Steroid-associated osteonecrosis (SAON) often requires surgical core decompression (CD) in the early stage for removal of necrotic bone to facilitate repair where bone grafts are needed for filling bone defect and avoiding subsequent joint collapse. In this study, we developed a bioactive composite scaffold incorporated with icariin, a unique phytomolecule that can provide structural and mechanical support and facilitate bone regeneration to fill into bone defects after surgical CD in established SAON rabbit model. An innovative low-temperature 3D printing technology was used to fabricate the poly (lactic-co-glycolic acid)/β-calcium phosphate/icariin (PLGA/TCP/Icariin, PTI) scaffold. The cytocompatibility of the PTI scaffold was tested in vitro, and the osteogenesis properties of PTI scaffolds were assessed in vivo in the SAON rabbit models. Our results showed that the fabricated PTI scaffold had a well-designed biomimic structure that was precisely printed to provide increased mechanical support and stable icariin release from the scaffold for bone regeneration. Furthermore, our in vivo study indicated that the PTI scaffold could enhanced the mechanical properties of new bone tissues and improved angiogenesis within the implanted region in SAON rabbit model than those of PLGA/TCP (PT) scaffold. The underlying osteoblastic mechanism was investigated using MC3T3-E1 cells in vitro and revealed that icariin could facilitate MC3T3-E1 cells ingrowth into the PTI scaffold and regulate osteoblastic differentiation. The PTI scaffold exhibited superior biodegradability, biocompatibility, and osteogenic capability compared with those of PT scaffold. In summary, the PTI composite scaffold which incorporated bioactive phyto-compounds is a promising potential strategy for bone tissue engineering and regeneration in patients with challenging SAON.

中文翻译：

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掺入成骨性植物分子苦瓜素的多孔复合支架可促进家兔骨坏死骨的骨骼再生

类固醇相关的骨坏死（SAON）通常需要在早期进行手术核心减压（CD）来去除坏死骨，以便在需要植骨以填补骨缺损并避免随后的关节塌陷时进行修复。在这项研究中，我们开发了一种与icariin结合的生物活性复合支架，icariin是一种独特的植物分子，可以在建立的SAON兔模型中提供手术CD后提供结构和机械支持，并促进骨再生填充到骨缺损中。一种创新的低温3D打印技术被用于制造聚（乳酸-共-乙醇酸）/β-磷酸钙/烟碱（PLGA / TCP / Icariin，PTI）支架。在体外测试了PTI支架的细胞相容性和PTI支架的成骨特性进行了评估在体内在SAON兔模型。我们的结果表明，制造的PTI支架具有精心设计的仿生结构，该结构经过精确印刷，可提供增强的机械支撑和稳定的icariin从支架释放的效果，以实现骨骼再生。此外，我们的体内研究表明，与PLGA / TCP（PT）支架相比，PTI支架可以增强SAON兔模型植入区域内新骨组织的机械性能并改善其血管生成。体外使用MC3T3-E1细胞研究了潜在的成骨机制并揭示了icariin可以促进MC3T3-E1细胞向内生长到PTI支架中，并调节成骨细胞的分化。与PT支架相比，PTI支架表现出优异的生物降解性，生物相容性和成骨能力。总之，结合了生物活性植物化合物的PTI复合支架是具有挑战性SAON患者的骨组织工程和再生的有前途的潜在策略。