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A micro/nano-biomimetic coating on titanium orchestrates osteo/angio-genesis and osteoimmunomodulation for advanced
Long Bai1, Peiru Chen2, Ya Zhao3
1Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China; Laboratory of Biomaterial Surfaces & Interfaces, Institute of New Carbon Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, China; School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, Australia; Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China; Australia-China Centre for Tissue Engineering and Regenerative Medicine, Queensland University of Technology, Brisbane, Australia; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Shanghai, 200237, China.
Abstract:
Osseointegration is a sophisticated bone and implant healing process comprising of initial hematoma formation, immediate osteoimmunomodulation, angiogenesis, and osteogenesis. To fulfill rapid and satisfying osseointegration, this study developed a biomimetic implant coating that could confer the intraosseous implants a systematical regulation of the participatory processes. Herein, we shaped dissimilar nano-scale (NS) to form highly biomimetic structures of natural extracellular matrix (ECM) of the host bone and bone healing hematoma with micro/nano-scale (MNS) titania fiber-like network on the surface of titanium (Ti) implants. In vitro experiments revealed that the MNS not only facilitated osteogenic and angiogenic differentiation of bone marrow stromal cells (BMSCs) and endothelial cells, respectively, but also suppressed M1 macrophages (MΦs), whereas, stimulated pro-healing M2 phenotype. Notably, BMSCs on MNS surfaces enabled a significant immunomodulatory effect on MΦs resulting in the downregulation of inflammation-related cell signaling pathways. The favorable osteoimmune microenvironment manipulated by MNS further facilitated osteo-/angio-genesis via the crosstalk of multi-signaling pathways. In vivo evaluation mirrored the aforementioned results, and depicted that MNS induced ameliorative osseointegration when compared with the NS as well as the pristine Ti implant. The study demonstrated the modulatory effect of the multifaceted biomimetic structure on spatiotemporal regulation of the participatory processes during osseointegration.
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