Cryogenically 3D printed biomimetic scaffolds containing decellularized small intestinal submucosa and Sr2+/Fe3+ co-substituted hydroxyapatite for bone tissue engineering
Cryogenically 3D printed biomimetic scaffolds containing decellularized small intestinal submucosa and Sr2+/Fe3+ co-substituted hydroxyapatite for bone tissue engineering
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DOI：
10.1016/j.cej.2021.133459
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发表时间：
2021-11
影响因子：
15.1
通讯作者：
Liang Yang;Shengyang Jin;Lei Shi;Ismat Ullah;Keda Yu;Wancheng Zhang;Lin Bo;Xianglin Zhang
中科院分区：
文献类型：
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作者：
Liang Yang;Shengyang Jin;Lei Shi;Ismat Ullah;Keda Yu;Wancheng Zhang;Lin Bo;Xianglin Zhang
目前，先进的骨生物材料更倾向于能够模仿天然骨的结构/组成，并具有足够的生物多功能性，以按时间顺序指示骨再生事件。这类生物材料在骨组织工程中应用前景广阔。因此，采用挤压低温3D打印的方法，构建由脱细胞小肠粘膜下层基质（SIS-ECM）和Sr2+/Fe3+共取代羟基磷灰石（SrFeHA）组成的新型仿生支架。制备的SIS/SrFeHA支架具有良好的三维宏观/微孔结构，粗糙的微表面和提高的机械强度，同时具有明显的生物活性ECM成分和Sr2+/Fe3+的协同释放。这些有利的物理化学性质使SIS/SrFeHA复合材料能够诱导高度仿生的骨环境，从而操纵所需的免疫调节，同时增强血管生成、成骨和生物矿化。同样，体内颅骨缺损和皮下植入的结果也证实了SIS/SrFeHA在早期免疫反应、新生血管和体内骨再生方面的优越能力，这表明SIS和SrFeHA在加速骨愈合方面具有强大的联合作用。此外，通过RNA测序分析，进一步明确了在SIS/SrFeHA支架中，Amot+/YAP−/Hippo信号通路上调与血管生成增强有关的新发现。因此，本研究首次强调了SIS/SrFeHA支架在诱导骨愈合方面的巨大潜力，同时为更好地理解生物活性SrFeHA成分的潜在机制提供了新的发现，从而可能为未来的骨组织工程提供新的有希望的替代方案。
Currently, advanced bone biomaterials are preferred able to mimic the architecture/composition of natural bone and possess sufficient biological multifunctionality to chronologically dictate bone regeneration events. Such biomaterials are increasingly being researched and quite promising in bone tissue engineering. In this view, novel biomimetic scaffolds composed of decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+co-substituted hydroxyapatite (SrFeHA) were constructed via extrusion cryogenic 3D printing method. The produced SIS/SrFeHA scaffolds revealed desirable 3D interconnected macro/micro-porous structures, rough microsurfaces and improved mechanical strength, along with appreciable synergic releasing of bioactive ECM components and Sr2+/Fe3+. These favorable physico-chemical properties rendered composite SIS/SrFeHA inducing a highly biomimetic bony environment which manipulated desired immunoregulation coupled with enhanced angiogenesis, osteogenesis, and biomineralization. Consistently, in vivo cranial defects and subcutaneous implantation outcomes yet affirmed the superior ability of SIS/SrFeHA to well dictate early immune reaction, neovascularization, and in vivo bone regeneration, suggesting the potent combined actions of SIS and SrFeHA to accelerate bone healing. Moreover, as examined by RNA sequencing assay, a new finding of up-regulated Amot+/YAP−/Hippo signaling pathway responsible for the enhanced angiogenesis in SIS/SrFeHA scaffolds was further clarified. Consequently, for the first time, present research highlights the considerable potential of SIS/SrFeHA scaffolds for inducing bone healing and simultaneously afford a new finding for better understanding underlying mechanism of bioactive SrFeHA components, thus may generating a new promising alternative for future bone tissue engineering.