Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits

• Published in: Biomaterials 2018-01, Vol.153, p.1-13
• Main Authors: Lai, Yuxiao, Cao, Huijuan, Wang, Xinluan, Chen, Shukui, Zhang, Ming, Wang, Nan, Yao, Zhihong, Dai, Yi, Xie, Xinhui, Zhang, Peng, Yao, Xinsheng, Qin, Ling
• Format: Article
• Language: English
• Subjects: 3D printing; Animals; Biocompatible Materials; Biomimetic Materials; Bone and Bones - metabolism; Bone regeneration; Bone Regeneration - drug effects; Calcium Phosphates - chemistry; Calcium Phosphates - metabolism; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cell Line; Cell Survival - drug effects; Drug Liberation; Flavonoids - administration & dosage; Flavonoids - chemistry; Flavonoids - therapeutic use; Male; Mechanical Phenomena - drug effects; Osteogenesis; Osteonecrosis - drug therapy; Osteonecrosis - physiopathology; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Porosity; Porous scaffold; Printing, Three-Dimensional; Rabbits; Steroid-associated osteonecrosis(SAON); Steroids - metabolism; Tissue Scaffolds - chemistry
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2017.10.025

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. An innovative bioactive composite scaffold (PLGA/TCP/Icariin, PTI) with a well-designed biomimic structure has been successfully developed by low-temperature 3D printing technology. PTI scaffold shows distinct osteogenetic and angiogenetic activity and provides suitable mechanical support to enhance bone regeneration for the cure of SAON. [Display omitted]