PMID- 31632013 OWN - NLM STAT- MEDLINE DCOM- 20191213 LR - 20231014 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 14 DP - 2019 TI - Nano-Hydroxyapatite Coating Promotes Porous Calcium Phosphate Ceramic-Induced Osteogenesis Via BMP/Smad Signaling Pathway. PG - 7987-8000 LID - 10.2147/IJN.S216182 [doi] AB - BACKGROUND: The hierarchical porous structure and surface topography of calcium phosphate (CaP) bioceramics have a crucial impact on their osteoinductivity. PURPOSE: To fabricate a biomimetic bone graft with an interconnected porous structure analogous to that of trabecular bone and a bioactive nanostructured surface with excellent osteoinductive potential. MATERIALS AND METHODS: A biphasic CaP (BCP) substrate with highly porous structure was fabricated by an improved sponge replication method. Surface modification was performed by uniformly depositing a hydroxyapatite (HA) nanoparticle layer to create nHA-coated BCP scaffolds. The effects of these scaffolds on osteogenic differentiation of murine bone marrow-derived stem cells (BMSCs) were investigated in vitro, and their osteoinductivity was further assessed in vivo. RESULTS: The BCP and nHA-coated BCP scaffolds had similar trabecular bone-like architectures but different surface structures, with mean grain sizes of ~55 nm and ~1 mum, respectively. Compared with the BCP substrate, the nHA-coated BCP scaffolds favored cell adhesion and promoted osteogenic differentiation of BMSCs, as evidenced by upregulated expression of osteogenic genes, enhanced alkaline phosphatase activity, and increased osteocalcin production. This could be attributed to activation of the BMP/Smad signaling pathway, as significantly higher expression levels of BMPRI, Smad1, Smad4, and Smad5 were observed in the nHA-coated BCP group. The nHA-coated BCP scaffold not only maintained scaffold integrity but also induced ectopic bone formation when implanted into rabbit dorsal muscle in vivo for 90 days, whereas the BCP substrate underwent marked biodegradation that led to severe inflammation with no sign of osteogenesis. CONCLUSION: The present study demonstrates the potential of this biomimetic bone graft with a trabecular framework and nanotopography for use in orthopedic applications. CI - (c) 2019 Wang et al. FAU - Wang, Jing AU - Wang J AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Wang, Menglu AU - Wang M AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Chen, Fuying AU - Chen F AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Wei, Yihang AU - Wei Y AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Chen, Xuening AU - Chen X AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Zhou, Yong AU - Zhou Y AD - Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, People's Republic of China. FAU - Yang, Xiao AU - Yang X AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Zhu, Xiangdong AU - Zhu X AUID- ORCID: 0000-0002-3818-7419 AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. FAU - Tu, Chongqi AU - Tu C AUID- ORCID: 0000-0002-4576-4712 AD - Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, People's Republic of China. FAU - Zhang, Xingdong AU - Zhang X AD - National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China. LA - eng PT - Journal Article DEP - 20191003 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Calcium Phosphates) RN - 0 (Coated Materials, Biocompatible) RN - 0 (Smad Proteins) RN - 91D9GV0Z28 (Durapatite) RN - 97Z1WI3NDX (calcium phosphate) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/metabolism MH - Animals MH - Biomimetic Materials/pharmacology MH - Bone Morphogenetic Proteins/*metabolism MH - Calcium Phosphates/*pharmacology MH - Cell Adhesion/drug effects MH - Cell Differentiation/drug effects MH - Cell Shape/drug effects MH - Ceramics/*pharmacology MH - Choristoma/pathology MH - Coated Materials, Biocompatible/*pharmacology MH - Durapatite/chemistry/*pharmacology MH - Gene Expression Regulation/drug effects MH - Male MH - Mesenchymal Stem Cells/cytology/drug effects/enzymology/ultrastructure MH - Mice MH - Nanoparticles/*chemistry/ultrastructure MH - Osteogenesis/*drug effects/genetics MH - Porosity MH - Rabbits MH - Signal Transduction/drug effects MH - Smad Proteins/*metabolism MH - Tissue Scaffolds/chemistry PMC - PMC6781424 OTO - NOTNLM OT - MSCs OT - calcium phosphate ceramics OT - nano-hydroxyapatite OT - osteoblastic differentiation OT - osteoinduction OT - porous scaffolds COIS- The authors report no conflicts of interest in this work. EDAT- 2019/10/22 06:00 MHDA- 2019/12/18 06:00 PMCR- 2019/10/03 CRDT- 2019/10/22 06:00 PHST- 2019/05/17 00:00 [received] PHST- 2019/09/17 00:00 [accepted] PHST- 2019/10/22 06:00 [entrez] PHST- 2019/10/22 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/10/03 00:00 [pmc-release] AID - 216182 [pii] AID - 10.2147/IJN.S216182 [doi] PST - epublish SO - Int J Nanomedicine. 2019 Oct 3;14:7987-8000. doi: 10.2147/IJN.S216182. eCollection 2019.