafted peptides was retained in composite nanofibers. Compared to controls, PCL-tHA/pep composite nanofibers showed improved cytocompatibility. Moreover, the incorporated tHA/pep particles in nanofibers could further facilitate osteogenic differentiation potential of human mesenchymal stem cells (hMSCs). More importantly, the aligned PCL-tHA/pep composite nanofibers showed more osteogenic activity than did randomly oriented counterparts, even under nonosteoinductive conditions, indicating excellent performance of biomimetic design in cell fate decision. After in vivo implantation, the PCL-tHA/pep composite nanofibers with highly ordered structure could significantly promote the regeneration of lamellar-like bones in a rat calvarial critical-sized defect. Accordingly, the presented strategy in our work could be applied for a wide range of potential applications in not only bone regeneration application but also pharmaceutical science.
用于编程干细胞反应的功能性仿生系统的设计与开发是一个备受关注的热门领域。为了模拟骨细胞外基质，我们在本研究中提出了一种构建载药复合纳米纤维支架的创新策略，该策略可以整合来自磷酸钙矿物质、生物活性分子和高度有序纤维拓扑结构的多种线索，以控制干细胞命运。简而言之，受贻贝粘附机制的启发，合成了一种聚多巴胺（pDA）模板化的纳米羟基磷灰石（tHA），然后通过儿茶酚化学用骨形态发生蛋白-7衍生肽进行表面功能化。之后，将所得的载肽tHA（tHA/pep）颗粒与聚己内酯（PCL）溶液混合，以制备具有随机和排列取向的电纺混合纳米纤维。我们的研究表明，接枝肽的生物活性保留在复合纳米纤维中。与对照相比，PCL-tHA/pep复合纳米纤维表现出更好的细胞相容性。此外，纳米纤维中掺入的tHA/pep颗粒可以进一步促进人间充质干细胞（hMSCs）的成骨分化潜能。更重要的是，即使在非骨诱导条件下，排列的PCL-tHA/pep复合纳米纤维也比随机取向的对应物表现出更强的成骨活性，这表明仿生设计在细胞命运决定方面具有优异的性能。体内植入后，具有高度有序结构的PCL-tHA/pep复合纳米纤维可以显著促进大鼠颅骨临界尺寸缺损处层状骨的再生。因此，我们工作中提出的策略不仅可应用于骨再生领域，还可应用于药学领域的广泛潜在应用。
