Bioactive Sr2+/Fe3+ co-substituted hydroxyapatite in cryogenically 3D printed porous scaffolds for bone tissue engineering
Bioactive Sr2+/Fe3+ co-substituted hydroxyapatite in cryogenically 3D printed porous scaffolds for bone tissue engineering
复制标题
用于骨组织工程的低温 3D 打印多孔支架中的生物活性 Sr2/Fe3 共取代羟基磷灰石
DOI：
10.1088/1758-5090/abcf8d
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发表时间：
2021
期刊：
影响因子：
9
通讯作者：
Guo Xiaodong
中科院分区：
文献类型：
--
作者：
Yang Liang;Ullah Ismat;Yu Keda;Zhang Wancheng;Zhou Jinge;Sun Tingfang;Shi Lei;Yao Sheng;Chen Kaifang;Zhang Xianglin;Guo Xiaodong
开发具有生物多功能的多掺杂生物陶瓷是骨组织工程研究的热点。在这个观点中，先前已经有意设计了具有固定在10摩尔%的梯度掺杂浓度的创新的Sr 2 +/Fe 3+共取代的纳米羟基磷灰石。在本文中，为了评估其用于骨愈合的治疗潜力，通过挤出低温3D打印技术随后冻干来制造新型梯度SrFeHA/PCL支架。所获得的支架具有所需的三维互连的多孔结构和粗糙的微表面，沿着具有生物活性的Sr 2 +/Fe 3+从SrFeHA组分中释放。这些有利的物理化学性质使得打印的支架在体外和体内都实现了有效的生物学应用，特别是适度的共取代的Sr7.5Fe2.5HA和Sr 5 Fe 5 HA基团表现出显著增强的生物活性，其不仅直接促进MC 3 T3成骨细胞和HUVEC的功能，而且有力地操纵有利的巨噬细胞活化以同时促进骨生成/血管生成。此外，在体内皮下植入和颅骨缺损修复的结果进一步证实了其上级的能力，支配免疫反应，植入物血管化和原位骨再生，主要依赖于释放的Sr 2 +/Fe 3+的协同作用。因此，本研究首次强调了Sr7.5Fe2.5HA和Sr 5 Fe 5 HA通过免疫调节与增强血管生成和成骨作用的耦合来改善骨再生过程的巨大潜力，因此可能为未来的骨组织工程提供新的有前途的替代方案。
Developing multi-doped bioceramics that possess biological multifunctionality is becoming increasingly attractive and promising for bone tissue engineering. In this view innovative Sr2+/Fe3+ co-substituted nano-hydroxyapatite with gradient doping concentrations fixed at 10 mol% has been deliberately designed previously. Herein, to evaluate their therapeutic potentials for bone healing, novel gradient SrFeHA/PCL scaffolds are fabricated by extrusion cryogenic 3D printing technology with subsequent lyophilization. The obtained scaffolds exhibit desired 3D interconnected porous structure and rough microsurface, along with appreciable release of bioactive Sr2+/Fe3+ from SrFeHA components. These favorable physicochemical properties render printed scaffolds realizing effective biological applications both in vitro and in vivo, particularly the moderate co-substituted Sr7.5Fe2.5HA and Sr5Fe5HA groups exhibit remarkably enhanced bioactivity that not only promotes the functions of MC3T3 osteoblasts and HUVECs directly, but also energetically manipulates favorable macrophages activation to concurrently facilitate osteogenesis/angiogenesis. Moreover, in vivo subcutaneous implantation and cranial defects repair outcomes further confirm their superior capacity to dictate immune reaction, implants vascularization and in situ bone regeneration, mainly dependent on the synergetic effects of released Sr2+/Fe3+. Accordingly, for the first time, present study highlights the great potential of Sr7.5Fe2.5HA and Sr5Fe5HA for ameliorating bone regeneration process by coupling of immunomodulation with enhanced angio- and osteogenesis and hence may provide a new promising alternative for future bone tissue engineering.